Cell surface interactions at the vascular wall (Homo sapiens)

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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>

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History

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Compare	Revision	Action	Time	User	Comment
	112591	view	15:56, 9 October 2020	ReactomeTeam	Reactome version 73
	101507	view	11:37, 1 November 2018	ReactomeTeam	reactome version 66
	101043	view	21:18, 31 October 2018	ReactomeTeam	reactome version 65
	100574	view	19:51, 31 October 2018	ReactomeTeam	reactome version 64
	100123	view	16:37, 31 October 2018	ReactomeTeam	reactome version 63
	99673	view	15:07, 31 October 2018	ReactomeTeam	reactome version 62 (2nd attempt)
	99268	view	12:45, 31 October 2018	ReactomeTeam	reactome version 62
	94057	view	13:54, 16 August 2017	ReactomeTeam	reactome version 61
	93737	view	13:25, 16 August 2017	ReactomeTeam	reactome version 61
	93686	view	11:31, 9 August 2017	ReactomeTeam	reactome version 61
	87157	view	19:14, 18 July 2016	Mkutmon	Ontology Term : 'hemostasis pathway' added !
	86809	view	09:27, 11 July 2016	ReactomeTeam	reactome version 56
	83824	view	13:10, 13 December 2015	Egonw	Marked heparan sulfate (HS) as a metabolite.
	83200	view	10:21, 18 November 2015	ReactomeTeam	Version54
	81579	view	13:07, 21 August 2015	ReactomeTeam	Version53
	77039	view	08:33, 17 July 2014	ReactomeTeam	Fixed remaining interactions
	76744	view	12:10, 16 July 2014	ReactomeTeam	Fixed remaining interactions
	76069	view	10:13, 11 June 2014	ReactomeTeam	Re-fixing comment source
	75779	view	11:29, 10 June 2014	ReactomeTeam	Reactome 48 Update
	75129	view	14:07, 8 May 2014	Anwesha	Fixing comment source for displaying WikiPathways description
	74859	view	15:22, 2 May 2014	Egonw	Marked a metabolite as a DataNode type="Metabolite"...
	74776	view	08:51, 30 April 2014	ReactomeTeam	Reactome46
	42017	view	21:50, 4 March 2011	MaintBot	Automatic update
	39820	view	05:51, 21 January 2011	MaintBot	New pathway

External references

DataNodes

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Name	Type	Database reference	Comment
11xCbxE-GAS6(39-691) [extracellular region]	Protein	Q14393 (Uniprot-TrEMBL)
11xCbxE-PROS1 [extracellular region]	Protein	P07225 (Uniprot-TrEMBL)
8xCbxE-3D-PROC(43-197) [extracellular region]	Protein	P04070 (Uniprot-TrEMBL)
ADP	Metabolite	CHEBI:16761 (ChEBI)
AMICA1 [plasma membrane]	Protein	Q86YT9 (Uniprot-TrEMBL)
AMICA1	Protein	Q86YT9 (Uniprot-TrEMBL)
ANGPT1 [extracellular region]	Protein	Q15389 (Uniprot-TrEMBL)
ANGPT1	Protein	Q15389 (Uniprot-TrEMBL)
ANGPT2 [extracellular region]	Protein	O15123 (Uniprot-TrEMBL)
ANGPT2	Protein	O15123 (Uniprot-TrEMBL)
ANGPT4 [extracellular region]	Protein	Q9Y264 (Uniprot-TrEMBL)
ANGPT4	Protein	Q9Y264 (Uniprot-TrEMBL)
APOB(28-4563) [extracellular region]	Protein	P04114 (Uniprot-TrEMBL)
ATP1B1 [plasma membrane]	Protein	P05026 (Uniprot-TrEMBL)
ATP1B2 [plasma membrane]	Protein	P14415 (Uniprot-TrEMBL)
ATP1B3 [plasma membrane]	Protein	P54709 (Uniprot-TrEMBL)
ATP	Metabolite	CHEBI:15422 (ChEBI)
BSG [Golgi membrane]	Protein	P35613 (Uniprot-TrEMBL)
BSG [plasma membrane]	Protein	P35613 (Uniprot-TrEMBL)
BSG	Protein	P35613 (Uniprot-TrEMBL)
Basigin bound to CD43	Complex	REACT_18170 (Reactome)
Basigin bound to CyPA	Complex	REACT_12714 (Reactome)
Basigin bound to MCTs	Complex	REACT_15052 (Reactome)
Basigin bound to integrins	Complex	REACT_14081 (Reactome)
Basigin homodimer	Complex	REACT_13277 (Reactome)
Basigin-binding integrins	Complex	REACT_14484 (Reactome)
Basigin:CD98hc complex	Complex	REACT_17413 (Reactome)
Basigin:MMP1	Complex	REACT_17528 (Reactome)
Basigin:Mannose-carrying cell recognition molecules	Complex	REACT_18084 (Reactome)
CAV1 [Golgi membrane]	Protein	Q03135 (Uniprot-TrEMBL)
CAV1	Protein	Q03135 (Uniprot-TrEMBL)
CD177 [plasma membrane]	Protein	Q8N6Q3 (Uniprot-TrEMBL)
CD177	Protein	Q8N6Q3 (Uniprot-TrEMBL)
CD2 [plasma membrane]	Protein	P06729 (Uniprot-TrEMBL)
CD244 [plasma membrane]	Protein	Q9BZW8 (Uniprot-TrEMBL)
CD244	Protein	Q9BZW8 (Uniprot-TrEMBL)
CD2	Protein	P06729 (Uniprot-TrEMBL)
CD47 [plasma membrane]	Protein	Q08722 (Uniprot-TrEMBL)
CD47 bound to its ligand	Complex	REACT_12217 (Reactome)
CD47-binding SIRPs	Protein	REACT_12311 (Reactome)
CD47	Protein	Q08722 (Uniprot-TrEMBL)
CD48 [plasma membrane]	Protein	P09326 (Uniprot-TrEMBL)
CD48 bound to CD244	Complex	REACT_12345 (Reactome)
CD48	Protein	P09326 (Uniprot-TrEMBL)
CD58 bound to CD2	Complex	REACT_12230 (Reactome)
CD58(29-235) [plasma membrane]	Protein	P19256 (Uniprot-TrEMBL)
CD58(29-235)	Protein	P19256 (Uniprot-TrEMBL)
CD84 [plasma membrane]	Protein	Q9UIB8 (Uniprot-TrEMBL)
CD84 dimer	Complex	REACT_12135 (Reactome)
CD84	Protein	Q9UIB8 (Uniprot-TrEMBL)
CD98hc complex	Complex	REACT_18154 (Reactome)
CEACAM heterodimer	Complex	REACT_12134 (Reactome)
CEACAM1 [plasma membrane]	Protein	P13688 (Uniprot-TrEMBL)
CEACAM6 [plasma membrane]	Protein	P40199 (Uniprot-TrEMBL)
CEACAM8 [plasma membrane]	Protein	P31997 (Uniprot-TrEMBL)
CHEST [extracellular region]	Metabolite	CHEBI:17002 (ChEBI)
CHOL [extracellular region]	Metabolite	CHEBI:16113 (ChEBI)
CXADR [plasma membrane]	Protein	P78310 (Uniprot-TrEMBL)
CXADR bound to JAML	Complex	REACT_11619 (Reactome)
CXADR	Protein	P78310 (Uniprot-TrEMBL)
Ca2+ [extracellular region]	Metabolite	CHEBI:29108 (ChEBI)
Ca2+ [plasma membrane]	Metabolite	CHEBI:29108 (ChEBI)
Caveolin-1 bound to Basigin	Complex	REACT_13130 (Reactome)
Collagen type I fibril		REACT_150867 (Reactome)
Complex of Tie2:Ang-1	Complex	REACT_12688 (Reactome)
Complex of Tie2:Ang2	Complex	REACT_12895 (Reactome)
CyP60 complexed with Basigin	Complex	REACT_12835 (Reactome)
DOK2 [cytosol]	Protein	O60496 (Uniprot-TrEMBL)
DOK2	Protein	O60496 (Uniprot-TrEMBL)
ESAM [plasma membrane]	Protein	Q96AP7 (Uniprot-TrEMBL)
F11R [plasma membrane]	Protein	Q9Y624 (Uniprot-TrEMBL)
F11R	Protein	Q9Y624 (Uniprot-TrEMBL)
FCER1G [plasma membrane]	Protein	P30273 (Uniprot-TrEMBL)
FN1 dimer	Complex	REACT_14040 (Reactome)
FN1(32-2386) [extracellular region]	Protein	P02751 (Uniprot-TrEMBL)
FYN(2-537) [cytosol]	Protein	P06241 (Uniprot-TrEMBL)
GDP [cytosol]	Metabolite	CHEBI:17552 (ChEBI)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GP6 [plasma membrane]	Protein	Q9HCN6 (Uniprot-TrEMBL)
GPVI:FceRI gamma:FYN:LYN:Collagen type I	Complex	REACT_20373 (Reactome)
GPVI:FceRI gamma:FYN:LYN	Complex	REACT_20322 (Reactome)
GRB14 [cytosol]	Protein	Q14449 (Uniprot-TrEMBL)
GRB14	Protein	Q14449 (Uniprot-TrEMBL)
GRB2-1 [cytosol]	Protein	P62993-1 (Uniprot-TrEMBL)
GRB2-1	Protein	P62993-1 (Uniprot-TrEMBL)
GRB7 [cytosol]	Protein	Q14451 (Uniprot-TrEMBL)
GRB7	Protein	Q14451 (Uniprot-TrEMBL)
GTP [cytosol]	Metabolite	CHEBI:15996 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
Grb2 bound to Tie2	Complex	REACT_12659 (Reactome)
HRAS(1-186) [plasma membrane]	Protein	P01112 (Uniprot-TrEMBL)
Heparan Sulphate		CHEBI:28815 (ChEBI)
INPP5D [cytosol]	Protein	Q92835 (Uniprot-TrEMBL)
INPP5D	Protein	Q92835 (Uniprot-TrEMBL)
ITGA3(33-1051) [plasma membrane]	Protein	P26006 (Uniprot-TrEMBL)
ITGA4(40-1038) [plasma membrane]	Protein	P13612 (Uniprot-TrEMBL)
ITGA5(42-894) [plasma membrane]	Protein	P08648 (Uniprot-TrEMBL)
ITGA6(24-1130) [plasma membrane]	Protein	P23229 (Uniprot-TrEMBL)
ITGAL [plasma membrane]	Protein	P20701 (Uniprot-TrEMBL)
ITGAM [plasma membrane]	Protein	P11215 (Uniprot-TrEMBL)
ITGAV(31-1048) [plasma membrane]	Protein	P06756 (Uniprot-TrEMBL)
ITGAX [plasma membrane]	Protein	P20702 (Uniprot-TrEMBL)
ITGB1 [plasma membrane]	Protein	P05556 (Uniprot-TrEMBL)
ITGB2 [plasma membrane]	Protein	P05107 (Uniprot-TrEMBL)
ITGB3 [plasma membrane]	Protein	P05106 (Uniprot-TrEMBL)
Integrin alpha5beta1:Fibronectin	Complex	REACT_12353 (Reactome)
Integrin alphaMbeta2:JAM3	Complex	REACT_12228 (Reactome)
Integrin alphaVbeta3:PECAM-1	Complex	REACT_13361 (Reactome)
Integrin alphaXbeta2:AMICA1	Complex	REACT_12224 (Reactome)
Integrin alpha5beta1	Complex	REACT_12335 (Reactome)
Integrin alphaLbeta2 (LFA-1)	Complex	REACT_11837 (Reactome)
Integrin alphaMbeta2	Complex	REACT_12291 (Reactome)
Integrin alphaVbeta3	Complex	REACT_13287 (Reactome)
Integrin alphaXbeta2	Complex	REACT_12091 (Reactome)
JAM-A Homodimer	Complex	REACT_12319 (Reactome)
JAM-B bound to JAM-C	Complex	REACT_12255 (Reactome)
JAM-B homodimer	Complex	REACT_12209 (Reactome)
JAM-C homodimer	Complex	REACT_12100 (Reactome)
JAM2 [plasma membrane]	Protein	P57087 (Uniprot-TrEMBL)
JAM2(20-394) [plasma membrane]	Protein	P57087 (Uniprot-TrEMBL)
JAM2	Protein	P57087 (Uniprot-TrEMBL)
JAM3 [plasma membrane]	Protein	Q9BX67 (Uniprot-TrEMBL)
JAM3	Protein	Q9BX67 (Uniprot-TrEMBL)
KRAS(1-186) [plasma membrane]	Protein	P01116 (Uniprot-TrEMBL)
L1CAM [plasma membrane]	Protein	P32004 (Uniprot-TrEMBL)
LDL	Complex	REACT_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-A	Complex	REACT_12182 (Reactome)
LYN(2-512) [cytosol]	Protein	P07948 (Uniprot-TrEMBL)
Ligand to TREM-1 on the platelet membrane		REACT_12176 (Reactome)
MAG [plasma membrane]	Protein	P20916 (Uniprot-TrEMBL)
MERTK [plasma membrane]	Protein	Q12866 (Uniprot-TrEMBL)
MERTK bound to its ligand	Complex	REACT_12164 (Reactome)
MERTK ligands	Protein	REACT_12235 (Reactome)
MERTK	Protein	Q12866 (Uniprot-TrEMBL)
MMP1(100-469) [extracellular region]	Protein	P03956 (Uniprot-TrEMBL)
MMP1(100-469)	Protein	P03956 (Uniprot-TrEMBL)
Mannose-carrying cell recognition molecules	Complex	REACT_18192 (Reactome)
Mn2+ [extracellular region]	Metabolite	CHEBI:18291 (ChEBI)
Mn2+	Metabolite	CHEBI:18291 (ChEBI)
Monocarboxylate Transporter Set (MCT)	Protein	REACT_17955 (Reactome)
NRAS [plasma membrane]	Protein	P01111 (Uniprot-TrEMBL)
Neutrophil CEACAMs affecting integrin binding to fibronectin	Protein	REACT_12292 (Reactome)
OLR1 [plasma membrane]	Protein	P78380 (Uniprot-TrEMBL)
OLR1 bound to oxidized LDL	Complex	REACT_12181 (Reactome)
OLR1	Protein	P78380 (Uniprot-TrEMBL)
P-selectin bound to its ligand	Complex	REACT_12193 (Reactome)
PECAM-1 bound to CD177	Complex	REACT_12173 (Reactome)
PECAM-1:PECAM-1	Complex	REACT_13059 (Reactome)
PECAM-1:PLC gamma1 complex	Complex	REACT_13045 (Reactome)
PECAM-1:SHIP1 complex	Complex	REACT_13027 (Reactome)
PECAM-1:SHP-1 complex	Complex	REACT_13228 (Reactome)
PECAM-1:SHP-2 complex	Complex	REACT_13041 (Reactome)
PECAM1(27-?) [plasma membrane]	Protein	P16284 (Uniprot-TrEMBL)
PECAM1(27-?)	Protein	P16284 (Uniprot-TrEMBL)
PI3K	Complex	REACT_4240 (Reactome)
PIK3CA [cytosol]	Protein	P42336 (Uniprot-TrEMBL)
PIK3CB [cytosol]	Protein	P42338 (Uniprot-TrEMBL)
PIK3R1 [cytosol]	Protein	P27986 (Uniprot-TrEMBL)
PIK3R2 [cytosol]	Protein	O00459 (Uniprot-TrEMBL)
PL [extracellular region]	Metabolite	CHEBI:16247 (ChEBI)
PLCG1(2-1290) [cytosol]	Protein	P19174 (Uniprot-TrEMBL)
PLCG1(2-1290)	Protein	P19174 (Uniprot-TrEMBL)
PPIA [extracellular region]	Protein	P62937 (Uniprot-TrEMBL)
PPIA	Protein	P62937 (Uniprot-TrEMBL)
PPIL2 [Golgi lumen]	Protein	Q13356 (Uniprot-TrEMBL)
PPIL2	Protein	Q13356 (Uniprot-TrEMBL)
PROC(200-211)	Protein	P04070 (Uniprot-TrEMBL)
PROC(200-461) [extracellular region]	Protein	P04070 (Uniprot-TrEMBL)
PROC(212-461) [extracellular region]	Protein	P04070 (Uniprot-TrEMBL)
PTPN11 [cytosol]	Protein	Q06124 (Uniprot-TrEMBL)
PTPN11	Protein	Q06124 (Uniprot-TrEMBL)
PTPN6 [cytosol]	Protein	P29350 (Uniprot-TrEMBL)
PTPN6	Protein	P29350 (Uniprot-TrEMBL)
Phosphorylated Tie2 in Tie2/Akt dimer	Complex	REACT_13046 (Reactome)
Platelet Factor 4		REACT_12205 (Reactome)
SELE [plasma membrane]	Protein	P16581 (Uniprot-TrEMBL)
SELL [plasma membrane]	Protein	P14151 (Uniprot-TrEMBL)
SELP [plasma membrane]	Protein	P16109 (Uniprot-TrEMBL)
SELPLG [plasma membrane]	Protein	Q14242 (Uniprot-TrEMBL)
SELPLG	Protein	Q14242 (Uniprot-TrEMBL)
SHC1 [cytosol]	Protein	P29353 (Uniprot-TrEMBL)
SHC1	Protein	P29353 (Uniprot-TrEMBL)
SIRPA [plasma membrane]	Protein	P78324 (Uniprot-TrEMBL)
SIRPG [plasma membrane]	Protein	Q9P1W8 (Uniprot-TrEMBL)
SLC16A1 [plasma membrane]	Protein	P53985 (Uniprot-TrEMBL)
SLC16A3(1-465) [plasma membrane]	Protein	O15427 (Uniprot-TrEMBL)
SLC16A8 [plasma membrane]	Protein	O95907 (Uniprot-TrEMBL)
SLC3A2 [plasma membrane]	Protein	P08195 (Uniprot-TrEMBL)
SLC7A10 [plasma membrane]	Protein	Q9NS82 (Uniprot-TrEMBL)
SLC7A11 [plasma membrane]	Protein	Q9UPY5 (Uniprot-TrEMBL)
SLC7A5 [plasma membrane]	Protein	Q01650 (Uniprot-TrEMBL)
SLC7A6 [plasma membrane]	Protein	Q92536 (Uniprot-TrEMBL)
SLC7A7 [plasma membrane]	Protein	Q9UM01 (Uniprot-TrEMBL)
SLC7A8 [plasma membrane]	Protein	Q9UHI5 (Uniprot-TrEMBL)
SLC7A9 [plasma membrane]	Protein	P82251 (Uniprot-TrEMBL)
SOS-1 bound to Tie2:Grb2	Complex	REACT_13320 (Reactome)
SOS1 [cytosol]	Protein	Q07889 (Uniprot-TrEMBL)
SOS1	Protein	Q07889 (Uniprot-TrEMBL)
SPN [plasma membrane]	Protein	P16150 (Uniprot-TrEMBL)
SPN	Protein	P16150 (Uniprot-TrEMBL)
Selectin	Protein	REACT_12297 (Reactome)
Src family tyrosine kinases (SFKs)		REACT_13328 (Reactome)
TAGs [extracellular region]	Metabolite	CHEBI:17855 (ChEBI)
TEK [plasma membrane]	Protein	Q02763 (Uniprot-TrEMBL)
TEK	Protein	Q02763 (Uniprot-TrEMBL)
THBD(22-575) [plasma membrane]	Protein	P07204 (Uniprot-TrEMBL)
TREM-1 bound to its ligand	Complex	REACT_12367 (Reactome)
TREM1 [plasma membrane]	Protein	Q9NP99 (Uniprot-TrEMBL)
TREM1	Protein	Q9NP99 (Uniprot-TrEMBL)
Tie2 and Ang4 complex	Complex	REACT_12703 (Reactome)
Tie2 and Dok-2 complex	Complex	REACT_13019 (Reactome)
Tie2 and Grb14 complex	Complex	REACT_18185 (Reactome)
Tie2/Ang1 dimer	Complex	REACT_13336 (Reactome)
Tie2:Grb7 complex	Complex	REACT_18058 (Reactome)
VLA-4: JAM-B	Complex	REACT_12179 (Reactome)
VLA-4	Complex	REACT_11798 (Reactome)
activated thrombin:thrombomodulin	Complex	REACT_5904 (Reactome)
activated protein C	Complex	REACT_2599 (Reactome)
p-5Y,S1119-TEK [plasma membrane]	Protein	Q02763 (Uniprot-TrEMBL)
p-PECAM1:p-PECAM1	Complex	REACT_12801 (Reactome)
p-Y663,Y686-PECAM1(27-?) [plasma membrane]	Protein	P16284 (Uniprot-TrEMBL)
p-Y663,Y686-PECAM1(27-?)	Protein	P16284 (Uniprot-TrEMBL)
p21 RAS:GDP	Complex	REACT_2657 (Reactome)
p21 RAS:GTP	Complex	REACT_4782 (Reactome)
p85 bound to Tie2	Complex	REACT_13298 (Reactome)
pTie2 and SHP2 complex	Complex	REACT_17975 (Reactome)
pTie2:Ang-1	Complex	REACT_13342 (Reactome)
pTie2:SHC1 complex	Complex	REACT_12988 (Reactome)
protein C	Complex	REACT_4912 (Reactome)
thrombin heavy chain [plasma membrane]	Protein	P00734 (Uniprot-TrEMBL)
thrombin light chain [plasma membrane]	Protein	P00734 (Uniprot-TrEMBL)

Annotated Interactions

View all...

Source	Target	Type	Database reference	Comment
	ADP	Arrow	REACT_12408 (Reactome)
	ADP	Arrow	REACT_12496 (Reactome)
AMICA1			REACT_11154 (Reactome)
AMICA1			REACT_12064 (Reactome)
ANGPT1			REACT_12523 (Reactome)
ANGPT2			REACT_12547 (Reactome)
ANGPT4			REACT_12598 (Reactome)
ATP			REACT_12408 (Reactome)
ATP			REACT_12496 (Reactome)
BSG			REACT_12497 (Reactome)
BSG			REACT_12550 (Reactome)
BSG			REACT_12593 (Reactome)
BSG			REACT_12637 (Reactome)
BSG			REACT_13430 (Reactome)
BSG			REACT_16882 (Reactome)
BSG			REACT_16931 (Reactome)
BSG			REACT_16941 (Reactome)
BSG			REACT_16975 (Reactome)
BSG			REACT_16988 (Reactome)
	Basigin bound to CD43	Arrow	REACT_16931 (Reactome)
	Basigin bound to CyPA	Arrow	REACT_12497 (Reactome)
	Basigin bound to MCTs	Arrow	REACT_16882 (Reactome)
	Basigin bound to integrins	Arrow	REACT_13430 (Reactome)
	Basigin homodimer	Arrow	REACT_12593 (Reactome)
Basigin-binding integrins			REACT_13430 (Reactome)
	Basigin:CD98hc complex	Arrow	REACT_16988 (Reactome)
	Basigin:MMP1	Arrow	REACT_16941 (Reactome)
	Basigin:Mannose-carrying cell recognition molecules	Arrow	REACT_16975 (Reactome)
CAV1			REACT_12637 (Reactome)
CD177			REACT_12006 (Reactome)
CD244			REACT_12018 (Reactome)
CD2			REACT_12031 (Reactome)
	CD47 bound to its ligand	Arrow	REACT_12068 (Reactome)
CD47-binding SIRPs			REACT_12068 (Reactome)
CD47			REACT_12068 (Reactome)
	CD48 bound to CD244	Arrow	REACT_12018 (Reactome)
CD48			REACT_12018 (Reactome)
	CD58 bound to CD2	Arrow	REACT_12031 (Reactome)
CD58(29-235)			REACT_12031 (Reactome)
	CD84 dimer	Arrow	REACT_12027 (Reactome)
CD84			REACT_12027 (Reactome)
CD98hc complex			REACT_16988 (Reactome)
	CEACAM heterodimer	Arrow	REACT_12073 (Reactome)
	CXADR bound to JAML	Arrow	REACT_11154 (Reactome)
CXADR			REACT_11154 (Reactome)
	Caveolin-1 bound to Basigin	Arrow	REACT_12637 (Reactome)
Collagen type I fibril			REACT_1088 (Reactome)
	Complex of Tie2:Ang-1	Arrow	REACT_12523 (Reactome)
Complex of Tie2:Ang-1			REACT_12431 (Reactome)
Complex of Tie2:Ang-1		mim-catalysis	REACT_12496 (Reactome)
	Complex of Tie2:Ang2	Arrow	REACT_12547 (Reactome)
	CyP60 complexed with Basigin	Arrow	REACT_12550 (Reactome)
DOK2			REACT_12575 (Reactome)
F11R			REACT_11999 (Reactome)
F11R			REACT_12042 (Reactome)
FN1 dimer			REACT_12043 (Reactome)
	GDP	Arrow	REACT_12516 (Reactome)
	GPVI:FceRI gamma:FYN:LYN:Collagen type I	Arrow	REACT_1088 (Reactome)
GPVI:FceRI gamma:FYN:LYN			REACT_1088 (Reactome)
GRB14			REACT_16885 (Reactome)
GRB2-1			REACT_12511 (Reactome)
GRB7			REACT_16914 (Reactome)
GTP			REACT_12516 (Reactome)
	Grb2 bound to Tie2	Arrow	REACT_12511 (Reactome)
Grb2 bound to Tie2			REACT_12504 (Reactome)
Heparan Sulphate		Arrow	REACT_12497 (Reactome)
INPP5D			REACT_12476 (Reactome)
	Integrin alpha5beta1:Fibronectin	Arrow	REACT_12043 (Reactome)
	Integrin alphaMbeta2:JAM3	Arrow	REACT_12035 (Reactome)
	Integrin alphaVbeta3:PECAM-1	Arrow	REACT_12468 (Reactome)
	Integrin alphaXbeta2:AMICA1	Arrow	REACT_12064 (Reactome)
Integrin alpha5beta1			REACT_12043 (Reactome)
Integrin alphaLbeta2 (LFA-1)			REACT_12042 (Reactome)
Integrin alphaMbeta2			REACT_12035 (Reactome)
Integrin alphaVbeta3			REACT_12468 (Reactome)
Integrin alphaXbeta2			REACT_12064 (Reactome)
	JAM-A Homodimer	Arrow	REACT_11999 (Reactome)
	JAM-B bound to JAM-C	Arrow	REACT_12053 (Reactome)
	JAM-B homodimer	Arrow	REACT_11994 (Reactome)
	JAM-C homodimer	Arrow	REACT_12029 (Reactome)
JAM2			REACT_11994 (Reactome)
JAM2			REACT_12040 (Reactome)
JAM2			REACT_12053 (Reactome)
JAM3			REACT_12029 (Reactome)
JAM3			REACT_12035 (Reactome)
JAM3			REACT_12053 (Reactome)
LDL			REACT_12039 (Reactome)
	LFA-1:JAM-A	Arrow	REACT_12042 (Reactome)
Ligand to TREM-1 on the platelet membrane			REACT_12047 (Reactome)
	MERTK bound to its ligand	Arrow	REACT_12060 (Reactome)
MERTK ligands			REACT_12060 (Reactome)
MERTK			REACT_12060 (Reactome)
MMP1(100-469)			REACT_16941 (Reactome)
Mannose-carrying cell recognition molecules			REACT_16975 (Reactome)
Mn2+			REACT_12043 (Reactome)
Monocarboxylate Transporter Set (MCT)			REACT_16882 (Reactome)
Neutrophil CEACAMs affecting integrin binding to fibronectin			REACT_12073 (Reactome)
	OLR1 bound to oxidized LDL	Arrow	REACT_12039 (Reactome)
OLR1			REACT_12039 (Reactome)
	P-selectin bound to its ligand	Arrow	REACT_12081 (Reactome)
	PECAM-1 bound to CD177	Arrow	REACT_12006 (Reactome)
	PECAM-1:PECAM-1	Arrow	REACT_12419 (Reactome)
PECAM-1:PECAM-1			REACT_12408 (Reactome)
	PECAM-1:PLC gamma1 complex	Arrow	REACT_12540 (Reactome)
	PECAM-1:SHIP1 complex	Arrow	REACT_12476 (Reactome)
	PECAM-1:SHP-1 complex	Arrow	REACT_12552 (Reactome)
	PECAM-1:SHP-2 complex	Arrow	REACT_12509 (Reactome)
PECAM1(27-?)			REACT_12006 (Reactome)
PECAM1(27-?)			REACT_12419 (Reactome)
PECAM1(27-?)			REACT_12468 (Reactome)
PI3K			REACT_12475 (Reactome)
PLCG1(2-1290)			REACT_12540 (Reactome)
PPIA			REACT_12497 (Reactome)
PPIL2			REACT_12550 (Reactome)
	PROC(200-211)	Arrow	REACT_374 (Reactome)
PTPN11			REACT_12509 (Reactome)
PTPN11			REACT_16906 (Reactome)
PTPN6			REACT_12552 (Reactome)
	Phosphorylated Tie2 in Tie2/Akt dimer	Arrow	REACT_12496 (Reactome)
Platelet Factor 4		Arrow	REACT_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.
SELPLG			REACT_12081 (Reactome)
SHC1			REACT_12409 (Reactome)
	SOS-1 bound to Tie2:Grb2	Arrow	REACT_12504 (Reactome)
SOS-1 bound to Tie2:Grb2		mim-catalysis	REACT_12516 (Reactome)
SOS1			REACT_12504 (Reactome)
SPN			REACT_16931 (Reactome)
Selectin			REACT_12081 (Reactome)
Src family tyrosine kinases (SFKs)		mim-catalysis	REACT_12408 (Reactome)
TEK			REACT_12523 (Reactome)
TEK			REACT_12547 (Reactome)
TEK			REACT_12598 (Reactome)
	TREM-1 bound to its ligand	Arrow	REACT_12047 (Reactome)
TREM1			REACT_12047 (Reactome)
	Tie2 and Ang4 complex	Arrow	REACT_12598 (Reactome)
	Tie2 and Dok-2 complex	Arrow	REACT_12575 (Reactome)
	Tie2 and Grb14 complex	Arrow	REACT_16885 (Reactome)
	Tie2/Ang1 dimer	Arrow	REACT_12431 (Reactome)
Tie2/Ang1 dimer			REACT_12496 (Reactome)
	Tie2:Grb7 complex	Arrow	REACT_16914 (Reactome)
	VLA-4: JAM-B	Arrow	REACT_12040 (Reactome)
VLA-4			REACT_12040 (Reactome)
activated thrombin:thrombomodulin		mim-catalysis	REACT_374 (Reactome)
	activated protein C	Arrow	REACT_374 (Reactome)
	p-PECAM1:p-PECAM1	Arrow	REACT_12408 (Reactome)
p-Y663,Y686-PECAM1(27-?)			REACT_12476 (Reactome)
p-Y663,Y686-PECAM1(27-?)			REACT_12509 (Reactome)
p-Y663,Y686-PECAM1(27-?)			REACT_12540 (Reactome)
p-Y663,Y686-PECAM1(27-?)			REACT_12552 (Reactome)
p21 RAS:GDP			REACT_12516 (Reactome)
	p21 RAS:GTP	Arrow	REACT_12516 (Reactome)
	p85 bound to Tie2	Arrow	REACT_12475 (Reactome)
	pTie2 and SHP2 complex	Arrow	REACT_16906 (Reactome)
pTie2:Ang-1			REACT_12409 (Reactome)
pTie2:Ang-1			REACT_12475 (Reactome)
pTie2:Ang-1			REACT_12511 (Reactome)
pTie2:Ang-1			REACT_12575 (Reactome)
pTie2:Ang-1			REACT_16885 (Reactome)
pTie2:Ang-1			REACT_16906 (Reactome)
pTie2:Ang-1			REACT_16914 (Reactome)
	pTie2:SHC1 complex	Arrow	REACT_12409 (Reactome)
protein C			REACT_374 (Reactome)