KEGG   PATHWAY: hsa04611Help
Entry
hsa04611                    Pathway                                

Name
Platelet activation - Homo sapiens (human)
Description
Platelets play a key and beneficial role for primary hemostasis on the disruption of the integrity of vessel wall. Platelet adhesion and activation at sites of vascular wall injury is initiated by adhesion to adhesive macromolecules, such as collagen and von Willebrand factor (vWF), or by soluble platelet agonists, such as ADP, thrombin, and thromboxane A2. Different receptors are stimulated by various agonists, almost converging in increasing intracellular Ca2+ concentration that stimulate platelet shape change and granule secretion and ultimately induce the "inside-out" signaling process leading to activation of the ligand-binding function of integrin alpha IIb beta 3. Binding of alpha IIb beta 3 to its ligands, mainly fibrinogen, mediates platelet adhesion and aggregation and triggers "outside-in" signaling, resulting in platelet spreading, additional granule secretion, stabilization of platelet adhesion and aggregation, and clot retraction.
Class
Organismal Systems; Immune system
BRITE hierarchy
Pathway map
Platelet activation
hsa04611

All organismsOrtholog table
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
6915  
TBXA2R; thromboxane A2 receptor [KO:K04264]
2149  
F2R; coagulation factor II (thrombin) receptor [KO:K03914]
9002  
F2RL3; coagulation factor II (thrombin) receptor-like 3 [KO:K04236]
10672  
GNA13; guanine nucleotide binding protein (G protein), alpha 13 [KO:K04639]
9138  
ARHGEF1; Rho guanine nucleotide exchange factor (GEF) 1 [KO:K12330]
23365  
ARHGEF12; Rho guanine nucleotide exchange factor (GEF) 12 [KO:K07532]
387  
RHOA; ras homolog family member A [KO:K04513]
6093  
ROCK1; Rho-associated, coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
9475  
ROCK2; Rho-associated, coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
5499  
PPP1CA; protein phosphatase 1, catalytic subunit, alpha isozyme [KO:K06269] [EC:3.1.3.16]
5500  
PPP1CB; protein phosphatase 1, catalytic subunit, beta isozyme [KO:K06269] [EC:3.1.3.16]
5501  
PPP1CC; protein phosphatase 1, catalytic subunit, gamma isozyme [KO:K06269] [EC:3.1.3.16]
4659  
PPP1R12A; protein phosphatase 1, regulatory subunit 12A [KO:K06270]
103910  
MYL12B; myosin, light chain 12B, regulatory [KO:K12757]
10627  
MYL12A; myosin, light chain 12A, regulatory, non-sarcomeric [KO:K12757]
5023  
P2RX1; purinergic receptor P2X, ligand-gated ion channel, 1 [KO:K05215]
84876  
ORAI1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
6786  
STIM1; stromal interaction molecule 1 [KO:K16059]
4638  
MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
85366  
MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
91807  
MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
340156  
MYLK4; myosin light chain kinase family, member 4 [KO:K00907] [EC:2.7.11.18]
5028  
P2RY1; purinergic receptor P2Y, G-protein coupled, 1 [KO:K04270]
2776  
GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
5584  
PRKCI; protein kinase C, iota [KO:K06069] [EC:2.7.11.13]
5590  
PRKCZ; protein kinase C, zeta [KO:K06069] [EC:2.7.11.13]
10125  
RASGRP1; RAS guanyl releasing protein 1 (calcium and DAG-regulated) [KO:K04350]
10235  
RASGRP2; RAS guanyl releasing protein 2 (calcium and DAG-regulated) [KO:K12361]
5906  
RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
5908  
RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
54518  
APBB1IP; amyloid beta (A4) precursor protein-binding, family B, member 1 interacting protein [KO:K17704]
7094  
TLN1; talin 1 [KO:K06271]
83660  
TLN2; talin 2 [KO:K06271]
3674  
ITGA2B; integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41) [KO:K06476]
3690  
ITGB3; integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) [KO:K06493]
83706  
FERMT3; fermitin family member 3 [KO:K17084]
2243  
FGA; fibrinogen alpha chain [KO:K03903]
2244  
FGB; fibrinogen beta chain [KO:K03904]
2266  
FGG; fibrinogen gamma chain [KO:K03905]
64805  
P2RY12; purinergic receptor P2Y, G-protein coupled, 12 [KO:K04298]
2770  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5739  
PTGIR; prostaglandin I2 (prostacyclin) receptor (IP) [KO:K04263]
2778  
GNAS; GNAS complex locus [KO:K04632]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
7408  
VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
60  
ACTB; actin, beta [KO:K05692]
71  
ACTG1; actin, gamma 1 [KO:K05692]
6714  
SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
2909  
ARHGAP35; Rho GTPase activating protein 35 [KO:K05732]
2212  
FCGR2A; Fc fragment of IgG, low affinity IIa, receptor (CD32) [KO:K06472]
6850  
SYK; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
1277  
COL1A1; collagen, type I, alpha 1 [KO:K06236]
1278  
COL1A2; collagen, type I, alpha 2 [KO:K06236]
1280  
COL2A1; collagen, type II, alpha 1 [KO:K06236]
1281  
COL3A1; collagen, type III, alpha 1 [KO:K06236]
1289  
COL5A1; collagen, type V, alpha 1 [KO:K06236]
1290  
COL5A2; collagen, type V, alpha 2 [KO:K06236]
1301  
COL11A1; collagen, type XI, alpha 1 [KO:K06236]
1302  
COL11A2; collagen, type XI, alpha 2 [KO:K06236]
50509  
COL5A3; collagen, type V, alpha 3 [KO:K06236]
255631  
COL24A1; collagen, type XXIV, alpha 1 [KO:K06236]
85301  
COL27A1; collagen, type XXVII, alpha 1 [KO:K06236]
51206  
GP6; glycoprotein VI (platelet) [KO:K06264]
2207  
FCER1G; Fc fragment of IgE, high affinity I, receptor for [KO:K07983]
4067  
LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
2534  
FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
3673  
ITGA2; integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) [KO:K06481]
3688  
ITGB1; integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) [KO:K05719]
3937  
LCP2; lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) [KO:K07361]
5336  
PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
695  
BTK; Bruton agammaglobulinemia tyrosine kinase [KO:K07370] [EC:2.7.10.2]
7450  
VWF; von Willebrand factor [KO:K03900]
2814  
GP5; glycoprotein V (platelet) [KO:K06260]
2811  
GP1BA; glycoprotein Ib (platelet), alpha polypeptide [KO:K06261]
2812  
GP1BB; glycoprotein Ib (platelet), beta polypeptide [KO:K06262]
2815  
GP9; glycoprotein IX (platelet) [KO:K06263]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
4846  
NOS3; nitric oxide synthase 3 (endothelial cell) [KO:K13242] [EC:1.14.13.39]
2977  
GUCY1A2; guanylate cyclase 1, soluble, alpha 2 [KO:K12318] [EC:4.6.1.2]
2982  
GUCY1A3; guanylate cyclase 1, soluble, alpha 3 [KO:K12318] [EC:4.6.1.2]
2983  
GUCY1B3; guanylate cyclase 1, soluble, beta 3 [KO:K12319] [EC:4.6.1.2]
5592  
PRKG1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
5593  
PRKG2; protein kinase, cGMP-dependent, type II [KO:K07376] [EC:2.7.11.12]
5600  
MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  
MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  
MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123745  
PLA2G4E; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
5321  
PLA2G4A; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
8681  
JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
PLA2G4B; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
8605  
PLA2G4C; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
283748  
PLA2G4D; phospholipase A2, group IVD (cytosolic) [KO:K16342] [EC:3.1.1.4]
255189  
PLA2G4F; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
5742  
PTGS1; prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) [KO:K00509] [EC:1.14.99.1]
6916  
TBXAS1; thromboxane A synthase 1 (platelet) [KO:K01832] [EC:5.3.99.5]
8773  
SNAP23; synaptosomal-associated protein, 23kDa [KO:K08508]
8673  
VAMP8; vesicle-associated membrane protein 8 [KO:K08512]
Compound
C00002  
ATP
C00008  
ADP
C00076  
Calcium cation
C00165  
Diacylglycerol
C00219  
Arachidonate
C00427  
Prostaglandin H2
C00533  
Nitric oxide
C00575  
3',5'-Cyclic AMP
C00752  
Thrombin
C00942  
3',5'-Cyclic GMP
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C01312  
Prostaglandin I2
C02198  
Thromboxane A2
C05956  
Prostaglandin G2
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Li Z, Delaney MK, O'Brien KA, Du X
  Title
Signaling during platelet adhesion and activation.
  Journal
Arterioscler Thromb Vasc Biol 30:2341-9 (2010)
Reference
  Authors
Broos K, De Meyer SF, Feys HB, Vanhoorelbeke K, Deckmyn H
  Title
Blood platelet biochemistry.
  Journal
Thromb Res 129:245-9 (2012)
Reference
  Authors
Jurk K, Kehrel BE
  Title
Platelets: physiology and biochemistry.
  Journal
Semin Thromb Hemost 31:381-92 (2005)
Reference
  Authors
Offermanns S
  Title
Activation of platelet function through G protein-coupled receptors.
  Journal
Circ Res 99:1293-304 (2006)
Reference
  Authors
Varga-Szabo D, Pleines I, Nieswandt B
  Title
Cell adhesion mechanisms in platelets.
  Journal
Arterioscler Thromb Vasc Biol 28:403-12 (2008)
Reference
  Authors
Yin H, Liu J, Li Z, Berndt MC, Lowell CA, Du X
  Title
Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway.
  Journal
Blood 112:1139-46 (2008)
Reference
  Authors
Bergmeier W, Stefanini L
  Title
Novel molecules in calcium signaling in platelets.
  Journal
J Thromb Haemost 7 Suppl 1:187-90 (2009)
Reference
  Authors
Cifuni SM, Wagner DD, Bergmeier W
  Title
CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets.
  Journal
Blood 112:1696-703 (2008)
Reference
  Authors
Heemskerk JW, Mattheij NJ, Cosemans JM
  Title
Platelet-based coagulation: different populations, different functions.
  Journal
J Thromb Haemost 11:2-16 (2013)
Reference
  Authors
Rivera J, Lozano ML, Navarro-Nunez L, Vicente V
  Title
Platelet receptors and signaling in the dynamics of thrombus formation.
  Journal
Haematologica 94:700-11 (2009)
Reference
  Authors
Banno A, Ginsberg MH
  Title
Integrin activation.
  Journal
Biochem Soc Trans 36:229-34 (2008)
Reference
  Authors
Angiolillo DJ, Ferreiro JL
  Title
Platelet adenosine diphosphate P2Y12 receptor antagonism: benefits and limitations of current treatment strategies and future directions.
  Journal
Rev Esp Cardiol 63:60-76 (2010)
Reference
  Authors
Joo SJ
  Title
Mechanisms of Platelet Activation and Integrin alphaIIbeta3.
  Journal
Korean Circ J 42:295-301 (2012)
Reference
  Authors
Harper MT, Poole AW
  Title
Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation.
  Journal
J Thromb Haemost 8:454-62 (2010)
Reference
  Authors
Fitch-Tewfik JL, Flaumenhaft R
  Title
Platelet granule exocytosis: a comparison with chromaffin cells.
  Journal
Front Endocrinol (Lausanne) 4:77 (2013)
Reference
  Authors
Boylan B, Gao C, Rathore V, Gill JC, Newman DK, Newman PJ
  Title
Identification of FcgammaRIIa as the ITAM-bearing receptor mediating alphaIIbbeta3 outside-in integrin signaling in human platelets.
  Journal
Blood 112:2780-6 (2008)
KO pathway
 

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