Semaphorin interactions (Homo sapiens)

From WikiPathways

Revision as of 10:42, 10 June 2014 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
2, 7, 10, 11, 1619303234, 36, 39, 4729, 423, 44, 484628, 343839, 20, 40323, 8, 44, 4823, 311, 9, 2641, 485, 27414, 251822, 339, 15, 4521, 2412, 4317, 376, 41355, 13, 27RhoA/B/CGTP Phospho-activated smooth muscle/non-muscle myosin 2 SEMA6APLXNA2,PLXNA4 Sema3ANrp-1PlexinARac1-GTPPAK R-Ras-GTP Phosphorylated smooth muscle/non-muscle myosin 2 regulatory light chains RAC1-GTP FARP2PIP5KIgamma CRMP's tetramers Plexin-A1-4FYNFARP2 Active LIMK1 PAK Sema3ANrp-1PlexinAFynCdk5pCRMP's RAC1-GTP SEMA4DCD72 SEMA4D dimer SEMA4D dimer Sema3ANrp-1pPlexinAFynFesRac-1-GTPRnd1 NRP1p-Plexin-A1-4FYN cytosolRnd1-GTP Sema3A dimer SEMA4D dimer pPlexin-B1Met Sema3A dimer Sema3ANRP-1pPlexin-Afyn GSK3beta phosphorylated CRMP's 1-5 p-CRMP tetramers LARG and PDZ-RhoGEF DAP12TRIM2 pPlexin-B1Met p-Plexin-A1-4 SEMA4D dimer Sema3A dimer Sema4DpPlexin-B1MetRnd1 Rnd1-GTP pPlexin-B1Met SEMA7APLXNC1 RhoA/B/CGTP Sema3ANRP-1pPlexin-Afyn p-Plexin-A1-4 pCRMP's tertramers p-2Y-PAK PlexinA1-4FYNpCdk5p53 Rnd1-GTP Sema3ANRP-1pPlexin-AFynFes HSP-90 SEMA4DpPlexin-B1ErbB2 complex VAV1 Rho/Rac effectorsGTP pCdk5p35 SEMA4APLXND1 RAC1-GTP RhoA/B/C Plexin-B1ErbB2 RAC1-GTP PlexinA1-4FYNCDK5p-CRMPs pCofilin Active LIMK-1 Sema3A dimer PAK Sema3A dimer SEMA4DpPlexin-B1ErbB2 complex Plexin-A1-4 ROCK PlexinA1-4FYNCdk5p53p-CRMP tetramers Plexin-A1-4 Integrin alpha1beta1 RAC1-GTP Sema3ANP-1Plexin-AFesCRMP SEMA7AIntegrin alpha1beta1 R-Ras-GDP Sema3A dimer Smooth muscle/non-muscle myosin 2 heavy chains Sema3ANrp-1pPlexinAFynFesRac-1-GTP Sema3ANRP-1pPlexin-Afyn Activated ROCKRhoA/B/CGTP pPlexin-B1Met R-Ras-GTP PAK homodimer NRP1PlexinA1-4FYNCdk5p53p-CRMP tetramers PLXNA1TREM2DAP12 Sema4DpPlexin-B1MetRAC1-GTP SEMA6DPLXNA1TREM2DAP12 DAP12TRIM2 Sema4DpPlexin-B1ErbB2Rac1Rnd1 Sema4DpPlexin-B1Met Sema3ANRP-1pPlexin-AFynFes Plexin-A1-4 VAV1 Rho/Rac effectorsGTP Sema4DpPlexin-B1ErbB2Rac1Rnd1 Plexin-A1-4 FynpCdk5p53 Sema3A dimer Sema3ANrp-1PlexinAFynCdk5pCRMP's CRMP's 1-5 Sema3ANrp-1pPlexinAFynFesRac-1-GTP Nrp-1PlexinAFynCdk5pCRMP's p-Plexin-A1-4 Sema3ANrp-1PlexinAFynpCdk5 Sema4DPlexin-B1p190RhoGAPRacRnd1 Sema4DpPlexin-B1Met Sema3A dimer SEMA4D dimer pCRMP's tetramers pPlexin-B1ErbB2 Plexin-A1-4FYN SEMA4D dimer Cdk5 phosphorylated CRMP1-5 Plexin-A1-4FYN Sema3A dimer RhoA NRP1PlexinA1-4FYN Rnd1-GTP NRP1p-Plexin-A1-4FYN SEMA3APLXND1 SEMA4D dimer NRP1Plexin-A1-4FYN DAP12 dimer Sema3ANRP-1pPlexin-AFynFes NRP1PlexinA1-4FYNpCdk5p53 PLXNA2,PLXNA4 SEMA4DPTPRC Sema3ANrp-1PlexinAFyn Sema3A dimer Smooth muscle/non-muscle myosin II pPlexin-B1ErbB2 NRP1p-Plexin-A1-4FYN pPlexin-B1ErbB2 Sema4DpPlexin-B1Met SEMA4DpPlexin-B1ErbB2 complex Integrin alpha1beta1 Plexin-A1-4FYN Smooth muscle/non-muscle myosin 2 regulatory light chains Sema4DPlexin-B1Rac-Rnd1LARG/PDZ-RhoGEF p-Plexin-A1-4 PIP5K1gammaTalin-1 RhoA/B/C SEMA4D dimer RhoA NRP1PlexinA1-4FARP2FYN Sema3ANrp-1Plexin AFyn RAC1-GTP Plexin-A1-4 Sema3ANrp-1pPlexinAFynFesRac-1-GTP NRP1PlexinA1-4FYN cytosolSema3ANrp-1pPlexinAFynFesRac-1-GTP Fes phosphorylated CRMP's 1-5 Sema3A dimer FynpCdk5p53 cytosolSEMA5APLXNB3 pCdk5p35 NRP1p-Plexin-A1-4FYN p-Plexin-A1-4 pCdk5p35 Sema3ANRP-1pPlexin-Afyn Plexin-A1-4 NRP1p-Plexin-A1-4FYN Plexin-A1-4 R-Ras-GDP cytosolSmooth muscle/non-muscle myosin 2 heavy chains Plexin-A1-4FYN Plexin-A1-4 RAC1-GDP Sema3ANRP-1pPlexin-Afyn Sema3ANRP-1pPlexin-AFynFes Sema4DpPlexin-B1MetRnd1 Sema3ANRP-1pPlexin-AFynFes FynpCdk5p53 Sema3ANrp-1PlexinARac1-GTPpPAK Sema3ANRP-1pPlexin-AFynFes Rnd1-GTP Sema3A dimer Sema3A dimer Cdk5p35 p-Plexin-A1-4 PLXNA1TREM2DAP12 Plexin-B1Met RhoA,B,CGDP Sema4DpPlexin-B1Met cytosolpLIMK dimerHSP-90 RhoA/B/C Active LIMK1 NRP1p-Plexin-A1-4FYN DAP12 dimer SEMA4D dimer RAC1-GTP Sema3ANRP-1pPlexin-Afyn SEMA4APLXND1PLXNC1GDP SEMA6A GTP p-S522-DPYSL2 PLXND1 PLXNA4 FYNMYL6 SEMA4D GTP ROCK2 SEMA4D ADPp-Y-PLXNA1 PTPRC Sema3ANRP-1pPlexin-AFynFesPLXNA2p-Y-PLXNB1 SEMA4DpPlexin-B1ErbB2 complexMYH10 NRP1 PLXNA3 SEMA7A LIM Kinases, phosphorylatedp-S544-DPYSL4 ARHGEF11 ATPPLXNA3 RAC1 SEMA3A PLXND1 PLXNA2Sema3ANrp-1Plexin AFynPLXNA1 Activated ROCKRhoA/B/CGTPPLXNA1 GTPp-Y-PLXNA1 GTP SEMA3E RAC1 Sema3A dimerMET PLXNA3 p-Y-PLXNA1 GDP SEMA3Ep-Y-PLXNA4 PLXNA2ATPPLXNA4 CRMP's tetramersPLXND1LARG and PDZ-RhoGEFGTP Sema3ANrp-1pPlexinAFynFesRac-1-GTPRnd1RAC1-GTPp-Y-DPYSL5 NRP1 RND1 MET PLXNA1 p-Y-PLXNB1 TYROBP p-Y-PLXNA1 p-S,T508-LIMK1 HSP-90RAC1 DPYSL5 Sema3ANrp-1pPlexinAFynFesRac-1-GTPCDK5 PAKSEMA4A RND1 ADPPlexin-B1MetADPRHOA PLXNA2MYL6 ARHGAP35 Phospho-activated smooth muscle/non-muscle myosin 2RhoA,B,CGDPNRP1 p-T509,T514,S518,S522-CRMP1 ADPPlexin-B1ErbB2Sema4DPlexin-B1Rac-Rnd1LARG/PDZ-RhoGEFNRP1 ITGB1 PIP5K1gammaTalin-1GDPERBB2 CRMP1 SEMA4D RHOA GDP RHOC HSP90AA1 SEMA4DPTPRCRnd1-GTPADPp-T508-LIMK1 SEMA4D SEMA3A RAC1 p-Y-PLXNA2GDP p-T509,T514,S518,S522-DPYSL3 p-Y-PLXNA2RND1 Sema3ANrp-1PlexinAFynCdk5pCRMP'sRND1 Mg2+ p-Y-DPYSL4 SEMA4Ap-Y15-CDK5 SEMA7APLXNC1ROCKPLXNA2p-Y-PLXNA3 MET RAC1-GTPFARP2 SEMA4D R-Ras-GDPSema3ANP-1Plexin-AFesCRMPATPPLXNA4 NRP1PlexinA1-4FARP2FYNSEMA3A p-Y-PLXNA1 NRP1p-T19,S20-MYL12BPLXNA4 FARP2PLXNA3 p-Y-PLXNA3 MYL12Bp-Y-PLXNB1 RAC1 p-T508-LIMK1NRP1 SEMA7AADPGTP PLXNA3 ATPFES RHOC GTP PiRND1 SEMA5A ADPSema3ANrp-1PlexinAFynCdk5pCRMP'sGTP LIM KinasesSEMA3A PIP5K1C SEMA7A SEMA6DPLXNA1TREM2DAP12RAC1-GDPPLXNA4 PiRAC1 p-Y-PLXNA4 RRAS MET RRAS DPYSL3 GDP PLXND1R-Ras-GTPERBB2 PLXNA4 Sema3ANrp-1PlexinAFynADPDPYSL2 p-S522-DPYSL3 ATPRhoA/B/CGTPPLXNA1TREM2DAP12MYH10 TLN1 p-Y-PLXNA3 PLXNB1 ARHGAP35p-Y-PLXNA3 Sema3ANrp-1PlexinARac1-GTPpPAKRHOA PLXNA3 SEMA6D RND1 TREM2 RhoA FYNPTPRCGTP Sema3ANrp-1PlexinARac1-GTPPAKATPPLXNA4 GTP NRP1 NRP1 FYNFYNPLXNA1 PAK1 Mg2+ PLXNA3 SEMA3A ATPPAK homodimerGTP FARP2 Sema3A dimerp-S3-CFL1 SEMA3A NRP1 FESMYH9 HSP90AB1 TLN1p-S534-DPYSL5 p-Y-PLXNA2LIMK1FARP2PIP5KIgammaPLXNA1 p-Y-PLXNB1 p-Y-PLXNA3 CDK5R1TYROBP RRAS SEMA6AITGB1 FES ADPp-Y-PLXNB1 PLXNB1 Sema4DpPlexin-B1MetRAC1-GTPp-S522-CRMP1 p-S141,T402-PAK2p-Y-PLXNA3 p-S,T508-LIMK1 PLXNA4 GTPGTP NRP1 GTP CDK5R1pLIMK dimerHSP-90ERBB2 FYNSEMA4D PAK1 RRAS GDPSEMA6APLXNA2,PLXNA4GTP MET PLXNB3 ATPGTP GTP FYNSEMA4D ADPp-T509,T514,S518,S522-DPYSL2 NRP1PlexinA1-4FYNATPITGA1 p-S144,T423-PAK1 DPYSL4 R-Ras-GTPRHOB SEMA3A p-S544-DPYSL4 p-Y-CRMP1 SEMA4D dimerPLXNA1 p-S534-DPYSL5 FYNPAK2p-Y-PLXNA4 ADPCD72 PLXNA1 Cdk5p35SEMA4D p-Y-DPYSL2 p-Y-PLXNB1 CDK5R1NRP1 SEMA3A ATPPIP5K1C SEMA4D dimerMYL9 SEMA3A p-Y15-CDK5 MYH11 Sema4DpPlexin-B1MetRnd1SEMA3A p-Y-PLXNA2FES SEMA6DSEMA4DCD72PLXNA1 MYH9 GSK3BSema4DPlexin-B1p190RhoGAPRacRnd1SEMA5AATPPLXNA2GTP MYH11 FES SEMA4D CD72SEMA3A RAC1 SEMA3A SEMA4DPLXNA1 FYNPLXNA2RHOA SEMA5APLXNB3PLXNA1 FES Integrin alpha1beta1p-Y-PLXNA2RND1 pCofilin Active LIMK-1Plexin-A1-4FYNRHOB p-Y-PLXNB1 PLXNA2PLXNC1 GTP NRP1 p-T19,S20-MYL9 p-Y-PLXNA2Smooth muscle/non-muscle myosin IIp-Y-PLXNA1 PiPAK2SEMA4D PLXNA4 RhoA ARHGEF12 PLXNA3 ADPATPMYH14 TREM2 RAC1 R-Ras-GDPFYNFYNATPFYNSEMA3A p-Y-DPYSL3 ERBB2 CDK5R1p-Y-PLXNA4 p-Y-PLXNA4 ROCK1GTP NRP1 p-Y-PLXNA4 p-Y15-CDK5 Sema4DpPlexin-B1ErbB2Rac1Rnd1ADPPLXNA2FYNMYH14 Sema4DpPlexin-B1MetSEMA7AIntegrin alpha1beta1RHOB PLXNB3FYNNRP1 PLXNA2,PLXNA4RHOA ITGA1 CFL1Rnd1-GTPActive LIMK1SEMA4D SEMA3APLXND1FYNFES RHOC Sema3ANrp-1PlexinAFynpCdk5


Description

Semaphorins are a large family of cell surface and secreted guidance molecules divided into eight classes on the basis of their structures. They all have an N-terminal conserved sema domain. Semaphorins signal through multimeric receptor complexes that include other proteins such as plexins and neuropilins. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=373755

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Oinuma I, Katoh H, Harada A, Negishi M.; ''Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells.''; PubMed Europe PMC Scholia
  2. Raper JA.; ''Semaphorins and their receptors in vertebrates and invertebrates.''; PubMed Europe PMC Scholia
  3. Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, Hirata H, Iwahori K, Uchida J, Yasui T, Matsumoto M, Yoshida K, Yakura H, Pan C, Parnes JR, Kikutani H.; ''Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling.''; PubMed Europe PMC Scholia
  4. Dickson BJ.; ''Molecular mechanisms of axon guidance.''; PubMed Europe PMC Scholia
  5. Pasterkamp RJ, Verhaagen J.; ''Semaphorins in axon regeneration: developmental guidance molecules gone wrong?''; PubMed Europe PMC Scholia
  6. Sebbagh M, Hamelin J, Bertoglio J, Solary E, Bréard J.; ''Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner.''; PubMed Europe PMC Scholia
  7. Takegahara N, Takamatsu H, Toyofuku T, Tsujimura T, Okuno T, Yukawa K, Mizui M, Yamamoto M, Prasad DV, Suzuki K, Ishii M, Terai K, Moriya M, Nakatsuji Y, Sakoda S, Sato S, Akira S, Takeda K, Inui M, Takai T, Ikawa M, Okabe M, Kumanogoh A, Kikutani H.; ''Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.''; PubMed Europe PMC Scholia
  8. Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, Kaibuchi K.; ''GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity.''; PubMed Europe PMC Scholia
  9. Gatti A, Huang Z, Tuazon PT, Traugh JA.; ''Multisite autophosphorylation of p21-activated protein kinase gamma-PAK as a function of activation.''; PubMed Europe PMC Scholia
  10. Toyofuku T, Yoshida J, Sugimoto T, Zhang H, Kumanogoh A, Hori M, Kikutani H.; ''FARP2 triggers signals for Sema3A-mediated axonal repulsion.''; PubMed Europe PMC Scholia
  11. Leung T, Chen XQ, Manser E, Lim L.; ''The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton.''; PubMed Europe PMC Scholia
  12. Tanna AP, Johnson M.; ''Rho Kinase Inhibitors as a Novel Treatment for Glaucoma and Ocular Hypertension.''; PubMed Europe PMC Scholia
  13. Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A, Olson MF.; ''Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I.''; PubMed Europe PMC Scholia
  14. Billard C, Delaire S, Raffoux E, Bensussan A, Boumsell L.; ''Switch in the protein tyrosine phosphatase associated with human CD100 semaphorin at terminal B-cell differentiation stage.''; PubMed Europe PMC Scholia
  15. Swiercz JM, Worzfeld T, Offermanns S.; ''ErbB-2 and met reciprocally regulate cellular signaling via plexin-B1.''; PubMed Europe PMC Scholia
  16. Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K.; ''Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase).''; PubMed Europe PMC Scholia
  17. Uchida Y, Ohshima T, Sasaki Y, Suzuki H, Yanai S, Yamashita N, Nakamura F, Takei K, Ihara Y, Mikoshiba K, Kolattukudy P, Honnorat J, Goshima Y.; ''Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease.''; PubMed Europe PMC Scholia
  18. Aizawa H, Wakatsuki S, Ishii A, Moriyama K, Sasaki Y, Ohashi K, Sekine-Aizawa Y, Sehara-Fujisawa A, Mizuno K, Goshima Y, Yahara I.; ''Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse.''; PubMed Europe PMC Scholia
  19. Edwards DC, Sanders LC, Bokoch GM, Gill GN.; ''Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics.''; PubMed Europe PMC Scholia
  20. Gu C, Yoshida Y, Livet J, Reimert DV, Mann F, Merte J, Henderson CE, Jessell TM, Kolodkin AL, Ginty DD.; ''Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins.''; PubMed Europe PMC Scholia
  21. Ishida I, Kumanogoh A, Suzuki K, Akahani S, Noda K, Kikutani H.; ''Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses.''; PubMed Europe PMC Scholia
  22. Pasterkamp RJ, Kolodkin AL.; ''Semaphorin junction: making tracks toward neural connectivity.''; PubMed Europe PMC Scholia
  23. Herold C, Elhabazi A, Bismuth G, Bensussan A, Boumsell L.; ''CD100 is associated with CD45 at the surface of human T lymphocytes. Role in T cell homotypic adhesion.''; PubMed Europe PMC Scholia
  24. Sumi T, Matsumoto K, Nakamura T.; ''Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase.''; PubMed Europe PMC Scholia
  25. Nakamura F, Kalb RG, Strittmatter SM.; ''Molecular basis of semaphorin-mediated axon guidance.''; PubMed Europe PMC Scholia
  26. Garnock-Jones KP.; ''Ripasudil: first global approval.''; PubMed Europe PMC Scholia
  27. Li R, Soosairajah J, Harari D, Citri A, Price J, Ng HL, Morton CJ, Parker MW, Yarden Y, Bernard O.; ''Hsp90 increases LIM kinase activity by promoting its homo-dimerization.''; PubMed Europe PMC Scholia
  28. Toyofuku T, Yabuki M, Kamei J, Kamei M, Makino N, Kumanogoh A, Hori M.; ''Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1.''; PubMed Europe PMC Scholia
  29. Ikebe M, Koretz J, Hartshorne DJ.; ''Effects of phosphorylation of light chain residues threonine 18 and serine 19 on the properties and conformation of smooth muscle myosin.''; PubMed Europe PMC Scholia
  30. Ling K, Doughman RL, Firestone AJ, Bunce MW, Anderson RA.; ''Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions.''; PubMed Europe PMC Scholia
  31. Aurandt J, Vikis HG, Gutkind JS, Ahn N, Guan KL.; ''The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG.''; PubMed Europe PMC Scholia
  32. Swiercz JM, Kuner R, Offermanns S.; ''Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2.''; PubMed Europe PMC Scholia
  33. Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, Chedotal A, Winberg ML, Goodman CS, Poo M, Tessier-Lavigne M, Comoglio PM.; ''Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates.''; PubMed Europe PMC Scholia
  34. Artigiani S, Conrotto P, Fazzari P, Gilestro GF, Barberis D, Giordano S, Comoglio PM, Tamagnone L.; ''Plexin-B3 is a functional receptor for semaphorin 5A.''; PubMed Europe PMC Scholia
  35. Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, Watanabe N, Saito Y, Kakizuka A, Morii N, Narumiya S.; ''The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase.''; PubMed Europe PMC Scholia
  36. Bernard O.; ''Lim kinases, regulators of actin dynamics.''; PubMed Europe PMC Scholia
  37. Bernard O, Ganiatsas S, Kannourakis G, Dringen R.; ''Kiz-1, a protein with LIM zinc finger and kinase domains, is expressed mainly in neurons.''; PubMed Europe PMC Scholia
  38. Barberis D, Casazza A, Sordella R, Corso S, Artigiani S, Settleman J, Comoglio PM, Tamagnone L.; ''p190 Rho-GTPase activating protein associates with plexins and it is required for semaphorin signalling.''; PubMed Europe PMC Scholia
  39. Vikis HG, Li W, He Z, Guan KL.; ''The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner.''; PubMed Europe PMC Scholia
  40. Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K.; ''Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop.''; PubMed Europe PMC Scholia
  41. Araki S, Ito M, Kureishi Y, Feng J, Machida H, Isaka N, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T.; ''Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase.''; PubMed Europe PMC Scholia
  42. Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, Tamagnone L, Comoglio PM.; ''The semaphorin 4D receptor controls invasive growth by coupling with Met.''; PubMed Europe PMC Scholia
  43. Halloran MC, Wolman MA.; ''Repulsion or adhesion: receptors make the call.''; PubMed Europe PMC Scholia
  44. Oinuma I, Katoh H, Negishi M.; ''Semaphorin 4D/Plexin-B1-mediated R-Ras GAP activity inhibits cell migration by regulating beta(1) integrin activity.''; PubMed Europe PMC Scholia
  45. Ahmed A, Eickholt BJ.; ''Intracellular kinases in semaphorin signaling.''; PubMed Europe PMC Scholia
  46. Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, Matsuya T, Inagaki S.; ''Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors.''; PubMed Europe PMC Scholia
  47. Zhou Y, Gunput RA, Pasterkamp RJ.; ''Semaphorin signaling: progress made and promises ahead.''; PubMed Europe PMC Scholia
  48. Watanabe T, Hosoya H, Yonemura S.; ''Regulation of myosin II dynamics by phosphorylation and dephosphorylation of its light chain in epithelial cells.''; PubMed Europe PMC Scholia
  49. Sasaki Y, Cheng C, Uchida Y, Nakajima O, Ohshima T, Yagi T, Taniguchi M, Nakayama T, Kishida R, Kudo Y, Ohno S, Nakamura F, Goshima Y.; ''Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex.''; PubMed Europe PMC Scholia
  50. Chong C, Tan L, Lim L, Manser E.; ''The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity.''; PubMed Europe PMC Scholia
  51. Sturdivant JM, Royalty SM, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong MA.; ''Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma.''; PubMed Europe PMC Scholia
  52. Ueda K, Murata-Hori M, Tatsuka M, Hosoya H.; ''Rho-kinase contributes to diphosphorylation of myosin II regulatory light chain in nonmuscle cells.''; PubMed Europe PMC Scholia
  53. Mitsui N, Inatome R, Takahashi S, Goshima Y, Yamamura H, Yanagi S.; ''Involvement of Fes/Fps tyrosine kinase in semaphorin3A signaling.''; PubMed Europe PMC Scholia
  54. Koncina E, Roth L, Gonthier B, Bagnard D.; ''Role of semaphorins during axon growth and guidance.''; PubMed Europe PMC Scholia
  55. Ito Y, Oinuma I, Katoh H, Kaibuchi K, Negishi M.; ''Sema4D/plexin-B1 activates GSK-3beta through R-Ras GAP activity, inducing growth cone collapse.''; PubMed Europe PMC Scholia
  56. Pandey D, Pandey D, Goyal P, Bamburg JR, Siess W.; ''Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets.''; PubMed Europe PMC Scholia
  57. Ikebe M, Hartshorne DJ.; ''Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase.''; PubMed Europe PMC Scholia
  58. Deo RC, Schmidt EF, Elhabazi A, Togashi H, Burley SK, Strittmatter SM.; ''Structural bases for CRMP function in plexin-dependent semaphorin3A signaling.''; PubMed Europe PMC Scholia
  59. Schmidt EF, Strittmatter SM.; ''The CRMP family of proteins and their role in Sema3A signaling.''; PubMed Europe PMC Scholia
  60. Vikis HG, Li W, Guan KL.; ''The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding.''; PubMed Europe PMC Scholia
  61. Whitford KL, Ghosh A.; ''Plexin signaling via off-track and rho family GTPases.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114896view16:41, 25 January 2021ReactomeTeamReactome version 75
113342view11:41, 2 November 2020ReactomeTeamReactome version 74
112552view15:52, 9 October 2020ReactomeTeamReactome version 73
101466view11:33, 1 November 2018ReactomeTeamreactome version 66
101004view21:12, 31 October 2018ReactomeTeamreactome version 65
100540view19:46, 31 October 2018ReactomeTeamreactome version 64
100088view16:31, 31 October 2018ReactomeTeamreactome version 63
99638view15:02, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99241view12:44, 31 October 2018ReactomeTeamreactome version 62
94051view13:54, 16 August 2017ReactomeTeamreactome version 61
93678view11:30, 9 August 2017ReactomeTeamreactome version 61
86802view09:26, 11 July 2016ReactomeTeamreactome version 56
83271view10:36, 18 November 2015ReactomeTeamVersion54
81381view12:54, 21 August 2015ReactomeTeamVersion53
76850view08:07, 17 July 2014ReactomeTeamFixed remaining interactions
76554view11:54, 16 July 2014ReactomeTeamFixed remaining interactions
75887view09:54, 11 June 2014ReactomeTeamRe-fixing comment source
75587view10:42, 10 June 2014ReactomeTeamReactome 48 Update
74942view13:47, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74586view08:38, 30 April 2014ReactomeTeamReactome46
45022view18:42, 6 October 2011ThomasOntology Term : 'signaling pathway' added !
42123view21:58, 4 March 2011MaintBotAutomatic update
39933view05:57, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
ARHGAP35 ProteinQ9NRY4 (Uniprot-TrEMBL)
ARHGAP35ProteinQ9NRY4 (Uniprot-TrEMBL)
ARHGEF11 ProteinO15085 (Uniprot-TrEMBL)
ARHGEF12 ProteinQ9NZN5 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated ROCK

RhoA/B/C

GTP		ComplexREACT_19928 (Reactome)
Active LIMK1ComplexREACT_19790 (Reactome)
CD72 ProteinP21854 (Uniprot-TrEMBL)
CD72ProteinP21854 (Uniprot-TrEMBL)
CDK5 ProteinQ00535 (Uniprot-TrEMBL)
CDK5R1ProteinQ15078 (Uniprot-TrEMBL)
CFL1ProteinP23528 (Uniprot-TrEMBL)
CRMP's tetramersComplexREACT_19835 (Reactome)
CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
Cdk5 p35ComplexREACT_19863 (Reactome)
DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
DPYSL4 ProteinO14531 (Uniprot-TrEMBL)
DPYSL5 ProteinQ9BPU6 (Uniprot-TrEMBL)
ERBB2 ProteinP04626 (Uniprot-TrEMBL)
FARP2 PIP5KIgammaComplexREACT_19748 (Reactome)
FARP2 ProteinO94887 (Uniprot-TrEMBL)
FARP2ProteinO94887 (Uniprot-TrEMBL)
FES ProteinP07332 (Uniprot-TrEMBL)
FESProteinP07332 (Uniprot-TrEMBL)
FYNProteinP06241 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GSK3BProteinP49841 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
HSP-90ProteinREACT_19960 (Reactome)
HSP90AA1 ProteinP07900 (Uniprot-TrEMBL)
HSP90AB1 ProteinP08238 (Uniprot-TrEMBL)
ITGA1 ProteinP56199 (Uniprot-TrEMBL)
ITGB1 ProteinP05556 (Uniprot-TrEMBL)
Integrin alpha1beta1ComplexREACT_14015 (Reactome)
LARG and PDZ-RhoGEFProteinREACT_20012 (Reactome)
LIM Kinases, phosphorylatedProteinREACT_19576 (Reactome)
LIM KinasesProteinREACT_20207 (Reactome)
LIMK1ProteinP53667 (Uniprot-TrEMBL)
MET ProteinP08581 (Uniprot-TrEMBL)
MYH10 ProteinP35580 (Uniprot-TrEMBL)
MYH11 ProteinP35749 (Uniprot-TrEMBL)
MYH14 ProteinQ7Z406 (Uniprot-TrEMBL)
MYH9 ProteinP35579 (Uniprot-TrEMBL)
MYL12BProteinO14950 (Uniprot-TrEMBL)
MYL6 ProteinP60660 (Uniprot-TrEMBL)
MYL9 ProteinP24844 (Uniprot-TrEMBL)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NRP1

PlexinA1-4 FARP2

FYN		ComplexREACT_20390 (Reactome)
NRP1

PlexinA1-4

FYN		ComplexREACT_20319 (Reactome)
NRP1 ProteinO14786 (Uniprot-TrEMBL)
NRP1ProteinO14786 (Uniprot-TrEMBL)
PAK homodimerComplexREACT_19479 (Reactome)
PAK1 ProteinQ13153 (Uniprot-TrEMBL)
PAK2ProteinQ13177 (Uniprot-TrEMBL)
PAKProteinREACT_19640 (Reactome)
PIP5K1C ProteinO60331 (Uniprot-TrEMBL)
PIP5K1gamma Talin-1ComplexREACT_19891 (Reactome)
PLXNA1

TREM2

DAP12		ComplexREACT_20126 (Reactome)
PLXNA1 ProteinQ9UIW2 (Uniprot-TrEMBL)
PLXNA2,PLXNA4ProteinREACT_20091 (Reactome)
PLXNA2ProteinO75051 (Uniprot-TrEMBL)
PLXNA3 ProteinP51805 (Uniprot-TrEMBL)
PLXNA4 ProteinQ9HCM2 (Uniprot-TrEMBL)
PLXNB1 ProteinO43157 (Uniprot-TrEMBL)
PLXNB3 ProteinQ9ULL4 (Uniprot-TrEMBL)
PLXNB3ProteinQ9ULL4 (Uniprot-TrEMBL)
PLXNC1 ProteinO60486 (Uniprot-TrEMBL)
PLXNC1ProteinO60486 (Uniprot-TrEMBL)
PLXND1 ProteinQ9Y4D7 (Uniprot-TrEMBL)
PLXND1ProteinQ9Y4D7 (Uniprot-TrEMBL)
PTPRC ProteinP08575 (Uniprot-TrEMBL)
PTPRCProteinP08575 (Uniprot-TrEMBL)
Phospho-activated smooth muscle/non-muscle myosin 2ComplexREACT_19704 (Reactome) Nonmuscle myosin II (NMM2) is an actin-based motor protein that plays a crucial role in a variety of cellular processes, including cell migration, polarity formation, and cytokinesis. NMM2 consists of two myosin heavy chains encoded by MYH9, MYH10 or MYH14 (NMHC-IIA, B and C), two copies of MYL6 essential light chain protein, and two regulatory light chains (MRLCs), MYL9 and MYLC2B. Myosin II activity is stimulated by phosphorylation of MRLC. Diphosphorylation at Thr-19 and Ser-20 increases both actin-activated Mg2+ ATPase activity and the stability of myosin II filaments; monophosphorylation at Ser-20 is less effective. Kinases responsible for the phosphorylation include myosin light chain kinase (MLCK), ROCK kinase, citron kinase, myotonic dystrophy kinase-related CDC42-binding protein kinase, and Zipper-interacting protein (ZIP) kinase. ROCK activity has been shown to regulate MRLC phosphorylation by directly mono- (Amano et al., 1996) or di- (Ueda et al., 2002) phosphorylating MRLC.
PiMetaboliteCHEBI:18367 (ChEBI)
Plexin-A1-4 FYNComplexREACT_19507 (Reactome)
Plexin-B1 ErbB2ComplexREACT_19954 (Reactome)
Plexin-B1 MetComplexREACT_19866 (Reactome)
R-Ras-GDPComplexREACT_20329 (Reactome)
R-Ras-GTPComplexREACT_20411 (Reactome)
RAC1 ProteinP63000 (Uniprot-TrEMBL)
RAC1-GDPComplexREACT_22018 (Reactome)
RAC1-GTPComplexREACT_21594 (Reactome)
RHOA ProteinP61586 (Uniprot-TrEMBL)
RHOB ProteinP62745 (Uniprot-TrEMBL)
RHOC ProteinP08134 (Uniprot-TrEMBL)
RND1 ProteinQ92730 (Uniprot-TrEMBL)
ROCK1ProteinQ13464 (Uniprot-TrEMBL)
ROCK2 ProteinO75116 (Uniprot-TrEMBL)
ROCKProteinREACT_20281 (Reactome) ROCK I (alternatively called ROK ?) and ROCK II (also known as Rho kinase or ROK ?) were originally isolated as RhoA-GTP interacting proteins. The kinase domains of ROCK I and ROCK II are 92% identical, and so far there is no evidence that they phosphorylate different substrates. RhoA, RhoB, and RhoC associate with and activate ROCK but other GTP-binding proteins can be inhibitors, e.g. RhoE, Rad and Gem. PDK1 kinase promotes ROCK I activity not through phosphorylation but by blocking RhoE association. PLK1 can phosphorylate ROCK II and this enhances the effect of RhoA. Arachidonic acid can activate ROCK independently of Rho.
RRAS ProteinP10301 (Uniprot-TrEMBL)
RhoA ComplexREACT_13852 (Reactome)
RhoA ComplexREACT_14306 (Reactome)
RhoA,B,C GDPComplexREACT_20118 (Reactome)
RhoA/B/C GTPComplexREACT_19589 (Reactome)
Rnd1-GTPComplexREACT_20300 (Reactome)
SEMA3A PLXND1ComplexREACT_20367 (Reactome)
SEMA3A ProteinQ14563 (Uniprot-TrEMBL)
SEMA3E ProteinO15041 (Uniprot-TrEMBL)
SEMA3EProteinO15041 (Uniprot-TrEMBL)
SEMA4A PLXND1ComplexREACT_19803 (Reactome)
SEMA4A ProteinQ9H3S1 (Uniprot-TrEMBL)
SEMA4AProteinQ9H3S1 (Uniprot-TrEMBL)
SEMA4D CD72ComplexREACT_20194 (Reactome)
SEMA4D PTPRCComplexREACT_19862 (Reactome)
SEMA4D

pPlexin-B1

ErbB2 complex		ComplexREACT_20256 (Reactome)
SEMA4D ProteinQ92854 (Uniprot-TrEMBL)
SEMA4D dimerComplexREACT_19817 (Reactome)
SEMA4DProteinQ92854 (Uniprot-TrEMBL)
SEMA5A PLXNB3ComplexREACT_19434 (Reactome)
SEMA5A ProteinQ13591 (Uniprot-TrEMBL)
SEMA5AProteinQ13591 (Uniprot-TrEMBL)
SEMA6A PLXNA2,PLXNA4ComplexREACT_19923 (Reactome)
SEMA6A ProteinQ9H2E6 (Uniprot-TrEMBL)
SEMA6AProteinQ9H2E6 (Uniprot-TrEMBL)
SEMA6D

PLXNA1 TREM2

DAP12		ComplexREACT_19554 (Reactome)
SEMA6D ProteinQ8NFY4 (Uniprot-TrEMBL)
SEMA6DProteinQ8NFY4 (Uniprot-TrEMBL)
SEMA7A Integrin alpha1beta1ComplexREACT_20443 (Reactome)
SEMA7A PLXNC1ComplexREACT_20419 (Reactome)
SEMA7A ProteinO75326 (Uniprot-TrEMBL)
SEMA7AProteinO75326 (Uniprot-TrEMBL)
Sema3A

NP-1 Plexin-A Fes

CRMP		ComplexREACT_20015 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		ComplexREACT_19958 (Reactome)
Sema3A

Nrp-1 Plexin A

Fyn		ComplexREACT_19816 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		ComplexREACT_19706 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		ComplexREACT_20425 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn

pCdk5		ComplexREACT_20429 (Reactome)
Sema3A

Nrp-1 PlexinA

Fyn		ComplexREACT_20413 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

PAK		ComplexREACT_20083 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

pPAK		ComplexREACT_19495 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes Rac-1-GTP

Rnd1		ComplexREACT_19802 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes

Rac-1-GTP		ComplexREACT_20187 (Reactome)
Sema3A dimerComplexREACT_19939 (Reactome)
Sema4D

Plexin-B1 Rac-Rnd1

LARG/PDZ-RhoGEF		ComplexREACT_20349 (Reactome)
Sema4D

Plexin-B1 p190RhoGAP Rac

Rnd1		ComplexREACT_19579 (Reactome)
Sema4D

pPlexin-B1 ErbB2 Rac1

Rnd1		ComplexREACT_19890 (Reactome)
Sema4D

pPlexin-B1 Met

RAC1-GTP		ComplexREACT_20028 (Reactome)
Sema4D

pPlexin-B1 Met

Rnd1		ComplexREACT_19721 (Reactome)
Sema4D

pPlexin-B1

Met		ComplexREACT_19905 (Reactome)
Smooth muscle/non-muscle myosin IIComplexREACT_19969 (Reactome) Class 2 myosins are a set of protein complexes that bind actin and hydrolyse ATP, acting as molecular motors. They consist of two myosin heavy chains , two essential light chains and two regulatory light chains (MRLCs). Smooth muscle and non-muscle myosin isoforms are a subset of Class 2 myosin complexes. The nomenclature for isoforms is misleading, as non-muscle isoforms can be found in smooth muscle. The 4 smooth muscle isoforms all have heavy chains encoded by MYH11. The non-muscle isoforms have heavy chains encoded by MYH9, MYH10 or MYH14 (NMHC-IIA, B and C). The essential light chain (LC17) common to smooth and non-muscle isoforms is encoded by MYL6. The regulatory light chain (LC20) is encoded by either MYL9, giving a slightly more basic protein that is referred to as the smooth muscle LC20 isoform, and MRLC2, giving a more acidic isoform referred to as the non-muscle LC20 isoform. Class 2 myosins play a crucial role in a variety of cellular processes, including cell migration, polarity formation, and cytokinesis.
TLN1 ProteinQ9Y490 (Uniprot-TrEMBL)
TLN1ProteinQ9Y490 (Uniprot-TrEMBL)
TREM2 ProteinQ9NZC2 (Uniprot-TrEMBL)
TYROBP ProteinO43914 (Uniprot-TrEMBL)
p-S,T508-LIMK1 ProteinP53667 (Uniprot-TrEMBL)
p-S141,T402-PAK2ProteinQ13177 (Uniprot-TrEMBL)
p-S144,T423-PAK1 ProteinQ13153 (Uniprot-TrEMBL)
p-S3-CFL1 ProteinP23528 (Uniprot-TrEMBL)
p-S522-CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
p-S522-DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
p-S522-DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
p-S534-DPYSL5 ProteinQ9BPU6 (Uniprot-TrEMBL)
p-S544-DPYSL4 ProteinO14531 (Uniprot-TrEMBL) CRMP-3 does not have the conserved serine 522 and based on similarity serine 544 may be phosphorylated upon sema3A stimulation.
p-T19,S20-MYL12BProteinO14950 (Uniprot-TrEMBL)
p-T19,S20-MYL9 ProteinP24844 (Uniprot-TrEMBL)
p-T508-LIMK1 ProteinP53667 (Uniprot-TrEMBL)
p-T508-LIMK1ProteinP53667 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
p-Y-CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
p-Y-DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
p-Y-DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
p-Y-DPYSL4 ProteinO14531 (Uniprot-TrEMBL) CRMP-3 does not have the conserved serine 522 and based on similarity serine 544 may be phosphorylated upon sema3A stimulation.
p-Y-DPYSL5 ProteinQ9BPU6 (Uniprot-TrEMBL)
p-Y-PLXNA1 ProteinQ9UIW2 (Uniprot-TrEMBL)
p-Y-PLXNA2ProteinO75051 (Uniprot-TrEMBL)
p-Y-PLXNA3 ProteinP51805 (Uniprot-TrEMBL)
p-Y-PLXNA4 ProteinQ9HCM2 (Uniprot-TrEMBL)
p-Y-PLXNB1 ProteinO43157 (Uniprot-TrEMBL)
p-Y15-CDK5 ProteinQ00535 (Uniprot-TrEMBL)
pCofilin Active LIMK-1ComplexREACT_20103 (Reactome)
pLIMK dimer HSP-90ComplexREACT_19543 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_19161 (Reactome)
ADPArrowREACT_19168 (Reactome)
ADPArrowREACT_19191 (Reactome)
ADPArrowREACT_19197 (Reactome)
ADPArrowREACT_19221 (Reactome)
ADPArrowREACT_19276 (Reactome)
ADPArrowREACT_19282 (Reactome)
ADPArrowREACT_19285 (Reactome)
ADPArrowREACT_19321 (Reactome)
ADPArrowREACT_19381 (Reactome)
ADPArrowREACT_19393 (Reactome)
ADPArrowREACT_19398 (Reactome)
ADPArrowREACT_19420 (Reactome)
ARHGAP35REACT_19356 (Reactome)
ATPREACT_19161 (Reactome)
ATPREACT_19168 (Reactome)
ATPREACT_19191 (Reactome)
ATPREACT_19197 (Reactome)
ATPREACT_19221 (Reactome)
ATPREACT_19276 (Reactome)
ATPREACT_19282 (Reactome)
ATPREACT_19285 (Reactome)
ATPREACT_19321 (Reactome)
ATPREACT_19381 (Reactome)
ATPREACT_19393 (Reactome)
ATPREACT_19398 (Reactome)
ATPREACT_19420 (Reactome)
Activated ROCK

RhoA/B/C

GTP		REACT_19191 (Reactome)
Activated ROCK

RhoA/B/C

GTP		REACT_19282 (Reactome)
Active LIMK1ArrowREACT_19168 (Reactome)
Active LIMK1REACT_19276 (Reactome)
CD72REACT_19336 (Reactome)
CFL1REACT_19276 (Reactome)
CRMP's tetramersREACT_19161 (Reactome)
CRMP's tetramersREACT_19285 (Reactome)
Cdk5 p35REACT_19393 (Reactome)
FARP2 PIP5KIgammaArrowREACT_19403 (Reactome)
FARP2ArrowREACT_19173 (Reactome)
FARP2REACT_19128 (Reactome)
FARP2REACT_19363 (Reactome)
FARP2REACT_19403 (Reactome)
FESREACT_19420 (Reactome)
GDPArrowREACT_19137 (Reactome)
GDPArrowREACT_19363 (Reactome)
GSK3BREACT_19321 (Reactome)
GTPREACT_19137 (Reactome)
GTPREACT_19363 (Reactome)
HSP-90ArrowREACT_19168 (Reactome)
HSP-90REACT_19307 (Reactome)
Integrin alpha1beta1REACT_19139 (Reactome)
LARG and PDZ-RhoGEFREACT_19153 (Reactome)
LIM Kinases, phosphorylatedArrowREACT_19282 (Reactome)
LIM KinasesREACT_19282 (Reactome)
LIMK1REACT_19221 (Reactome)
NRP1

PlexinA1-4 FARP2

FYN		REACT_19173 (Reactome)
NRP1

PlexinA1-4

FYN		REACT_19368 (Reactome)
NRP1REACT_19128 (Reactome)
PAK homodimerREACT_19269 (Reactome)
PAKArrowREACT_19269 (Reactome)
PIP5K1gamma Talin-1REACT_19403 (Reactome)
PLXNA1

TREM2

DAP12		REACT_19177 (Reactome)
PLXNA2,PLXNA4REACT_19345 (Reactome)
PLXNB3REACT_19322 (Reactome)
PLXNC1REACT_19190 (Reactome)
PLXND1REACT_19273 (Reactome)
PLXND1REACT_19408 (Reactome)
PTPRCREACT_19295 (Reactome)
Phospho-activated smooth muscle/non-muscle myosin 2ArrowREACT_19191 (Reactome)
PiArrowREACT_19117 (Reactome)
PiArrowREACT_19120 (Reactome)
PiArrowREACT_19242 (Reactome)
Plexin-A1-4 FYNREACT_19128 (Reactome)
Plexin-B1 ErbB2REACT_19381 (Reactome)
Plexin-B1 MetREACT_19398 (Reactome)
R-Ras-GDPArrowREACT_19117 (Reactome)
R-Ras-GDPArrowREACT_19120 (Reactome)
RAC1-GDPREACT_19363 (Reactome)
RAC1-GTPArrowREACT_19363 (Reactome)
RAC1-GTPREACT_19160 (Reactome)
RAC1-GTPREACT_19354 (Reactome)
REACT_19117 (Reactome) Plexin-A's are GAPs for the Ras family GTPase R-Ras. On stimulation with Rnd-1, plexin-A directly and specifically down regulates R-Ras activity. R-Ras activity is critical for PI3K activation and ECM-mediated beta1 integrin activation and cell migration. Inactivation of R-Ras by Sema3A/Plexin-A1 reduces integrin-mediated adhesions. It has been suggested that the final step in the Sema3A repulsive signaling pathway is inhibition of integrin activity. Reduced integrin activity allows detachment from the substratum and subsequent cell retraction.
REACT_19120 (Reactome) Plexin-B1 functions as an R-Ras GTPase-activating protein (GAP) and directly and specifically down regulates R-Ras activity in response to Sema4D, inducing growth cone collapse. R-Ras inactivation promotes PI3K and Akt inactivation followed by GSK-3beta activation and CRMP inactivation. R-Ras inactivation also inhibits cell migration by regulating beta1 integrin activity.

REACT_19128 (Reactome) The best characterized receptors for mediating semaphorin signaling are members of the neuropilin and plexin families of transmembrane proteins. Neuropilins form complexes with Plexin-A which in turn can act as a signaling moiety. Also, when complexed with neuropilin-1, plexin-A1 can associate directly with the FERM domain containing guanine nucleotide exchange factor (GEF) FARP2. FARP2 exerts GEF activity for Rac but not Cdc42 and Rho.
REACT_19137 (Reactome) The RhoGEFs LARG and PDZ-RhoGEF complexed with Plexin-B1 stimulate the exchange of GDP for GTP on RhoA through their DH and PH domains.
REACT_19139 (Reactome) Sema7A has a RGD-motif in the extracellular region and interacts with alpha1beta1 integrin in both olfactory nerves and monocytes/macrophages. This interaction stimulates cytokine production in monocytes and macrophages, and is critical for the effector phase of the inflammatory immune response.
REACT_19153 (Reactome) Plexin-B1 activates RhoA and induces growth cone collapse and and cytoskeletal reorganization through Rho-specific guanine nucleotide exchange factors PDZ-RhoGEF and leukemia-associated RhoGEF (LARG). Plexin-B1 directly interacts with PDZ-RhoGEF through its c-terminal PDZ domain binding motif. It has been suggested that Rnd1, which binds to the cytoplasmic part of plexin-B1, can promote the interaction between plexin-B1 and PDZ-RhoGEF. The PDZ domain of LARG is directly involved in the interaction with the c-terminal sequence of Plexin-B1.
REACT_19160 (Reactome) Active Rac1 associates directly with Plexin-A1 in the linker region separating Plexin-A1's cytoplasmic GAP domains. Rac1 association relieves an inhibitory intramolecular interaction between the two Plexin-A1 GAP domains C1 and C2.
REACT_19161 (Reactome) Fes bound to Plexin-A is able to phosphorylate all five forms of CRMP, though neither specific sites nor the consequence of tyrosine phosphorylation in CRMP's have yet been investigated directly.
REACT_19168 (Reactome) Binding of Hsp90 to the LIMK proteins protects them from degradation and promotes their dimer formation and transphosphorylation. It is estimated that LIMK1 contains at least 5 phospho-amino acids primarily phospho-serines, in its kinase domain. The positions of these serine residues are not known. Transphosphorylation of these serine residues in LIMK1 increases its stability.
REACT_19173 (Reactome) Although neuropilin-1 is required for Sema-3A action, it is incapable of transmitting a Sema-3A signal to the growth cone interior. The function of Sema-3A is mediated by Plexins. Sema-3A binds with high affinity to Plexin when the latter is complexed with Neuropilin-1.
Plexin-A1 is known to act as an R-Ras GAP (GTPase activating protein) when bound by Sema-3A. Plexin's GAP activity is regulated by FARP2 mediated Rac1 activation. Sema-3A binding to neuropilin-1/Plexin-A1 seems to induce a conformational change of plexin-A1 necessary for releasing FARP2. This suggests that neuropilin1 is required not only for ligand binding, but also for signaling, by modulating the interaction of FARP2 with plexin-A1.
REACT_19177 (Reactome) Plexin-A1 is a receptor for the transmembrane semaphorin, Sema6D. Plexin-A1 associates with the triggering receptor expressed on myeloid cells-2 (Trem-2), linking semaphorin-signalling to the immuno-receptor tyrosine-based activation motif (ITAM)-bearing adaptor protein, DAP12.
REACT_19190 (Reactome) Sema7A signals through two unrelated receptors, an RGD-dependent alpha1beta1-integrin and a member of the plexin family, plexinC1. Sema7A-plexinC1 interactions have been implicated in immune system function and also participate in neuronal network formation.
REACT_19191 (Reactome) Nonmuscle myosin II (NMM2) is an actin-based motor protein that plays a crucial role in a variety of cellular processes, including cell migration, polarity formation, and cytokinesis. NMM2 consists of two myosin heavy chains encoded by MYH9, MYH10 or MYH14 (NMHC-IIA, B and C), two copies of MYL6 essential light chain protein, and two regulatory light chains (MRLCs), MYL9 and MYLC2B. Myosin II activity is stimulated by phosphorylation of MRLC. Diphosphorylation at Thr-19 and Ser-20 increases both actin-activated Mg2+ ATPase activity and the stability of myosin II filaments; monophosphorylation at Ser-20 is less effective. Kinases responsible for the phosphorylation include myosin light chain kinase (MLCK), ROCK kinase, citron kinase, myotonic dystrophy kinase-related CDC42-binding protein kinase, and Zipper-interacting protein (ZIP) kinase. ROCK activity has been shown to regulate MRLC phosphorylation by directly mono- (Amano et al., 1996) or di- (Ueda et al., 2002) phosphorylating MRLC.
REACT_19197 (Reactome) PAK is autophosphorylated at several sites but S-144 flanking the kinase inhibitor region and T-423 (S-141/T-402 in PAK-gamma) within the catalytic domain are the two conserved sites that regulate the catalytic activity.
REACT_19221 (Reactome) LIM-kinase is responsible for the tight regulation of the activity of cofilin (a protein that depolymerizes actin filaments) and thus maintains the balance between actin assembly and disassembly. LIMK is one of the downstream targets of PAK1 and is activated through phosphorylation by PAK1 on T508 within its activation loop.
REACT_19242 (Reactome) p190RhoGAP complexed with Plexin-B1 stimulates GTP hydrolysis by RhoA. The resulting lower levels of Rho-GTP may account for F-actin depolymerization and cytoskeletal rearrangements.
REACT_19269 (Reactome) Plexin-bound Rac1 binds to and stimulates the kinase activity of PAK. PAK dimers are arranged in head-to-tail fashion, in which the catalytic domain binds the kinase inhibitory (KI) domain and is supported by associated PAK-interacting exchange factor (PIX) dimers. Upon Rac1 binding the kinase undergoes conformational change that allows autophosphorylation. Phosphorylation of serine residues disables the KI-domain-kinase interaction and thereby reduces the affinity of PIX.
REACT_19273 (Reactome) SEMA3E binds to neither neuropilin but instead binds directly to plexin-D1. This interaction controls endothelial cell positioning and the patterning of the developing vasculature.
REACT_19276 (Reactome) Cofilin is a member of the ADF (actin-depolymerizing factor) protein family, that is involved in regulating actin dynamics in the growth cone. It binds to actin in a one-to-one molar ratio, and stimulates both the severing of actin filaments and depolymerization of actin subunits from the actin filament end.
Activated LIMK phosphorylates cofilin on conserved serine 3 (Ser3/S3), located near the actin binding site. After phosphorylation cofilin is inactive and looses its affinity for actin and releases from G-actin monomers. Now the ADP-actin monomers are free and can exchange ADP with cytoplasmic ATP and they are ready for reincorporation at the barbed end of the a growing filament.
REACT_19282 (Reactome) ROCK I phosphorylates LIMK1 at Thr508 and LIMK2 at Thr505, enhancing the ability of LIMKs to phosphorylate cofilin.
REACT_19285 (Reactome) Cdk5:p35 complex is associated with Plexin-A through the actived form of Fyn. CRMPs are the downstream substrates for Cdk5. Cdk5 phosphorylates serine 522 of CRMPs. Phosphorylation of CRMPs mediates the Sema3A induced growth cone collapse.
Collapsin response mediator proteins (CRMPs) are five homologous cytosolic phosphoproteins (CRMP1–5) involved in neuronal differentiation and axonal guidance. These members oligomerize and exist as tetramers.
REACT_19295 (Reactome) SEMA4D also associates with CD45, a cell surface protein tyrosine phosphatase (PTP) considered a key molecule in the T-cell receptor (TCR) activation process.
REACT_19307 (Reactome) After phosphorylation on Thr 508, LIMK undergoes homodimerization. Homodimer formation is promoted by the binding of heat shock protein 90 (Hsp90) to a short sequence in the kinase domain of LIMKs. LIMKs are further phosphorylated after homodimer formation and transphosphorylation of the kinase domain.
REACT_19321 (Reactome) The phosphorylation of CRMPs at Ser522 allows the subsequent phosphorylation of CRMP1, CRMP2 and CRMP4 at Ser518, Thr509, and Thr514 mediated by serine/threonine kinase GSK3beta. Phosphorylation of CRMP by GSK3beta results in decreased CRMP affinity for beta-tubulin and changes in microtubule dynamics.
REACT_19322 (Reactome) Sema5s have been implicated in invasive growth, vascular patterning and axon guidance. Plexin-B3 is the specific and high-affinity receptor for Sema5A, and their interaction triggers the collapsing response.
REACT_19336 (Reactome) In the immune system, Sema4D/CD100 binds CD72 to mediate B-cell-B-cell, B-cell-T-cell and T-cell-dendritic cell interactions and there by regulates B-cell and T-cell activation. In B-cells, this interaction directs the dissociation of SHP-1 from the CD72 cytoplasmic domain and enhances their activation.

REACT_19337 (Reactome) Binding of Sema3A to the Neuropilin-1-Plexin-A receptor complex results in the recruitment of Rnd1 to the cytoplasmic linker region of Plexin-A. Rnd1 activates the cytoplasmic GTPase signaling domain of Plexin-A.
REACT_19345 (Reactome) Sema6A binds plexinA2 and plexinA4 to establish lamina-restricted axon projection in the hippocampus.
REACT_19354 (Reactome) The cytoplasmic tails of plexins have two domains, C1 and C2, which are highly conserved and act as GAP for small GTPases like Rac1. Active Rac1 binds directly to a binding domain of Plexin-B1 in the linker region between C1 and C2. The functional consequence of the plexin-B1/Rac interaction is not understood but this binding might sequester Rac1 away from p21-activated kinase (PAK). Plexin-B1 can compete with PAK for binding to active Rac and this competition results in the ability of plexin-B1 to inhibit Rac-induced PAK activation.
REACT_19356 (Reactome) Plexin-B1 can mediate inhibition of RhoA via the Sema4D-dependent recruitment of p190RhoGAP into the semaphorin receptor complex.
REACT_19363 (Reactome) Sema3A-mediated dissociation of FARP2 from Plexin-A is followed by activation of Rac1 by the GEF activity of released FARP2.
FARP2 is critical for Sema3A-mediated axonal repulsion through two independent downstream signaling pathways. Sema3A mediated disassociation of FARP2 from Plexin-A is followed by activation of Rac by GEF activity of released FARP2, binding of Rnd1 to plexin-A and down regulation of R-Ras by GAP activity of plexin-A.
REACT_19368 (Reactome) PlexinA1 and A2 are constitutively bound to the src family tyrosine kinase, Fyn. Stimulation with Sema3A causes Fyn activation and leads to the recruitment of Cdk5 into the complex.
REACT_19381 (Reactome) Sema4D binds Plexin-B1 to induce repulsive or attractive effects in neuronal and nonneuronal cells. Plexins constitute a large family of transmembrane proteins that function as receptors for semaphorins and their interaction governs cell adhesion and migration in a variety of tissues. All B-class plexins can interact with the receptor tyrosine kinases Met and ErbB2. Upon binding of Sema4D to plexin-B1, the kinase activity of ErbB2 is increased resulting in tyrosine phosphorylation of both Plexin-B1 and ErbB2. ErbB2 has been shown to mediate Sema4D-induced growth cone collapse in hippocampal neurons by the activation of RhoA via plexinB1 and PDZRhoGEF/LARG.
Sequence alignment reveals the presence of 13 conserved tyrosine residues (highly conserved sites 1918, 1953, 2038) but the specific tyrosine residues phosphorylated in the cytoplasmic domain of plexins in response to semaphorin stimulation have not yet been identified.
REACT_19382 (Reactome) Rnd1 is constitutively active and stably associates with Plexin-B1 and regulates the R-Ras GAP activity of the C1 and C2 domains of the Plexin-B1 cytoplasmic tail. These domains interact with each other and in this closed conformation cannot associate with active R-Ras-GTP. Rnd1 binds to the region between C1 and C2 domains and disrupts this interaction, allowing the receptor to associate with GTP-bound R-Ras.
REACT_19389 (Reactome) Rho-associated, coiled-coil containing protein kinases (ROCKs) are primarily known as downstream effectors of Rho, but they can also be activated by arachidonic acid, which binds to the pleckstrin homology domain, releasing an autoinhibitory loop within ROCK allowing catalytic activity. Multiple targets of ROCK contribute to the stabilization of actin filaments and the generation of actin-myosin contractile force.
REACT_19393 (Reactome) Cdk5:p53 complex is recruited to the growth cone by associating with active Fyn. Fyn promotes the kinase activity of Cdk5 by phosphorylating Cdk5 on tyrosine residue 15. Activation of Cdk5 by Fyn via Tyr15 phosphorylation might facilitate suppression of Rac-PAK signaling downstream of PlexinA.
Cyclin-dependent kinase 5 (Cdk5), a member of the serine/threonine kinase Cdk family, is complexed with p35 a neuron specific activator of Cdk5. The complex Cdk5:p35 is required for neurite outgrowth and cortical lamination.
REACT_19398 (Reactome) Sema4D binds Plexin-B1 to induce repulsive or attractive effects in neuronal and nonneuronal cells. Plexins constitute a large family of transmembrane proteins that function as receptors for semaphorins and their interaction governs cell adhesion and migration in a variety of tissues. All B-class plexins can interact with the receptor tyrosine kinases Met and ErbB2. The binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of Met, leading to the phosphorylation of both Plexin-B1 and Met. The phosphorylation of the plexin-B1/Met complex induced by Sema4D is crucial for epithelial cell migration and invasive growth. Sequence alignment reveals the presence of 13 conserved tyrosine residues (highly conserved sites 1918, 1953, 2038), but the specific tyrosine residues phosphorylated in the cytoplasmic domain of plexins in response to semaphorin stimulation have not yet been identified.
REACT_19403 (Reactome) Sema3A also mediates integrin inhibition by a mechanism involving PIPKI gamma 661, a phosphatidylinositol kinase that participates in integrin mediated focal adhesion assembly. The binding of talin to beta-integrin is required for integrin activation and is strengthened by PtdIns(4,5)P(2). PIPKI gamma 661, an enzyme that makes PtdIns(4,5)P(2), is targeted to focal adhesions by an association with talin. Sema3A induced dissociation of FARP2 from Plexin-A1 stimulates an interaction between FARP2 and PIPKI gamma 661. FARP2 inhibits PIPK gamma 661's kinase activity, and thus inhibits integrin mediated adhesion.
REACT_19408 (Reactome) Sema4A binds plexinD1 to inhibit angiogenesis. Sema4A–plexinD1 interactions modulate VEGF-mediated endothelial cell migration and proliferation at the intracellular level by suppressing VEGF–VEGFR2-induced activation of Rac1, Akt and integrins.
REACT_19420 (Reactome) Sema3A binding to Neuropilin-1:Plexin-A complex results in conformational change of plexin-A and this conformational change permits Fes nonreceptor tyrosine kinase to bind and phosphorylate Plexin-A. The specific tyrosine residues phosphorylated in the cytoplasmic domain of plexins in response to semaphorin stimulation have not yet been identified.
ROCKREACT_19389 (Reactome)
RhoA ArrowREACT_19242 (Reactome)
RhoA,B,C GDPREACT_19137 (Reactome)
RhoA/B/C GTPArrowREACT_19137 (Reactome)
RhoA/B/C GTPREACT_19389 (Reactome)
Rnd1-GTPREACT_19337 (Reactome)
Rnd1-GTPREACT_19382 (Reactome)
SEMA3EREACT_19273 (Reactome)
SEMA4AREACT_19408 (Reactome)
SEMA4D

pPlexin-B1

ErbB2 complex		ArrowREACT_19381 (Reactome)
SEMA4D dimerREACT_19381 (Reactome)
SEMA4D dimerREACT_19398 (Reactome)
SEMA4DREACT_19295 (Reactome)
SEMA4DREACT_19336 (Reactome)
SEMA5AREACT_19322 (Reactome)
SEMA6AREACT_19345 (Reactome)
SEMA6DREACT_19177 (Reactome)
SEMA7AREACT_19139 (Reactome)
SEMA7AREACT_19190 (Reactome)
Sema3A

NP-1 Plexin-A Fes

CRMP		ArrowREACT_19161 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		ArrowREACT_19420 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		REACT_19160 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		REACT_19161 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		REACT_19420 (Reactome)
Sema3A

Nrp-1 Plexin A

Fyn		ArrowREACT_19173 (Reactome)
Sema3A

Nrp-1 Plexin A

Fyn		REACT_19420 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		ArrowREACT_19285 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		ArrowREACT_19321 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		REACT_19321 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn

pCdk5		ArrowREACT_19393 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn

pCdk5		REACT_19285 (Reactome)
Sema3A

Nrp-1 PlexinA

Fyn		REACT_19393 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

PAK		ArrowREACT_19269 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

PAK		REACT_19197 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

pPAK		ArrowREACT_19197 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

pPAK		REACT_19221 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes Rac-1-GTP

Rnd1		REACT_19117 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes

Rac-1-GTP		REACT_19269 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes

Rac-1-GTP		REACT_19337 (Reactome)
Sema3A dimerREACT_19173 (Reactome)
Sema3A dimerREACT_19368 (Reactome)
Sema4D

Plexin-B1 Rac-Rnd1

LARG/PDZ-RhoGEF		REACT_19137 (Reactome)
Sema4D

Plexin-B1 p190RhoGAP Rac

Rnd1		REACT_19242 (Reactome)
Sema4D

pPlexin-B1 ErbB2 Rac1

Rnd1		REACT_19153 (Reactome)
Sema4D

pPlexin-B1 Met

Rnd1		REACT_19120 (Reactome)
Sema4D

pPlexin-B1 Met

Rnd1		REACT_19356 (Reactome)
Sema4D

pPlexin-B1

Met		ArrowREACT_19398 (Reactome)
Sema4D

pPlexin-B1

Met		REACT_19354 (Reactome)
Sema4D

pPlexin-B1

Met		REACT_19382 (Reactome)
Smooth muscle/non-muscle myosin IIREACT_19191 (Reactome)
TLN1ArrowREACT_19403 (Reactome)
p-T508-LIMK1ArrowREACT_19221 (Reactome)
p-T508-LIMK1REACT_19307 (Reactome)
pCofilin Active LIMK-1ArrowREACT_19276 (Reactome)
pLIMK dimer HSP-90REACT_19168 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1907"
Personal tools