Cell surface interactions at the vascular wall (Homo sapiens)

From WikiPathways

Revision as of 14:07, 8 May 2014 by Anwesha (Talk | contribs)
Jump to: navigation, search
12, 32, 66, 69, 72...20, 57, 66, 7149, 733526, 47, 48, 8024, 66, 7568425, 39, 4266, 7022, 28, 8859, 668353, 7718110, 6722, 605, 30, 7876328, 88453117, 27, 368, 859, 14, 16, 38, 436426621, 541115, 22466366, 79722, 6022, 6513, 583633, 40, 56, 6615, 294166, 878623, 61, 6919, 474, 55836437, 5182SLC7A9SLC3A2 heterodimer SLC7A7SLC3A2 heterodimer SLC7A8SLC3A2 heterodimer FCERIG dimer SLC7A8SLC3A2 heterodimer CD98hc complex Integrin alpha5beta1Fibronectin P-selectin bound to its ligand SLC7A5SLC3A2 heterodimer Integrin alphaVbeta3PECAM-1 Tie2/Ang1 dimer pTie2Ang-1 VLA-4 JAM-B homodimer SLC7A11SLC3A2 heterodimer PECAM-1PLC gamma1 complex Integrin alphaVbeta3 PI3K-regulatory subunit CD48 bound to CD244 GP VI FceRI gamma dimer Selectin Complex of Tie2Ang-1 Basigin homodimer PECAM-1SHP-2 complex JAM-C homodimer PECAM-1 bound to CD177 Integrin alpha6beta1 Integrin alphaLbeta2 Integrin alpha5beta1 MCT1 homodimer PECAM-1SHP-1 complex activated protein C Complex of Tie2Ang-1 PI3K-catalytic subunit VLA-4 Mannose-carrying cell recognition molecules VLA-4 JAM-B Phosphorylated Tie2 in Tie2/Akt dimer Integrin alphaMbeta2 FN1 dimer BasiginMMP1 CyP60 complexed with Basigin GPVIFceRI gammaFYNLYN Integrin alphaXbeta2 Sodium/potassium-transporting ATPase beta subunit p21 RASGDP CEACAM heterodimer Integrin alphaMbeta2 Integrin alpha5beta1 Basigin bound to integrins Integrin alpha6beta1 Mannose-carrying cell recognition molecules PECAM-1PECAM-1 CXADR bound to JAML Caveolin-1 bound to Basigin activated thrombin Basigin bound to MCTs p21 RAS pTie2Ang-1 Basigin-binding integrins LFA-1JAM-A BasiginMannose-carrying cell recognition molecules GP VI FceRI gamma dimer LDL LDL Tie2 and Dok-2 complex GPVIFceRI gammaFYNLYN cytosolIntegrin alpha3beta1 Integrin alpha3beta1 Basigin-binding integrins SLC7A6SLC3A2 heterodimer p21 RAS Golgi membraneSodium/potassium-transporting ATPase beta subunit SLC7A9SLC3A2 heterodimer TREM-1 bound to its ligand pTie2Ang-1 PI3K-regulatory subunit SLC7A7SLC3A2 heterodimer p85 bound to Tie2 plasma membranepTie2Ang-1 Integrin alphaXbeta2 PI3K Neutrophil CEACAMs affecting integrin binding to fibronectin OLR1 bound to oxidized LDL Integrin alphaXbeta2AMICA1 MCT3 homodimer Integrin alphaMbeta2JAM3 Tie2 and Grb14 complex activated thrombinthrombomodulin CD58 bound to CD2 Tie2Grb7 complex pTie2SHC1 complex FCERIG dimer BasiginCD98hc complex Complex of Tie2Ang2 Integrin alphaLbeta2 PI3K pTie2Ang-1 Grb2 bound to Tie2 JAM-B bound to JAM-C MCT4 homodimer CD84 dimer MERTK bound to its ligand Grb2 bound to Tie2 CD98hc complex JAM-A Homodimer FN1 dimer SLC7A10SLC3A2 heterodimer p21 RASGTP pTie2Ang-1 Tie2 and Ang4 complex GPVIFceRI gammaFYNLYNCollagen type I Basigin bound to CyPA pTie2Ang-1 pTie2Ang-1 protein C Basigin bound to CD43 SLC7A11SLC3A2 heterodimer PI3K-catalytic subunit pTie2Ang-1 SOS-1 bound to Tie2Grb2 SLC7A5SLC3A2 heterodimer PECAM-1SHIP1 complex Golgi lumenpTie2Ang-1 Integrin alphaVbeta3 SLC7A10SLC3A2 heterodimer Monocarboxylate Transporter Homodimers p-PECAM1p-PECAM1 CD47-binding SIRPs pTie2 and SHP2 complex CD47 bound to its ligand SLC7A6SLC3A2 heterodimer MERTK ligands Grb2 bound to Tie2PIK3R2 Integrin alphaLbeta2 p21 RASGDPCEACAM1 Integrin alphaXbeta2AMICA1SLC7A10 PTPN11 ITGB2 GRB2-1 SPN 8xCbxE-3D-PROCITGAX BSG Integrin alpha5beta1ITGAM SHC1 TEK 11xCbxE-GAS6CD84JAM2Mannose-carrying cell recognition moleculesBasigin homodimerCHOL MERTK Mn2+TEK JAM-A HomodimerPROCPECAM1activated thrombinthrombomodulinBasigin bound to CD43OLR1 bound to oxidized LDLBasiginMMP1SPNp-5Y,S1119-TEK PPIA Heparan SulphateCD244 CD47 bound to its ligandJAM-C homodimerITGA4ATP1B3 ANGPT1 p-5Y,S1119-TEK TREM-1 bound to its ligandGTP p-5Y,S1119-TEK ITGB3 BasiginMannose-carrying cell recognition moleculesSOS-1 bound to Tie2Grb2PIK3CB SELL Ligand to TREM-1 on the platelet membraneANGPT1 SLC3A2 ITGB1 MMP1CHEST KRASp-Y663,Y686-PECAM1TREM1 BSG SLC16A3ITGA3TEK SLC7A11 ATP1B1 GDPthrombin heavy chain ITGB1 CD244PPIL2p-5Y,S1119-TEK Mn2+ p-Y663,Y686-PECAM1CXADRANGPT1 PECAM-1 bound to CD177JAM3 HRASADPSELP PIK3R1 KRASCEACAM8 SIRPG p21 RASGTPP-selectin bound to its ligandPhosphorylated Tie2 in Tie2/Akt dimerPECAM1L1CAM ANGPT4CD48 bound to CD244SLC7A5 Ca2+ GRB7TREM1SLC7A11 PLCG1ANGPT1 ATP1B3 Integrin alphaXbeta2SLC7A6 ESAM PTPN11 CD48 APOBPECAM-1PECAM-1BSG SELE PECAM18xCbxE-3D-PROCITGAL CAV1PPIL2 Tie2Grb7 complexSLC7A5 PROCBSG PECAM-1SHP-1 complexL1CAM ITGA5PECAM-1SHIP1 complexSLC16A8 JAM-B bound to JAM-CCD98hc complexBSG MAG CD2 ATPJAM3 ANGPT1 AMICA1GDP THBDTie2 and Grb14 complexIntegrin alphaVbeta3Complex of Tie2Ang-1PROCp-5Y,S1119-TEK Integrin alphaMbeta2JAM3JAM3 LYNATP1B2 SLC7A8 TEK SLC3A2 pTie2 and SHP2 complexNRAS CEACAM6 PIK3CB TAGs Neutrophil CEACAMs affecting integrin binding to fibronectinCD177 ITGB3 CD84 dimerTie2 and Ang4 complexSIRPA CXADR bound to JAMLGP6 Ca2+ Integrin alphaMbeta2pTie2Ang-1ADPVLA-4p-5Y,S1119-TEK PECAM-1SHP-2 complexBSGp-Y663,Y686-PECAM1PLCG1F11RBSG ANGPT1 Src family tyrosine kinases LYNITGA5CD58ATPSLC7A9 F11R FCER1G p-Y663,Y686-PECAM1ANGPT1 ATP1B1 PIK3CA GP6 p-Y663,Y686-PECAM1FYNBasigin bound to CyPAMMP1AMICA1 GRB7 GPVIFceRI gammaFYNLYNCollagen type IANGPT1 FCER1G OLR1Basigin bound to MCTsSOS1 GRB14 p-5Y,S1119-TEK Integrin alphaVbeta3PECAM-1SLC7A10 Tie2 and Dok-2 complexJAM-B homodimerMERTKVLA-4 JAM-BANGPT2ANGPT2 CHEST SLC7A7 ITGB1 ITGA3PL MAG APOBGRB14MERTK ligandsCaveolin-1 bound to BasiginSELPLGITGAVTie2/Ang1 dimerBasigin-binding integrinsTEKBasigin bound to integrinsthrombin light chain Complex of Tie2Ang2DOK2ITGAVPIK3CA LDLPIK3R1 pTie2SHC1 complexITGB1 PIK3R2 SLC7A9 CD58 bound to CD2p-5Y,S1119-TEK ITGAX JAM2 p-Y663,Y686-PECAM1JAM3 SLC16A1 BSG MERTK bound to its ligandINPP5DSelectinITGAM ITGA6GPVIFceRI gammaFYNLYNITGB2 FN1BSG protein CTAGs ANGPT1 Monocarboxylate Transporter Set JAM3Collagen type I fibrilF11R BSGFN1SHC1p-PECAM1p-PECAM1SLC7A7 Integrin alpha5beta1FibronectinPECAM1SPNp85 bound to Tie2CD2PPIAOLR1 p-5Y,S1119-TEK PTPN6 CD48GTP11xCbxE-PROS1 ANGPT1 ITGAL ANGPT1 DOK2 ANGPT4 SELPLG BasiginCD98hc complexactivated protein CSLC7A6 ITGB1 JAM2 ATP1B2 PTPN6FYNPL CyP60 complexed with BasiginINPP5D CD177ITGB2 BSG FN1 dimerITGA4ITGA6CEACAM heterodimerANGPT1 NRAS ITGB2 JAM2GRB2-1SLC7A8 CD58CD47 p-5Y,S1119-TEK CD84 BSG CXADR Platelet Factor 4LFA-1JAM-ACD47-binding SIRPsGRB2-1 PTPN11ITGB2 ITGB2 CAV1 SOS1PECAM-1PLC gamma1 complexCHOL PI3KHRASITGB1 CD47ANGPT1276844, 51, 8944, 50, 892762863744, 50, 89627444, 51, 8944, 893444, 51, 8944, 895274


Description

Leukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are required for leukocytes to withstand local flow at the vessel wall is a multistep process mediated by different adhesion molecules. Platelets adhered to injured vessel walls form strong adhesive substrates for leukocytes. For instance, the initial tethering and rolling of leukocytes over the site of injury are mediated by reversible binding of selectins to their cognate cell-surface glycoconjugates.

Endothelial cells are tightly connected through various proteins, which regulate the organization of the junctional complex and bind to cytoskeletal proteins or cytoplasmic interaction partners that allow the transfer of intracellular signals. An important role for these junctional proteins in governing the transendothelial migration of leukocytes under normal or inflammatory conditions has been established.<p>

This pathway describes some of the key interactions that assist in the process of platelet and leukocyte interaction with the endothelium, in response to injury.

Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=202733</div>

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Jones N, Dumont DJ.; ''The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R.''; PubMed Europe PMC Scholia
  2. Huang H, Cruz F, Bazzoni G.; ''Junctional adhesion molecule-A regulates cell migration and resistance to shear stress.''; PubMed Europe PMC Scholia
  3. Hafizi S, Dahlbäck B.; ''Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases.''; PubMed Europe PMC Scholia
  4. Yan Q, Malashkevich VN, Fedorov A, Fedorov E, Cao E, Lary JW, Cole JL, Nathenson SG, Almo SC.; ''Structure of CD84 provides insight into SLAM family function.''; PubMed Europe PMC Scholia
  5. Hua CT, Gamble JR, Vadas MA, Jackson DE.; ''Recruitment and activation of SHP-1 protein-tyrosine phosphatase by human platelet endothelial cell adhesion molecule-1 (PECAM-1). Identification of immunoreceptor tyrosine-based inhibitory motif-like binding motifs and substrates.''; PubMed Europe PMC Scholia
  6. Esmon CT.; ''The roles of protein C and thrombomodulin in the regulation of blood coagulation.''; PubMed Europe PMC Scholia
  7. Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R.; ''MIF signal transduction initiated by binding to CD74.''; PubMed Europe PMC Scholia
  8. Guo H, Li R, Zucker S, Toole BP.; ''EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface.''; PubMed Europe PMC Scholia
  9. Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP.; ''CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression.''; PubMed Europe PMC Scholia
  10. Wanaguru M, Crosnier C, Johnson S, Rayner JC, Wright GJ.; ''Biochemical analysis of the Plasmodium falciparum erythrocyte-binding antigen-175 (EBA175)-glycophorin-A interaction: implications for vaccine design.''; PubMed Europe PMC Scholia
  11. Litvinov SV, Balzar M, Winter MJ, Bakker HA, Briaire-de Bruijn IH, Prins F, Fleuren GJ, Warnaar SO.; ''Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins.''; PubMed Europe PMC Scholia
  12. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM.; ''An antagonist decoy receptor and a death domain-containing receptor for TRAIL.''; PubMed Europe PMC Scholia
  13. Kontos CD, Stauffer TP, Yang WP, York JD, Huang L, Blanar MA, Meyer T, Peters KG.; ''Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.''; PubMed Europe PMC Scholia
  14. Messmer B, Eissmann P, Stark S, Watzl C.; ''CD48 stimulation by 2B4 (CD244)-expressing targets activates human NK cells.''; PubMed Europe PMC Scholia
  15. Kalinowska A, Losy J.; ''PECAM-1, a key player in neuroinflammation.''; PubMed Europe PMC Scholia
  16. Xu Y, Yu Q.; ''Angiopoietin-1, unlike angiopoietin-2, is incorporated into the extracellular matrix via its linker peptide region.''; PubMed Europe PMC Scholia
  17. Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD.; ''Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31.''; PubMed Europe PMC Scholia
  18. Yoshida S, Shibata M, Yamamoto S, Hagihara M, Asai N, Takahashi M, Mizutani S, Muramatsu T, Kadomatsu K.; ''Homo-oligomer formation by basigin, an immunoglobulin superfamily member, via its N-terminal immunoglobulin domain.''; PubMed Europe PMC Scholia
  19. Trzpis M, McLaughlin PM, de Leij LM, Harmsen MC.; ''Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule.''; PubMed Europe PMC Scholia
  20. Huang L, Turck CW, Rao P, Peters KG.; ''GRB2 and SH-PTP2: potentially important endothelial signaling molecules downstream of the TEK/TIE2 receptor tyrosine kinase.''; PubMed Europe PMC Scholia
  21. Blois SM, Sulkowski G, Tirado-González I, Warren J, Freitag N, Klapp BF, Rifkin D, Fuss I, Strober W, Dveksler GS.; ''Pregnancy-specific glycoprotein 1 (PSG1) activates TGF-β and prevents dextran sodium sulfate (DSS)-induced colitis in mice.''; PubMed Europe PMC Scholia
  22. Lisboa FA, Warren J, Sulkowski G, Aparicio M, David G, Zudaire E, Dveksler GS.; ''Pregnancy-specific glycoprotein 1 induces endothelial tubulogenesis through interaction with cell surface proteoglycans.''; PubMed Europe PMC Scholia
  23. Hafizi S, Dahlbäck B.; ''Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily.''; PubMed Europe PMC Scholia
  24. Bradfield PF, Scheiermann C, Nourshargh S, Ody C, Luscinskas FW, Rainger GE, Nash GB, Miljkovic-Licina M, Aurrand-Lions M, Imhof BA.; ''JAM-C regulates unidirectional monocyte transendothelial migration in inflammation.''; PubMed Europe PMC Scholia
  25. Haselmayer P, Grosse-Hovest L, von Landenberg P, Schild H, Radsak MP.; ''TREM-1 ligand expression on platelets enhances neutrophil activation.''; PubMed Europe PMC Scholia
  26. Jackson SP, Mistry N, Yuan Y.; ''Platelets and the injured vessel wall-- "rolling into action": focus on glycoprotein Ib/V/IX and the platelet cytoskeleton.''; PubMed Europe PMC Scholia
  27. Farias E, Lu M, Li X, Schnapp LM.; ''Integrin alpha8beta1-fibronectin interactions promote cell survival via PI3 kinase pathway.''; PubMed Europe PMC Scholia
  28. Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO.; ''Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule.''; PubMed Europe PMC Scholia
  29. Mayer DC, Cofie J, Jiang L, Hartl DL, Tracy E, Kabat J, Mendoza LH, Miller LH.; ''Glycophorin B is the erythrocyte receptor of Plasmodium falciparum erythrocyte-binding ligand, EBL-1.''; PubMed Europe PMC Scholia
  30. Ordonez C, Zhai AB, Camacho-Leal P, Demarte L, Fan MM, Stanners CP.; ''GPI-anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin alpha5beta1-fibronectin interaction.''; PubMed Europe PMC Scholia
  31. Melchers F, Karasuyama H, Haasner D, Bauer S, Kudo A, Sakaguchi N, Jameson B, Rolink A.; ''The surrogate light chain in B-cell development.''; PubMed Europe PMC Scholia
  32. Tang W, Hemler ME.; ''Caveolin-1 regulates matrix metalloproteinases-1 induction and CD147/EMMPRIN cell surface clustering.''; PubMed Europe PMC Scholia
  33. Bradfield PF, Nourshargh S, Aurrand-Lions M, Imhof BA.; ''JAM family and related proteins in leukocyte migration (Vestweber series).''; PubMed Europe PMC Scholia
  34. Weber C, Fraemohs L, Dejana E.; ''The role of junctional adhesion molecules in vascular inflammation.''; PubMed Europe PMC Scholia
  35. Yurchenko V, Zybarth G, O'Connor M, Dai WW, Franchin G, Hao T, Guo H, Hung HC, Toole B, Gallay P, Sherry B, Bukrinsky M.; ''Active site residues of cyclophilin A are crucial for its signaling activity via CD147.''; PubMed Europe PMC Scholia
  36. Berditchevski F, Chang S, Bodorova J, Hemler ME.; ''Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6.''; PubMed Europe PMC Scholia
  37. Foster DC, Sprecher CA, Holly RD, Gambee JE, Walker KM, Kumar AA.; ''Endoproteolytic processing of the dibasic cleavage site in the human protein C precursor in transfected mammalian cells: effects of sequence alterations on efficiency of cleavage.''; PubMed Europe PMC Scholia
  38. Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y.; ''CATs and HATs: the SLC7 family of amino acid transporters.''; PubMed Europe PMC Scholia
  39. Ostermann G, Weber KS, Zernecke A, Schröder A, Weber C.; ''JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes.''; PubMed Europe PMC Scholia
  40. Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD.; ''Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning.''; PubMed Europe PMC Scholia
  41. Woodfin A, Reichel CA, Khandoga A, Corada M, Voisin MB, Scheiermann C, Haskard DO, Dejana E, Krombach F, Nourshargh S.; ''JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration.''; PubMed Europe PMC Scholia
  42. McMullen BA, Fujikawa K, Kisiel W.; ''The occurrence of beta-hydroxyaspartic acid in the vitamin K-dependent blood coagulation zymogens.''; PubMed Europe PMC Scholia
  43. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD.; ''Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis.''; PubMed Europe PMC Scholia
  44. Furie B, Furie BC.; ''The molecular basis of platelet and endothelial cell interaction with neutrophils and monocytes: role of P-selectin and the P-selectin ligand, PSGL-1.''; PubMed Europe PMC Scholia
  45. Jones N, Dumont DJ.; ''Tek/Tie2 signaling: new and old partners.''; PubMed Europe PMC Scholia
  46. Valenzuela DM, Griffiths JA, Rojas J, Aldrich TH, Jones PF, Zhou H, McClain J, Copeland NG, Gilbert DJ, Jenkins NA, Huang T, Papadopoulos N, Maisonpierre PC, Davis S, Yancopoulos GD.; ''Angiopoietins 3 and 4: diverging gene counterparts in mice and humans.''; PubMed Europe PMC Scholia
  47. Tangye SG, Phillips JH, Lanier LL.; ''The CD2-subset of the Ig superfamily of cell surface molecules: receptor-ligand pairs expressed by NK cells and other immune cells.''; PubMed Europe PMC Scholia
  48. Seitz HM, Camenisch TD, Lemke G, Earp HS, Matsushima GK.; ''Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells.''; PubMed Europe PMC Scholia
  49. Wilson MC, Meredith D, Halestrap AP.; ''Fluorescence resonance energy transfer studies on the interaction between the lactate transporter MCT1 and CD147 provide information on the topology and stoichiometry of the complex in situ.''; PubMed Europe PMC Scholia
  50. Maier AG, Duraisingh MT, Reeder JC, Patel SS, Kazura JW, Zimmerman PA, Cowman AF.; ''Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations.''; PubMed Europe PMC Scholia
  51. McDonald KJ, Cameron AJ, Allen JM, Jardine AG.; ''Expression of Fc alpha/mu receptor by human mesangial cells: a candidate receptor for immune complex deposition in IgA nephropathy.''; PubMed Europe PMC Scholia
  52. da Costa Martins P, García-Vallejo JJ, van Thienen JV, Fernandez-Borja M, van Gils JM, Beckers C, Horrevoets AJ, Hordijk PL, Zwaginga JJ.; ''P-selectin glycoprotein ligand-1 is expressed on endothelial cells and mediates monocyte adhesion to activated endothelium.''; PubMed Europe PMC Scholia
  53. Newton JP, Buckley CD, Jones EY, Simmons DL.; ''Residues on both faces of the first immunoglobulin fold contribute to homophilic binding sites of PECAM-1/CD31.''; PubMed Europe PMC Scholia
  54. Loughna S, Sato TN.; ''Angiopoietin and Tie signaling pathways in vascular development.''; PubMed Europe PMC Scholia
  55. Wilkins AL, Yang W, Yang JJ.; ''Structural biology of the cell adhesion protein CD2: from molecular recognition to protein folding and design.''; PubMed Europe PMC Scholia
  56. Langer HF, Daub K, Braun G, Schönberger T, May AE, Schaller M, Stein GM, Stellos K, Bueltmann A, Siegel-Axel D, Wendel HP, Aebert H, Roecken M, Seizer P, Santoso S, Wesselborg S, Brossart P, Gawaz M.; ''Platelets recruit human dendritic cells via Mac-1/JAM-C interaction and modulate dendritic cell function in vitro.''; PubMed Europe PMC Scholia
  57. Tsuji M, Ezumi Y, Arai M, Takayama H.; ''A novel association of Fc receptor gamma-chain with glycoprotein VI and their co-expression as a collagen receptor in human platelets.''; PubMed Europe PMC Scholia
  58. Newton JP, Hunter AP, Simmons DL, Buckley CD, Harvey DJ.; ''CD31 (PECAM-1) exists as a dimer and is heavily N-glycosylated.''; PubMed Europe PMC Scholia
  59. Xu D, Hemler ME.; ''Metabolic activation-related CD147-CD98 complex.''; PubMed Europe PMC Scholia
  60. Khunkaewla P, Schiller HB, Paster W, Leksa V, Cermák L, Andera L, Horejsí V, Stockinger H.; ''LFA-1-mediated leukocyte adhesion regulated by interaction of CD43 with LFA-1 and CD147.''; PubMed Europe PMC Scholia
  61. Han DC, Shen TL, Guan JL.; ''The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions.''; PubMed Europe PMC Scholia
  62. Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D, Imhof BA.; ''CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium.''; PubMed Europe PMC Scholia
  63. Schröder AK, Uciechowski P, Fleischer D, Rink L.; ''Crosslinking of CD66B on peripheral blood neutrophils mediates the release of interleukin-8 from intracellular storage.''; PubMed Europe PMC Scholia
  64. Bayas MV, Kearney A, Avramovic A, van der Merwe PA, Leckband DE.; ''Impact of salt bridges on the equilibrium binding and adhesion of human CD2 and CD58.''; PubMed Europe PMC Scholia
  65. Ward NL, Dumont DJ.; ''The angiopoietins and Tie2/Tek: adding to the complexity of cardiovascular development.''; PubMed Europe PMC Scholia
  66. Brakebusch C, Fässler R.; ''beta 1 integrin function in vivo: adhesion, migration and more.''; PubMed Europe PMC Scholia
  67. Ostermann G, Fraemohs L, Baltus T, Schober A, Lietz M, Zernecke A, Liehn EA, Weber C.; ''Involvement of JAM-A in mononuclear cell recruitment on inflamed or atherosclerotic endothelium: inhibition by soluble JAM-A.''; PubMed Europe PMC Scholia
  68. Master Z, Jones N, Tran J, Jones J, Kerbel RS, Dumont DJ.; ''Dok-R plays a pivotal role in angiopoietin-1-dependent cell migration through recruitment and activation of Pak.''; PubMed Europe PMC Scholia
  69. Barton WA, Tzvetkova D, Nikolov DB.; ''Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition.''; PubMed Europe PMC Scholia
  70. Martin M, Romero X, de la Fuente MA, Tovar V, Zapater N, Esplugues E, Esplugues E, Pizcueta P, Bosch J, Engel P.; ''CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like domain 1.''; PubMed Europe PMC Scholia
  71. Neumann S, Hasenauer J, Pollak N, Scheurich P.; ''Dominant negative effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 4 on TRAIL receptor 1 signaling by formation of heteromeric complexes.''; PubMed Europe PMC Scholia
  72. Deora AA, Philp N, Hu J, Bok D, Rodriguez-Boulan E.; ''Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia.''; PubMed Europe PMC Scholia
  73. DiScipio RG, Davie EW.; ''Characterization of protein S, a gamma-carboxyglutamic acid containing protein from bovine and human plasma.''; PubMed Europe PMC Scholia
  74. Sachs UJ, Andrei-Selmer CL, Maniar A, Weiss T, Paddock C, Orlova VV, Choi EY, Newman PJ, Preissner KT, Chavakis T, Santoso S.; ''The neutrophil-specific antigen CD177 is a counter-receptor for platelet endothelial cell adhesion molecule-1 (CD31).''; PubMed Europe PMC Scholia
  75. Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J.; ''The structural basis of the activation of Ras by Sos.''; PubMed Europe PMC Scholia
  76. Moriwaki H, Kume N, Sawamura T, Aoyama T, Hoshikawa H, Ochi H, Nishi E, Masaki T, Kita T.; ''Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low density lipoprotein.''; PubMed Europe PMC Scholia
  77. Pushkarsky T, Yurchenko V, Vanpouille C, Brichacek B, Vaisman I, Hatakeyama S, Nakayama KI, Sherry B, Bukrinsky MI.; ''Cell surface expression of CD147/EMMPRIN is regulated by cyclophilin 60.''; PubMed Europe PMC Scholia
  78. Xie Q, Matsunaga S, Niimi S, Ogawa S, Tokuyasu K, Sakakibara Y, Machida S.; ''Human lectin-like oxidized low-density lipoprotein receptor-1 functions as a dimer in living cells.''; PubMed Europe PMC Scholia
  79. Cartron JP, Rahuel C.; ''Human erythrocyte glycophorins: protein and gene structure analyses.''; PubMed Europe PMC Scholia
  80. Merzaban JS, Burdick MM, Gadhoum SZ, Dagia NM, Chu JT, Fuhlbrigge RC, Sackstein R.; ''Analysis of glycoprotein E-selectin ligands on human and mouse marrow cells enriched for hematopoietic stem/progenitor cells.''; PubMed Europe PMC Scholia
  81. Kisiel W.; ''Human plasma protein C: isolation, characterization, and mechanism of activation by alpha-thrombin.''; PubMed Europe PMC Scholia
  82. Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE.; ''Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene.''; PubMed Europe PMC Scholia
  83. Barclay AN, Brown MH.; ''The SIRP family of receptors and immune regulation.''; PubMed Europe PMC Scholia
  84. Audero E, Cascone I, Maniero F, Napione L, Arese M, Lanfrancone L, Bussolino F.; ''Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells.''; PubMed Europe PMC Scholia
  85. Foster D, Davie EW.; ''Characterization of a cDNA coding for human protein C.''; PubMed Europe PMC Scholia
  86. Peters KG, Kontos CD, Lin PC, Wong AL, Rao P, Huang L, Dewhirst MW, Sankar S.; ''Functional significance of Tie2 signaling in the adult vasculature.''; PubMed Europe PMC Scholia
  87. Buckley CD, Doyonnas R, Newton JP, Blystone SD, Brown EJ, Watt SM, Simmons DL.; ''Identification of alpha v beta 3 as a heterotypic ligand for CD31/PECAM-1.''; PubMed Europe PMC Scholia
  88. Becker BF, Heindl B, Kupatt C, Zahler S.; ''Endothelial function and hemostasis.''; PubMed Europe PMC Scholia
  89. Ludwig RJ, Zollner TM, Santoso S, Hardt K, Gille J, Baatz H, Johann PS, Pfeffer J, Radeke HH, Schön MP, Kaufmann R, Boehncke WH, Podda M.; ''Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation.''; PubMed Europe PMC Scholia
  90. Jones N, Master Z, Jones J, Bouchard D, Gunji Y, Sasaki H, Daly R, Alitalo K, Dumont DJ.; ''Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration.''; PubMed Europe PMC Scholia
  91. Mandicourt G, Iden S, Ebnet K, Aurrand-Lions M, Imhof BA.; ''JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration.''; PubMed Europe PMC Scholia
  92. Moore KL, Eaton SF, Lyons DE, Lichenstein HS, Cummings RD, McEver RP.; ''The P-selectin glycoprotein ligand from human neutrophils displays sialylated, fucosylated, O-linked poly-N-acetyllactosamine.''; PubMed Europe PMC Scholia
  93. Santoso S, Sachs UJ, Kroll H, Linder M, Ruf A, Preissner KT, Chavakis T.; ''The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1.''; PubMed Europe PMC Scholia
  94. Yoshida H, Kondratenko N, Green S, Steinberg D, Quehenberger O.; ''Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor.''; PubMed Europe PMC Scholia
  95. Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T.; ''An endothelial receptor for oxidized low-density lipoprotein.''; PubMed Europe PMC Scholia
  96. Jackson DE, Ward CM, Wang R, Newman PJ.; ''The protein-tyrosine phosphatase SHP-2 binds platelet/endothelial cell adhesion molecule-1 (PECAM-1) and forms a distinct signaling complex during platelet aggregation. Evidence for a mechanistic link between PECAM-1- and integrin-mediated cellular signaling.''; PubMed Europe PMC Scholia
  97. Cicmil M, Thomas JM, Sage T, Barry FA, Leduc M, Bon C, Gibbins JM.; ''Collagen, convulxin, and thrombin stimulate aggregation-independent tyrosine phosphorylation of CD31 in platelets. Evidence for the involvement of Src family kinases.''; PubMed Europe PMC Scholia
  98. Heller M, von der Ohe M, Kleene R, Mohajeri MH, Schachner M.; ''The immunoglobulin-superfamily molecule basigin is a binding protein for oligomannosidic carbohydrates: an anti-idiotypic approach.''; PubMed Europe PMC Scholia
  99. Schober A, Weber C.; ''Mechanisms of monocyte recruitment in vascular repair after injury.''; PubMed Europe PMC Scholia
  100. Cunningham SA, Rodriguez JM, Arrate MP, Tran TM, Brock TA.; ''JAM2 interacts with alpha4beta1. Facilitation by JAM3.''; PubMed Europe PMC Scholia
  101. Graves BJ, Crowther RL, Chandran C, Rumberger JM, Li S, Huang KS, Presky DH, Familletti PC, Wolitzky BA, Burns DK.; ''Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains.''; PubMed Europe PMC Scholia
  102. Bos MP, Grunert F, Belland RJ.; ''Differential recognition of members of the carcinoembryonic antigen family by Opa variants of Neisseria gonorrhoeae.''; PubMed Europe PMC Scholia
  103. Zen K, Liu Y, McCall IC, Wu T, Lee W, Babbin BA, Nusrat A, Parkos CA.; ''Neutrophil migration across tight junctions is mediated by adhesive interactions between epithelial coxsackie and adenovirus receptor and a junctional adhesion molecule-like protein on neutrophils.''; PubMed Europe PMC Scholia
  104. Shi X, Niimi S, Ohtani T, Machida S.; ''Characterization of residues and sequences of the carbohydrate recognition domain required for cell surface localization and ligand binding of human lectin-like oxidized LDL receptor.''; PubMed Europe PMC Scholia
  105. Popp A, Dehio C, Grunert F, Meyer TF, Gray-Owen SD.; ''Molecular analysis of neisserial Opa protein interactions with the CEA family of receptors: identification of determinants contributing to the differential specificities of binding.''; PubMed Europe PMC Scholia
  106. Zhang Z, Morla AO, Vuori K, Bauer JS, Juliano RL, Ruoslahti E.; ''The alpha v beta 1 integrin functions as a fibronectin receptor but does not support fibronectin matrix assembly and cell migration on fibronectin.''; PubMed Europe PMC Scholia
  107. Balzar M, Winter MJ, de Boer CJ, Litvinov SV.; ''The biology of the 17-1A antigen (Ep-CAM).''; PubMed Europe PMC Scholia
  108. Bogdanovic E, Nguyen VP, Dumont DJ.; ''Activation of Tie2 by angiopoietin-1 and angiopoietin-2 results in their release and receptor internalization.''; PubMed Europe PMC Scholia
  109. Fraemohs L, Koenen RR, Ostermann G, Heinemann B, Weber C.; ''The functional interaction of the beta 2 integrin lymphocyte function-associated antigen-1 with junctional adhesion molecule-A is mediated by the I domain.''; PubMed Europe PMC Scholia
  110. da Costa Martins P, van den Berk N, Ulfman LH, Koenderman L, Hordijk PL, Zwaginga JJ.; ''Platelet-monocyte complexes support monocyte adhesion to endothelium by enhancing secondary tethering and cluster formation.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
112591view15:56, 9 October 2020ReactomeTeamReactome version 73
101507view11:37, 1 November 2018ReactomeTeamreactome version 66
101043view21:18, 31 October 2018ReactomeTeamreactome version 65
100574view19:51, 31 October 2018ReactomeTeamreactome version 64
100123view16:37, 31 October 2018ReactomeTeamreactome version 63
99673view15:07, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99268view12:45, 31 October 2018ReactomeTeamreactome version 62
94057view13:54, 16 August 2017ReactomeTeamreactome version 61
93737view13:25, 16 August 2017ReactomeTeamreactome version 61
93686view11:31, 9 August 2017ReactomeTeamreactome version 61
87157view19:14, 18 July 2016MkutmonOntology Term : 'hemostasis pathway' added !
86809view09:27, 11 July 2016ReactomeTeamreactome version 56
83824view13:10, 13 December 2015EgonwMarked heparan sulfate (HS) as a metabolite.
83200view10:21, 18 November 2015ReactomeTeamVersion54
81579view13:07, 21 August 2015ReactomeTeamVersion53
77039view08:33, 17 July 2014ReactomeTeamFixed remaining interactions
76744view12:10, 16 July 2014ReactomeTeamFixed remaining interactions
76069view10:13, 11 June 2014ReactomeTeamRe-fixing comment source
75779view11:29, 10 June 2014ReactomeTeamReactome 48 Update
75129view14:07, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74859view15:22, 2 May 2014EgonwMarked a metabolite as a DataNode type="Metabolite"...
74776view08:51, 30 April 2014ReactomeTeamReactome46
42017view21:50, 4 March 2011MaintBotAutomatic update
39820view05:51, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
11xCbxE-GAS6ProteinQ14393 (Uniprot-TrEMBL)
11xCbxE-PROS1 ProteinP07225 (Uniprot-TrEMBL)
8xCbxE-3D-PROCProteinP04070 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
AMICA1 ProteinQ86YT9 (Uniprot-TrEMBL)
AMICA1ProteinQ86YT9 (Uniprot-TrEMBL)
ANGPT1 ProteinQ15389 (Uniprot-TrEMBL)
ANGPT1ProteinQ15389 (Uniprot-TrEMBL)
ANGPT2 ProteinO15123 (Uniprot-TrEMBL)
ANGPT2ProteinO15123 (Uniprot-TrEMBL)
ANGPT4 ProteinQ9Y264 (Uniprot-TrEMBL)
ANGPT4ProteinQ9Y264 (Uniprot-TrEMBL)
APOBProteinP04114 (Uniprot-TrEMBL)
ATP1B1 ProteinP05026 (Uniprot-TrEMBL)
ATP1B2 ProteinP14415 (Uniprot-TrEMBL)
ATP1B3 ProteinP54709 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
BSG ProteinP35613 (Uniprot-TrEMBL)
BSGProteinP35613 (Uniprot-TrEMBL)
Basigin CD98hc complexComplexREACT_17413 (Reactome)
Basigin MMP1ComplexREACT_17528 (Reactome)
Basigin Mannose-carrying cell recognition moleculesComplexREACT_18084 (Reactome)
Basigin bound to CD43ComplexREACT_18170 (Reactome)
Basigin bound to CyPAComplexREACT_12714 (Reactome)
Basigin bound to MCTsComplexREACT_15052 (Reactome)
Basigin bound to integrinsComplexREACT_14081 (Reactome)
Basigin homodimerComplexREACT_13277 (Reactome)
Basigin-binding integrinsComplexREACT_14484 (Reactome)
CAV1 ProteinQ03135 (Uniprot-TrEMBL)
CAV1ProteinQ03135 (Uniprot-TrEMBL)
CD177 ProteinQ8N6Q3 (Uniprot-TrEMBL)
CD177ProteinQ8N6Q3 (Uniprot-TrEMBL)
CD2 ProteinP06729 (Uniprot-TrEMBL)
CD244 ProteinQ9BZW8 (Uniprot-TrEMBL)
CD244ProteinQ9BZW8 (Uniprot-TrEMBL)
CD2ProteinP06729 (Uniprot-TrEMBL)
CD47 ProteinQ08722 (Uniprot-TrEMBL)
CD47 bound to its ligandComplexREACT_12217 (Reactome)
CD47-binding SIRPsProteinREACT_12311 (Reactome)
CD47ProteinQ08722 (Uniprot-TrEMBL)
CD48 ProteinP09326 (Uniprot-TrEMBL)
CD48 bound to CD244ComplexREACT_12345 (Reactome)
CD48ProteinP09326 (Uniprot-TrEMBL)
CD58 bound to CD2ComplexREACT_12230 (Reactome)
CD58ProteinP19256 (Uniprot-TrEMBL)
CD84 ProteinQ9UIB8 (Uniprot-TrEMBL)
CD84 dimerComplexREACT_12135 (Reactome)
CD84ProteinQ9UIB8 (Uniprot-TrEMBL)
CD98hc complexComplexREACT_18154 (Reactome)
CEACAM heterodimerComplexREACT_12134 (Reactome)
CEACAM1 ProteinP13688 (Uniprot-TrEMBL)
CEACAM6 ProteinP40199 (Uniprot-TrEMBL)
CEACAM8 ProteinP31997 (Uniprot-TrEMBL)
CHEST MetaboliteCHEBI:17002 (ChEBI)
CHOL MetaboliteCHEBI:16113 (ChEBI)
CXADR ProteinP78310 (Uniprot-TrEMBL)
CXADR bound to JAMLComplexREACT_11619 (Reactome)
CXADRProteinP78310 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Caveolin-1 bound to BasiginComplexREACT_13130 (Reactome)
Collagen type I fibrilREACT_150867 (Reactome)
Complex of Tie2 Ang-1ComplexREACT_12688 (Reactome)
Complex of Tie2 Ang2ComplexREACT_12895 (Reactome)
CyP60 complexed with BasiginComplexREACT_12835 (Reactome)
DOK2 ProteinO60496 (Uniprot-TrEMBL)
DOK2ProteinO60496 (Uniprot-TrEMBL)
ESAM ProteinQ96AP7 (Uniprot-TrEMBL)
F11R ProteinQ9Y624 (Uniprot-TrEMBL)
F11RProteinQ9Y624 (Uniprot-TrEMBL)
FCER1G ProteinP30273 (Uniprot-TrEMBL)
FN1 dimerComplexREACT_14040 (Reactome)
FN1ProteinP02751 (Uniprot-TrEMBL)
FYNProteinP06241 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GP6 ProteinQ9HCN6 (Uniprot-TrEMBL)
GPVI

FceRI gamma FYN LYN

Collagen type I		ComplexREACT_20373 (Reactome)
GPVI

FceRI gamma FYN

LYN		ComplexREACT_20322 (Reactome)
GRB14 ProteinQ14449 (Uniprot-TrEMBL)
GRB14ProteinQ14449 (Uniprot-TrEMBL)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GRB2-1ProteinP62993-1 (Uniprot-TrEMBL)
GRB7 ProteinQ14451 (Uniprot-TrEMBL)
GRB7ProteinQ14451 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
Grb2 bound to Tie2ComplexREACT_12659 (Reactome)
HRASProteinP01112 (Uniprot-TrEMBL)
Heparan SulphateCHEBI:28815 (ChEBI)
INPP5D ProteinQ92835 (Uniprot-TrEMBL)
INPP5DProteinQ92835 (Uniprot-TrEMBL)
ITGA3ProteinP26006 (Uniprot-TrEMBL)
ITGA4ProteinP13612 (Uniprot-TrEMBL)
ITGA5ProteinP08648 (Uniprot-TrEMBL)
ITGA6ProteinP23229 (Uniprot-TrEMBL)
ITGAL ProteinP20701 (Uniprot-TrEMBL)
ITGAM ProteinP11215 (Uniprot-TrEMBL)
ITGAVProteinP06756 (Uniprot-TrEMBL)
ITGAX ProteinP20702 (Uniprot-TrEMBL)
ITGB1 ProteinP05556 (Uniprot-TrEMBL)
ITGB2 ProteinP05107 (Uniprot-TrEMBL)
ITGB3 ProteinP05106 (Uniprot-TrEMBL)
Integrin alpha5beta1 FibronectinComplexREACT_12353 (Reactome)
Integrin alpha5beta1ComplexREACT_12335 (Reactome)
Integrin alphaLbeta2 ComplexREACT_11837 (Reactome)
Integrin alphaMbeta2 JAM3ComplexREACT_12228 (Reactome)
Integrin alphaMbeta2ComplexREACT_12291 (Reactome)
Integrin alphaVbeta3 PECAM-1ComplexREACT_13361 (Reactome)
Integrin alphaVbeta3ComplexREACT_13287 (Reactome)
Integrin alphaXbeta2 AMICA1ComplexREACT_12224 (Reactome)
Integrin alphaXbeta2ComplexREACT_12091 (Reactome)
JAM-A HomodimerComplexREACT_12319 (Reactome)
JAM-B bound to JAM-CComplexREACT_12255 (Reactome)
JAM-B homodimerComplexREACT_12209 (Reactome)
JAM-C homodimerComplexREACT_12100 (Reactome)
JAM2 ProteinP57087 (Uniprot-TrEMBL)
JAM2ProteinP57087 (Uniprot-TrEMBL)
JAM3 ProteinQ9BX67 (Uniprot-TrEMBL)
JAM3ProteinQ9BX67 (Uniprot-TrEMBL)
KRASProteinP01116 (Uniprot-TrEMBL)
L1CAM ProteinP32004 (Uniprot-TrEMBL)
LDLComplexREACT_7774 (Reactome) LDL (low density lipoproteins) are complexes of a single molecule of apoprotein B-100 (apoB-100) non-covalently associated with triacylglycerol, free cholesterol, cholesterol esters, and phospholipids. LDL complexes contain single molecules of apoB-100, but their content of lipids is variable (Chapman et al. 1988; Mateu et al. 1972; Tardieu et al. 1976). High levels of LDL in the blood are strongly correlated with increased risk of atherosclerosis, and recent studies have raised the possibility that this risk is further increased in individuals whose blood LDL population is enriched in high-density (low lipid content) LDL complexes (Rizzo and Berneis 2006). The LDL complex annotated here contains an average lipid composition.
LFA-1 JAM-AComplexREACT_12182 (Reactome)
LYNProteinP07948 (Uniprot-TrEMBL)
Ligand to TREM-1 on the platelet membraneREACT_12176 (Reactome)
MAG ProteinP20916 (Uniprot-TrEMBL)
MERTK ProteinQ12866 (Uniprot-TrEMBL)
MERTK bound to its ligandComplexREACT_12164 (Reactome)
MERTK ligandsProteinREACT_12235 (Reactome)
MERTKProteinQ12866 (Uniprot-TrEMBL)
MMP1ProteinP03956 (Uniprot-TrEMBL)
Mannose-carrying cell recognition moleculesComplexREACT_18192 (Reactome)
Mn2+ MetaboliteCHEBI:18291 (ChEBI)
Mn2+MetaboliteCHEBI:18291 (ChEBI)
Monocarboxylate Transporter Set ProteinREACT_17955 (Reactome)
NRAS ProteinP01111 (Uniprot-TrEMBL)
Neutrophil CEACAMs affecting integrin binding to fibronectinProteinREACT_12292 (Reactome)
OLR1 ProteinP78380 (Uniprot-TrEMBL)
OLR1 bound to oxidized LDLComplexREACT_12181 (Reactome)
OLR1ProteinP78380 (Uniprot-TrEMBL)
P-selectin bound to its ligandComplexREACT_12193 (Reactome)
PECAM-1 PECAM-1ComplexREACT_13059 (Reactome)
PECAM-1 PLC gamma1 complexComplexREACT_13045 (Reactome)
PECAM-1 SHIP1 complexComplexREACT_13027 (Reactome)
PECAM-1 SHP-1 complexComplexREACT_13228 (Reactome)
PECAM-1 SHP-2 complexComplexREACT_13041 (Reactome)
PECAM-1 bound to CD177ComplexREACT_12173 (Reactome)
PECAM1ProteinP16284 (Uniprot-TrEMBL)
PI3KComplexREACT_4240 (Reactome)
PIK3CA ProteinP42336 (Uniprot-TrEMBL)
PIK3CB ProteinP42338 (Uniprot-TrEMBL)
PIK3R1 ProteinP27986 (Uniprot-TrEMBL)
PIK3R2 ProteinO00459 (Uniprot-TrEMBL)
PL MetaboliteCHEBI:16247 (ChEBI)
PLCG1ProteinP19174 (Uniprot-TrEMBL)
PPIA ProteinP62937 (Uniprot-TrEMBL)
PPIAProteinP62937 (Uniprot-TrEMBL)
PPIL2 ProteinQ13356 (Uniprot-TrEMBL)
PPIL2ProteinQ13356 (Uniprot-TrEMBL)
PROCProteinP04070 (Uniprot-TrEMBL)
PTPN11 ProteinQ06124 (Uniprot-TrEMBL)
PTPN11ProteinQ06124 (Uniprot-TrEMBL)
PTPN6 ProteinP29350 (Uniprot-TrEMBL)
PTPN6ProteinP29350 (Uniprot-TrEMBL)
Phosphorylated Tie2 in Tie2/Akt dimerComplexREACT_13046 (Reactome)
Platelet Factor 4REACT_12205 (Reactome)
SELE ProteinP16581 (Uniprot-TrEMBL)
SELL ProteinP14151 (Uniprot-TrEMBL)
SELP ProteinP16109 (Uniprot-TrEMBL)
SELPLG ProteinQ14242 (Uniprot-TrEMBL)
SELPLGProteinQ14242 (Uniprot-TrEMBL)
SHC1 ProteinP29353 (Uniprot-TrEMBL)
SHC1ProteinP29353 (Uniprot-TrEMBL)
SIRPA ProteinP78324 (Uniprot-TrEMBL)
SIRPG ProteinQ9P1W8 (Uniprot-TrEMBL)
SLC16A1 ProteinP53985 (Uniprot-TrEMBL)
SLC16A3ProteinO15427 (Uniprot-TrEMBL)
SLC16A8 ProteinO95907 (Uniprot-TrEMBL)
SLC3A2 ProteinP08195 (Uniprot-TrEMBL)
SLC7A10 ProteinQ9NS82 (Uniprot-TrEMBL)
SLC7A11 ProteinQ9UPY5 (Uniprot-TrEMBL)
SLC7A5 ProteinQ01650 (Uniprot-TrEMBL)
SLC7A6 ProteinQ92536 (Uniprot-TrEMBL)
SLC7A7 ProteinQ9UM01 (Uniprot-TrEMBL)
SLC7A8 ProteinQ9UHI5 (Uniprot-TrEMBL)
SLC7A9 ProteinP82251 (Uniprot-TrEMBL)
SOS-1 bound to Tie2 Grb2ComplexREACT_13320 (Reactome)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
SOS1ProteinQ07889 (Uniprot-TrEMBL)
SPN ProteinP16150 (Uniprot-TrEMBL)
SPNProteinP16150 (Uniprot-TrEMBL)
SelectinProteinREACT_12297 (Reactome)
Src family tyrosine kinases REACT_13328 (Reactome)
TAGs MetaboliteCHEBI:17855 (ChEBI)
TEK ProteinQ02763 (Uniprot-TrEMBL)
TEKProteinQ02763 (Uniprot-TrEMBL)
THBDProteinP07204 (Uniprot-TrEMBL)
TREM-1 bound to its ligandComplexREACT_12367 (Reactome)
TREM1 ProteinQ9NP99 (Uniprot-TrEMBL)
TREM1ProteinQ9NP99 (Uniprot-TrEMBL)
Tie2 Grb7 complexComplexREACT_18058 (Reactome)
Tie2 and Ang4 complexComplexREACT_12703 (Reactome)
Tie2 and Dok-2 complexComplexREACT_13019 (Reactome)
Tie2 and Grb14 complexComplexREACT_18185 (Reactome)
Tie2/Ang1 dimerComplexREACT_13336 (Reactome)
VLA-4 JAM-BComplexREACT_12179 (Reactome)
VLA-4ComplexREACT_11798 (Reactome)
activated protein CComplexREACT_2599 (Reactome)
activated thrombin thrombomodulinComplexREACT_5904 (Reactome)
p-5Y,S1119-TEK ProteinQ02763 (Uniprot-TrEMBL)
p-PECAM1 p-PECAM1ComplexREACT_12801 (Reactome)
p-Y663,Y686-PECAM1ProteinP16284 (Uniprot-TrEMBL)
p21 RAS GDPComplexREACT_2657 (Reactome)
p21 RAS GTPComplexREACT_4782 (Reactome)
p85 bound to Tie2ComplexREACT_13298 (Reactome)
pTie2 Ang-1ComplexREACT_13342 (Reactome)
pTie2 SHC1 complexComplexREACT_12988 (Reactome)
pTie2 and SHP2 complexComplexREACT_17975 (Reactome)
protein CComplexREACT_4912 (Reactome)
thrombin heavy chain ProteinP00734 (Uniprot-TrEMBL)
thrombin light chain ProteinP00734 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_12408 (Reactome)
ADPArrowREACT_12496 (Reactome)
AMICA1REACT_11154 (Reactome)
AMICA1REACT_12064 (Reactome)
ANGPT1REACT_12523 (Reactome)
ANGPT2REACT_12547 (Reactome)
ANGPT4REACT_12598 (Reactome)
ATPREACT_12408 (Reactome)
ATPREACT_12496 (Reactome)
BSGREACT_12497 (Reactome)
BSGREACT_12550 (Reactome)
BSGREACT_12637 (Reactome)
BSGREACT_13430 (Reactome)
BSGREACT_16882 (Reactome)
BSGREACT_16931 (Reactome)
BSGREACT_16941 (Reactome)
BSGREACT_16975 (Reactome)
BSGREACT_16988 (Reactome)
Basigin-binding integrinsREACT_13430 (Reactome)
CAV1REACT_12637 (Reactome)
CD177REACT_12006 (Reactome)
CD244REACT_12018 (Reactome)
CD2REACT_12031 (Reactome)
CD47-binding SIRPsREACT_12068 (Reactome)
CD47REACT_12068 (Reactome)
CD48REACT_12018 (Reactome)
CD58REACT_12031 (Reactome)
CD98hc complexREACT_16988 (Reactome)
CXADRREACT_11154 (Reactome)
Collagen type I fibrilREACT_1088 (Reactome)
Complex of Tie2 Ang-1mim-catalysisREACT_12496 (Reactome)
DOK2REACT_12575 (Reactome)
F11RREACT_12042 (Reactome)
FN1 dimerREACT_12043 (Reactome)
GDPArrowREACT_12516 (Reactome)
GPVI

FceRI gamma FYN

LYN		REACT_1088 (Reactome)
GRB14REACT_16885 (Reactome)
GRB2-1REACT_12511 (Reactome)
GRB7REACT_16914 (Reactome)
GTPREACT_12516 (Reactome)
Grb2 bound to Tie2REACT_12504 (Reactome)
Heparan SulphateArrowREACT_12497 (Reactome)
INPP5DREACT_12476 (Reactome)
Integrin alpha5beta1REACT_12043 (Reactome)
Integrin alphaLbeta2 REACT_12042 (Reactome)
Integrin alphaMbeta2REACT_12035 (Reactome)
Integrin alphaVbeta3REACT_12468 (Reactome)
Integrin alphaXbeta2REACT_12064 (Reactome)
JAM2REACT_12040 (Reactome)
JAM2REACT_12053 (Reactome)
JAM3REACT_12035 (Reactome)
JAM3REACT_12053 (Reactome)
LDLREACT_12039 (Reactome)
Ligand to TREM-1 on the platelet membraneREACT_12047 (Reactome)
MERTK ligandsREACT_12060 (Reactome)
MERTKREACT_12060 (Reactome)
MMP1REACT_16941 (Reactome)
Mannose-carrying cell recognition moleculesREACT_16975 (Reactome)
Mn2+REACT_12043 (Reactome)
Monocarboxylate Transporter Set REACT_16882 (Reactome)
OLR1REACT_12039 (Reactome)
PECAM-1 PECAM-1REACT_12408 (Reactome)
PECAM1REACT_12006 (Reactome)
PECAM1REACT_12468 (Reactome)
PI3KREACT_12475 (Reactome)
PLCG1REACT_12540 (Reactome)
PPIAREACT_12497 (Reactome)
PPIL2REACT_12550 (Reactome)
PROCArrowREACT_374 (Reactome)
PTPN11REACT_12509 (Reactome)
PTPN11REACT_16906 (Reactome)
PTPN6REACT_12552 (Reactome)
Phosphorylated Tie2 in Tie2/Akt dimerArrowREACT_12496 (Reactome)
Platelet Factor 4ArrowREACT_374 (Reactome)
REACT_1088 (Reactome) GPVI receptor has little affinity for soluble forms of collagen but binds collagen fibrils. Recent structural models indicate that each GPVI receptor complex could bind up to 3 collagen fibrils (Jung & Moroi 2008). The Src family kinases Fyn and Lyn constitutively associate with the GPVI-FceRIgamma complex in platelets and initiate platelet activation through phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) in the FceRIgamma chain, leading to binding and activation of the tyrosine kinase Syk. Downstream of Syk, a series of adapter molecules and effectors lead to platelet activation.
REACT_11154 (Reactome) JAM members, such as JAML, bind coxsackie and adenovirus receptor (CXADR) on epithelial and endothelial cells.
REACT_11994 (Reactome) Apart from its well-established interaction with VLA-4, JAM-B is also known to homodimerize.
REACT_11999 (Reactome) JAM-A is the most widely expressed member of the family, and has been shown to be expressed on endothelial and epithelial cells, on platelets, and on a number of leukocyte subsets. In endothelial cells, JAM-A locates to the tight junctions, where it appears to engage in homophilic binding to JAM-A on adjacent cells, an interaction that is considered to play a critical role in angiogenesis.
REACT_12006 (Reactome) CD177 is a 58- to 64-kDa glycosylphosphatidylinositol-anchored glycoprotein expressed exclusively by neutrophils, neutrophilic metamyelocytes, and myelocytes, but not by any other blood cells. It has been shown that neutrophil-specific CD177 is a heterophilic binding partner of PECAM-1, constituting a novel pathway that promotes neutrophil transmigration.
REACT_12018 (Reactome) CD2, CD48, CD84, CD244 and CD58 have a similar extracellular domain arichitecture consisting of two IgSF domains. CD244 is closely related to CD84 in having a long cytoplasmic tail with tyrosine-based motifs (TxYxxI/V) resembling immunoreceptor tyrosine-based inhibitory motifs (ITIMs). CD2 has a cytoplasmic domain with proline-rich regions which recruit an Src homology 3 (SH3)- containing protein called CD2-associated protein (CD2AP). CD48 is glycosyl-phosphatidyl-inositol (GPI)-anchored to the membrane.

CD244 is known to be activated by binding to CD48 in humans.

REACT_12027 (Reactome) CD84 is a homophilic receptor expressed on T cells, B cells, dendritic cells, monocytes, macrophages, eosinophils, mast cells, granulocytes, and platelets. CD84 expression increases following activation of T cells, B cells, and dendritic cells. CD84 homophilic engagement is known to induce platelet stimulation.
REACT_12029 (Reactome) JAM-C has been detected in epithelial-cell desmosomes. JAM-C homodimers are prominently located in endothelial-cell tight junctions.
REACT_12031 (Reactome) The crystal structure of the human CD2-CD58 complex also shows that most of the residues at the interface between these two proteins are charged and form several inter-protein salt bridges.
REACT_12035 (Reactome) Recruitment of monocytic cells to the vessel wall by platelets is mediated via CD11b/CD18 (Mac-1) and platelet JAM-C. In the case of dendritic cells, this interaction leads to their activation and platelet phagocytosis. This process may be of importance for progression of atherosclerotic lesions.
REACT_12039 (Reactome) The lectin-like oxidized low density lipoprotein receptor- 1 (Lox-1) mediates the recognition and internalization of oxidatively modified low density lipoprotein. This interaction results in a number of pro-atherogenic cellular responses that probably play a significant role in the pathology of atherosclerosis.
REACT_12040 (Reactome) Several key IgSF cell adhesion molecules engage integrin and in so doing impact on the multi-step paradigm of leukocyte emigration. The interaction between JAM-B and VLA-4 is facilitated by prior engagement of JAM-B with JAM-C.
REACT_12042 (Reactome) JAM-A plays a key role in leukocyte transmigration and inflammatory extravasation. Transmigration of human leukocytes has been shown to involve heterophilic interactions of JAM-A with its integrin receptor LFA-1.
REACT_12043 (Reactome) Alpha5beta1 integrin was the first integrin shown to bind fibronectin (FN1). Unlike other FN1-binding integrins it is a specialist at this task. In solution FN1 occurs as a dimer. Binding to alpha5beta1 integrin stimulates FN1 self-association; blocking the RGD-cell binding domain of FN1 blocks fibril formation (Fogerty et al. 1990). FN1 binding is believed to induce integrin clustering, which promotes FN1-FN1 interactions. Integrin clustering is mediated by association between integrins and intracellular actin stress fibers (Calderwood et al. 2000). Binding of integrins to each of the monomers in the FN1 dimer pair is thought to trigger a conformational change in FN1 that exposes 'cryptic' FN1 binding sites that allow additional fibronectin dimers to bind without the requirement for pre-association with integrins (Singh et al. 2010). This non-covalent interaction may involve interactions with fibrillin (Ohashi & Erickson 2009). I1-5 functions as a unit that is the primary FN matrix assembly domain (Sottile et al. 1991) but other units are likely to be involved (Singh et al. 2010). Other integrins able to bind FN1 include alphaIIbBeta3, which is highly expressed on platelets where it predominantly binds fibrinogen leading to thrombus formation but also binds FN1 (Savage et al. 1996). Alpha4beta1 mediates cell-cell contacts and cell-matrix contacts through the ligands VCAM-1 and FN1, respectively (Humphries et al. 1995). Integrins alpha3beta1, alpha4beta7 and alphaVbeta1, 3 and 6 are all reported to bind FN1 (Johansson et al. 1997)


Tenacious binding of free fibronectin to cells leads to enhanced fibronectin matrix assembly and the formation of a polymerized fibronectin "cocoon" around the cells. This process is enhanced in the presence of CEACAM molecules.
REACT_12047 (Reactome) The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Although the identity and occurrence of the natural TREM-1 ligands are so far unknown, the presence of a ligand for TREM-1 on human platelets has been established. It has been suggested that TREM1 recognizes soluble proteins or cell-surface proteins which are upregulated as a result of inflammation and/or tissue damage and also bacterial LPS (Tessarz & Cerwenka 2008).
REACT_12053 (Reactome) JAM-B and -C bind each other and are strongly expressed by endothelial cells of high endothelial venules, the predominant site of leukocyte extravasation. JAM-B and -C also bind to the leukocyte integrins VLA-4 and Mac-1 respectively.
REACT_12060 (Reactome) MerTK appears to be required for ingestion of apoptotic cells by professional phagocytes such as monocytes/macrophages, retinal pigment epithelial cells and dendritic cells. Mer appears to be able to induce the cytoskeletal remodelling that is required for engulfment during phagocytosis. For instance, a deletion in the MERTK gene was identified as the underlying cause for retinal dystrophy which involves an impairment in the ingestion of shed photoreceptor cell fragments by retinal pigment epithelial cells.

The biological ligands for MerTK are two highly similar vitamin K-dependent proteins, Gas6 and protein S (PS), a negative regulator of blood coagulation. Both proteins are composed an N-terminal region containing multiple post-translationally modified gamma-carboxyglutamic acid residues (Gla). The Gla region possesses the ability to interact in a conformationally specific manner with negatively charged membrane phospholipids, which is thought to mediate the binding of both Gas6 and PS to apoptotic cells. In this way, they are thought to act as recognition bridges between apoptotic cells and the phagocyte cell that ingest them.

REACT_12064 (Reactome) Although JAM-C is better known for its interaction with MAC-1, an interaction with CD11c/CD18 (known as alpha X beta 2), has also been described.
REACT_12068 (Reactome) Integrin-associated protein (IAP or CD47) is a receptor for thrombospondin family members, a ligand for the transmembrane signaling protein SIRP-alpha and -gamma, and a component of a supramolecular complex containing specific integrins, heterotrimeric G proteins and cholesterol.
REACT_12073 (Reactome) The presence of CEACAM dimers was shown to lead to an increase in the binding of the integrin alph5 beta1 receptor to its ligand fibronectin, without changing its cell surface levels, resulting in increased adhesion of these cells to fibronectin.
REACT_12081 (Reactome) PSGL-1 is expressed as a homodimer of two 120-kDa subunits that binds all four selectins, with the highest affinity for P-selectin, and is known to be constitutively expressed on the surface of platelets and most types of leukocytes. Besides playing a critical role in the inflammatory response by mediating leukocyte-leukocyte and leukocyte-endothelium interactions, PSGL-1 also participates in the hemostatic process by mediating leukocyte-platelet interactions.
REACT_12408 (Reactome) PECAM-1 is capable of transmitting information into the cell following its engagement and becomes tyrosine-phosphorylated during the platelet aggregation process. The Src family of tyrosine kinases (more specifically, Src, Lyn, and c-src) has been widely implicated in the phosphorylation of PECAM-1. Conserved tyrosine residues (Tyr663 and Tyr686) within the PECAM-1 cytoplasmic ITIM motif have been shown to become phosphorylated. Tyrosine phosphorylation of PECAM-1 prompts its association with intracellular signal transduction molecules.
REACT_12409 (Reactome) ShcA, an SH2-containing adapter protein, acts as a scaffold for the assembly of signaling proteins involved in the activation of the Ras-MAPK pathway, and potentially other signaling pathways.
ShcA is one of the binding partners of endogenous Tie2 receptor on vascular endothelial cells. After Tie2 stimulation by Ang-1 interaction, ShcA associates with Tie2 and becomes tyrosine-phosphorylated. ShcA interacts with the cytoplasmic domain of Tie2 and Y1102 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA. ShcA leads to a reduction of tyrosine phosphorylation of p85 subunit of PI3-kinase and is involved in the inhibition of endothelial cell migration and survival.
REACT_12419 (Reactome) PECAM-mediated adhesion is complex, because it is capable of binding both to itself (homophilic adhesion) and to non-PECAM ligands (heterophilic adhesion). The trans-homophilic interaction between the two PECAM-1 molecules is mediated by their NH2-terminal membrane distal Ig homology domains 1 and 2 plus the proper spacing formed by the six Ig-homology domains.
REACT_12431 (Reactome) Receptor tyrosine kinase activation and signaling are typically initiated via dimerization of the receptors through homo-oligomeric ligand binding.

Angiopoietin1 may form homotrimers, but in most cases it assembles into higher-order multimers. This oligomerization is mediated by the N-ter coiled coil domain (CCD).
The binding of Ang1 oligomers to Tie2 promotes the dimerization of Tie2, which is further assisted by the interaction between the kinase domains of the receptors.
REACT_12468 (Reactome) Alpha v beta 3 integrin is one of the potential heterophilic ligands of PECAM-1 that is involved in down-regulation of T-cell responses. The heterophilic interaction of alpha v beta 3 integrin on endothelial cells with PEACAM-1 on leukocytes increases the adhesive function of beta integrins on T cells, monocytes, neutrophils and NK cells suggesting that leukocyte PEACAM-1 act as a signaling molecule.
REACT_12475 (Reactome) The p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase) associates with Tie2, most likely at phosphotyrosine 1102. This association leads on to the activation of Akt/PKB, a process linked to cell survival and antiapoptosis, and that may in part account for Tie2's role in vascular growth and maintenance.
REACT_12476 (Reactome) PECAM/CD31 is a member of the immunoglobulin superfamily (IgSF) and has been implicated to mediate the adhesion and trans-endothelial migration of T-lymphocytes into the vascular wall, T cell activation and angiogenesis. It has six Ig homology domains within its extracellularly and an ITIM motif within its cytoplasmic region.
PECAM-mediated adhesion is complex, because it is capable of binding both to itself (homophilic adhesion) and to non-PECAM ligands (heterophilic adhesion). The trans-homophilic interaction between the two PECAM-1 molecules is mediated by their NH2-terminal membrane distal Ig homology domains 1 and 2 plus the proper spacing formed by the six Ig-homology domains.
REACT_12496 (Reactome) The dimerization of Tie2 leads to autophosphorylation and activation of its kinase domain. There are multiple tyrosine phosphorylation sites in the Tie2 kinase domain. The phosphorylated tyrosine residues provide the interaction site for the SH2 domains of other downstream signaling molecules like PI3K, Grb2, SHP2 etc.
REACT_12497 (Reactome) Cyclophilin A (CyPA)1 is an intracellular protein belonging to the immunophilin family and is recognized as the major target for the potent immunosuppressive drug cyclosporin A. CD147 is the natural cell surface receptor for CyPA. It is demonstrated that CD147 is an essential component in the CyPA-initiated signaling cascade that culminates in ERK activation.
REACT_12504 (Reactome) Grb2 binds directly to autophosphorylated Tie2 receptor. GRB2 also contains two SH3 domains, which bring various ligands to the sites of active signaling. One of the SH3 domains on Tie2-bound Grb2 recruits SOS1, an activating nucleotide exchange factor for Ras. This interaction of Sos1 to Grb2 brings Sos1 towards Ras molecules leading to Ras activation. Ras is implicated in the MAP kinase cascade, a pathway in cell growth stimulation, migration and differentiation.
REACT_12509 (Reactome) PECAM-1 becomes tyrosine-phosphorylated during the platelet aggregation process; the phosphorylation of two tandem tyrosine residues (Y663 and Y686) within the cytoplasmic domain is required for downstream signalling events. Phosphorylation creates docking sites for the protein-tyrosine phosphatase SHP-2. The interaction between SHP-2 and PECAM-1 is dependent upon integrin-mediated platelet/platelet interactions and occurs via the Src homology 2 (SH2) domains of the phosphatase and highly conserved phosphatase-binding motifs encompassing phosphotyrosines 663 and 686 within the cytoplasmic domain of PECAM-1.
REACT_12511 (Reactome) Tie2/Tek provide mitogenic signals to endothelial cells by promoting the association of Grb2 to one of their phosphotyrosines. Grb2 is an adaptor protein that has been linked to activation of Ras and mitogen activated protein kinase (MAPK) cell growth signaling pathways. Grb2 also binds to the Y1102 of the kinase domain of Tie2 with one of its SH2 doamins.
REACT_12516 (Reactome) Sos-1 bound to Grb2:Tie2 complex promotes the exchange of inactive Ras-GDP to active Ras-GTP.
REACT_12523 (Reactome) Tie receptors and their angiopoietin ligands play a critical role in angiogenesis or blood vessel formation. They are considered to control numerous signaling pathways that are involved in diverse cellular processes, such as cell migration, proliferation, survival and reorganization of the actin cytoskeleton.

Tie (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains) represents a class of receptor tyrosine kinases (RTKs) that are predominately expressed by vascular endothelial cells. The angiopoietins are a family of growth factors that are largely specific for endothelium and they bind to Tie2/Tek RTKs.

Tie2 signaling initially involves the activation of Tie2 by the interaction of angiopoietin 1. Angiopoietin interacts with the Tie2 receptor with its fibrinogen like domain (FLD). This interaction leads to the dimerization of both the receptor and the ligand, and later initiate the trans-phosphorylation of Tie2.
REACT_12540 (Reactome) Like SHP-1 and SHP-2, PLC-gamma 1 also interacts with PECAM-1. PLC-gamma 1 binds with both the tyrosine residues (Y663 and Y686). Unlike the N-SH2 domain, the C-SH2 domain on PLC-gamma 1 can only bind phosphotyrosine 663. The engagement of PECAM-1 with PLC-gamma 1 may lead to PLC-gamma 1 activation and subsequent calcium influx.
REACT_12547 (Reactome) The major ligands for Tie2 are Ang1 and Ang2. Ang1 has been considered as the primary activating ligand of Tie2 whereas role of Ang2 remains controversial. Ang2 acts as stimulating in some studies and inhibiting in others. The activity of Ang2 is concentration dependent. Ang2 possesses similar receptor affinity to Ang1 and they both share the same binding site on Tie2. The Ang2 fibrinogen domain is solely responsible for receptor recognition and binding, the coiled-coil motif mediates its oligomerization.
REACT_12550 (Reactome) Basigin serves as a signaling receptor for extracellular cyclophilins. Its been reported that cyclophilin 60 (Cyp60), a distinct member of the cyclophilin family is involved in the regulation of intracellular transport of basigin. The mechanism of this activity involves interaction of Cyp60 with the proline-containing region within or adjacent to the predicted transmembrane domain basigin. Cyp60 is co-localized with basigin at the plasma membrane suggesting that Cyp60 may function as a chaperone escorting basigin through the secretory pathway.
REACT_12552 (Reactome) The phosphorylation of two tandem tyrosine residues (Y663 and Y686) within the cytoplasmic domain of PECAM-1 is required for the downstream signalling events observed following PECAM-1 ligation. Both SH2 domains of SHP-1 are required in tandem to bind PECAM-1.
REACT_12575 (Reactome) Dok-2 is a member of a docking proteins class, termed the DOK family. The DOK family members are characterized by an N-terminal pleckstrin homology (PH) domain followed by a central PTB domain and a proline- and tyrosine-rich C-terminal tail. Dok-2 is recruited to activated Tie2 via its PTB domain, which results in its subsequent tyrosine phosphorylation, thereby establishing binding sites for the small GTPase-activating protein for Ras, p120RasGAP (RasGAP) and the adapter protein Nck. The binding of DOK to the receptor leads to Nck recruitment and subsequent phosphorylation. Binding of Pak to Nck follows. this brings about the Ang-1-dependent phosphorylation of Pak in endothelial cells.
REACT_12593 (Reactome) Basigin (Bsg) is a highly glycosylated transmembrane protein belonging to the Ig superfamily with two Ig domains. Bsg forms homo-oligomers on the plasma membrane in a cis-dependent manner. The N-terminal Ig-like domain is functionally important in oligomer formation.

REACT_12598 (Reactome) Ang4 represents a third protein of the Ang family that binds to the Tie2 receptor. The mouse Ang3 and human Ang4 are interspecies orthologs. Ang4 acts as an activating ligand and induces phosphorylation in Tie2.
REACT_12637 (Reactome) Stromal fibroblasts secrete multiple matrix metalloproteinases (MMP)1 that can promote tumor cell growth, survival, invasion, angiogenesis, and metastasis. Basigin on the surface of carcinoma cells, stimulates production of MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), and MMP-3 (stromelysin). Basigin has been shown to co-immunoprecipitate with caveolin-1. The second Ig domain of Basigin is required for this association, which leads to decreased Besigin self-association on the cell surface. Therefore, caveolin-1 is a negative regulator of CD147 self-association, and its MMP-inducing activity.
REACT_13430 (Reactome) Basigin is a widely distributed cell-surface protein with two immunoglobulin domains and has shown to associate with both the integrins alpha3beta1 and alpha6beta1.
REACT_16882 (Reactome) Proton-coupled monocarboxylate transporters (MCT) MCT1, MCT3, and MCT4 form heterodimeric complexes with the cell surface glycoprotein CD147 and exhibit tissue-specific polarized distributions that are essential for maintaining lactate and pH homeostasis.
REACT_16885 (Reactome) Grb14 is also one of the signaling partners of Tie2. The SH2 domain of Grb2 mediates binding to Tie2. It binds residues Y816, Y1108 and Y1113 respectively, in the C-terminal tail region of Tie2/Tek.
REACT_16906 (Reactome) Shp2 interact with Tyr816 in the juxtamembrane region and Tyr1108 and Tyr1113, respectively, in the C-terminal tail region of Tie2/Tek.
REACT_16914 (Reactome) Grb7 was initially identified as an EGF receptor binding protein and thereafter many binding partners have been reported. Grb7 interacts with Tie2/Tek in a phosphotyrosine-dependent manner through its SH2 domain.
REACT_16931 (Reactome) CD43, a major leukocyte cell surface sialoglycoprotein, interacts directly with Basigin.
REACT_16941 (Reactome) Basigin expressed on the surface of most tumor cells, stimulates stromal cells to produce elevated levels of several matrix metalloproteinases (MMP), including interstitial collagenase (MMP-1). MMPs have been implicated in several aspects of tumor progression, including invasion through basement membranes and interstitial matrices, angiogenesis, and tumor cell growth. Basigin not only stimulates the production of MMP-1 but also forms a complex with MMP-1 at the tumor cell surface and this interaction may be important in modifying the tumor cell pericellular matrix to promote invasion.
REACT_16975 (Reactome) Based on in vitro affinity chromatography study, basigin was found to bind to high mannose-carrying cell recognition molecules, such as myelin-associated glycoprotein, L1 and the beta2-subunit of Na+/K+-ATPase.
REACT_16988 (Reactome) CD97hc is a multifunctional glycoprotein with a single transmembrane domain, is highly expressed on proliferating cells, and functions as a chaperone for transporters. CD98hc forms disulfide-bonded heterodimers with at least seven different light chains (SLC7A5-11) that serve as amino acid transporters. Covalent cross-linking, mass spectrometric protein identification, and co-immunoprecipitation shows selective CD147 association with CD98hc complex.
REACT_374 (Reactome) Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
SELPLGREACT_12081 (Reactome)
SHC1REACT_12409 (Reactome)
SOS-1 bound to Tie2 Grb2mim-catalysisREACT_12516 (Reactome)
SOS1REACT_12504 (Reactome)
SPNREACT_16931 (Reactome)
SelectinREACT_12081 (Reactome)
Src family tyrosine kinases mim-catalysisREACT_12408 (Reactome)
TEKREACT_12523 (Reactome)
TEKREACT_12547 (Reactome)
TEKREACT_12598 (Reactome)
TREM1REACT_12047 (Reactome)
Tie2/Ang1 dimerREACT_12496 (Reactome)
VLA-4REACT_12040 (Reactome)
activated protein CArrowREACT_374 (Reactome)
activated thrombin thrombomodulinmim-catalysisREACT_374 (Reactome)
p-PECAM1 p-PECAM1ArrowREACT_12408 (Reactome)
p-Y663,Y686-PECAM1REACT_12476 (Reactome)
p-Y663,Y686-PECAM1REACT_12509 (Reactome)
p-Y663,Y686-PECAM1REACT_12540 (Reactome)
p-Y663,Y686-PECAM1REACT_12552 (Reactome)
p21 RAS GDPREACT_12516 (Reactome)
p21 RAS GTPArrowREACT_12516 (Reactome)
pTie2 Ang-1REACT_12409 (Reactome)
pTie2 Ang-1REACT_12475 (Reactome)
pTie2 Ang-1REACT_12511 (Reactome)
pTie2 Ang-1REACT_12575 (Reactome)
pTie2 Ang-1REACT_16885 (Reactome)
pTie2 Ang-1REACT_16906 (Reactome)
pTie2 Ang-1REACT_16914 (Reactome)

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1794"
Personal tools