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KEGG   PATHWAY: hsa04611
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
Pathway map
hsa04611  Platelet activation
hsa04611

Drug
D00106  Epoprostenol (USAN/INN)
D00109  Aspirin (JP18/USP)
D00769  Clopidogrel bisulfate (USP)
D01028  Ticlopidine hydrochloride (JP18/USP)
D01029  Tirofiban hydrochloride (USAN)
D01188  Pimilprost (JAN/INN)
D01220  Trapidil (JP18/INN)
D01337  Epoprostenol sodium (JAN/USAN)
D01551  Beraprost sodium (JP18/USAN)
D01683  Ozagrel hydrochloride hydrate (JAN)
D01684  Ozagrel sodium (JP18)
D01896  Cilostazol (JP18/USP/INN)
D02048  Clinprost (JAN/INN)
D02720  Beraprost (USAN)
D02721  Iloprost (USAN/INN)
D02778  Abciximab (USAN/INN)
D03359  Cangrelor (USAN/INN)
D03361  Cangrelor tetrasodium (USAN)
D03522  Ciprostene calcium (USAN)
D03642  Daltroban (USAN/INN)
D03661  Dazmegrel (USAN/INN)
D03663  Dazoxiben hydrochloride (USAN)
D03971  Elarofiban (USAN)
D04276  Furegrelate sodium (USAN)
D04500  Ifetroban (USAN/INN)
D04501  Ifetroban sodium (USAN)
D04659  Lamifiban (USAN/INN)
D04785  Lotrafiban hydrochloride (USAN)
D05267  Orbofiban acetate (USAN)
D05502  Pirmagrel (USAN/INN)
D05597  Prasugrel hydrochloride (JAN/USAN)
D05727  Ridogrel (USAN/INN)
D05772  Roxifiban acetate (USAN)
D05834  Sibrafiban (USAN/INN)
D05970  Sulotroban (USAN/INN)
D06077  Terbogrel (USAN/INN)
D06213  Treprostinil (JAN/USAN/INN)
D06280  Vapiprost hydrochloride (JAN/USAN)
D06335  Xemilofiban hydrochloride (USAN)
D06600  Giripladib (USAN)
D06649  Tadocizumab (USAN)
D06888  Eptifibatide (INN)
D07140  Picotamide (BAN)
D07141  Indobufen (INN)
D07577  Cinaciguat (JAN/INN)
D07729  Clopidogrel (USP/INN)
D08065  Iloprost tromethamine
D08327  Ozagrel (INN)
D08594  Ticlopidine (INN)
D08607  Tirofiban (INN)
D08628  Treprostinil monosodium salt
D08983  Regrelor disodium (USAN)
D09017  Ticagrelor (JAN/USAN/INN)
D09348  Fostamatinib disodium (USAN)
D09572  Riociguat (JAN/USAN/INN)
D09607  Elinogrel (USAN/INN)
D09608  Elinogrel potassium (USAN)
D09765  Vorapaxar (USAN/INN)
D09766  Vorapaxar sulfate (JAN/USAN)
D09892  Egaptivon pegol (USAN)
D09994  Selexipag (JAN/USAN/INN)
D10430  Treprostinil diolamine (USAN)
D10758  Turoctocog alfa pegol (genetical recombination) (JAN)
D10823  Clopidogrel hydrochloride
D10824  Clopidogrel besilate
D10893  Acalabrutinib (JAN/USAN/INN)
D11051  Vericiguat (JAN/USAN/INN)
D11070  Tirabrutinib hydrochloride (JAN/USAN)
D11160  Caplacizumab (USAN/INN)
D11209  Entospletinib (USAN/INN)
D11274  Praliciguat (USAN/INN)
D11428  Vecabrutinib (USAN/INN)
D11457  Fenebrutinib (USAN/INN)
D11475  Olinciguat (USAN/INN)
D11478  Branebrutinib (USAN)
D11502  Vecabrutinib succinate (USAN)
D11720  Acalabrutinib maleate (USAN)
D11789  Mivavotinib (USAN/INN)
D11790  Mivavotinib citrate (USAN)
D12050  Pirtobrutinib (JAN/USAN)
D12051  Zalunfiban (USAN)
D12052  Luxeptinib (USAN)
D12160  Orelabrutinib (USAN/INN)
D12163  Zalunfiban acetate (USAN)
D12383  Edralbrutinib (USAN/INN)
D12413  Glenzocimab (USAN/INN)
D12504  Nemtabrutinib (USAN/INN)
D12569  Apadamtase alfa (INN)
D12570  Cinaxadamtase alfa (INN)
D12594  Tirabrutinib (USAN/INN)
D12629  Treprostinil phosphate (USAN)
D12704  Acalabrutinib maleate hydrate (JAN)
D12722  Bexotegrast (USAN/INN)
D12835  Apadamtase alfa and cinaxadamtase alfa
D12858  Zelebrudomide (USAN)
D12863  Rondaptivon pegol
D12979  Sumecigrel (USAN)
Other DBs
GO: 0030168
Organism
Homo sapiens (human) [GN:hsa]
Gene
6915  TBXA2R; thromboxane A2 receptor [KO:K04264]
2147  F2; coagulation factor II, thrombin [KO:K01313] [EC:3.4.21.5]
2149  F2R; coagulation factor II thrombin receptor [KO:K03914]
9002  F2RL3; F2R like thrombin or trypsin receptor 3 [KO:K04236]
10672  GNA13; G protein subunit alpha 13 [KO:K04639]
9138  ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
23365  ARHGEF12; Rho guanine nucleotide exchange factor 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:2.7.11.39]
9475  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.39]
5499  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
5500  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
5501  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
4659  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
103910  MYL12B; myosin light chain 12B [KO:K12757]
10627  MYL12A; myosin light chain 12A [KO:K12757]
5023  P2RX1; purinergic receptor P2X 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 P2Y1 [KO:K04270]
2776  GNAQ; G protein subunit alpha q [KO:K04634]
23236  PLCB1; phospholipase C beta 1 [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 [KO:K05858] [EC:3.1.4.11]
5332  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
5590  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
5584  PRKCI; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
10125  RASGRP1; RAS guanyl releasing protein 1 [KO:K04350]
10235  RASGRP2; RAS guanyl releasing protein 2 [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 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 subunit alpha 2b [KO:K06476]
3690  ITGB3; integrin subunit beta 3 [KO:K06493]
83706  FERMT3; FERM domain containing kindlin 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 P2Y12 [KO:K04298]
2770  GNAI1; G protein subunit alpha i1 [KO:K04630]
2773  GNAI3; G protein subunit alpha i3 [KO:K04630]
2771  GNAI2; G protein subunit alpha i2 [KO:K04630]
107  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
108  ADCY2; adenylate cyclase 2 [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 [KO:K08048] [EC:4.6.1.1]
115  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5739  PTGIR; prostaglandin I2 receptor [KO:K04263]
2778  GNAS; GNAS complex locus [KO:K04632]
5294  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
23533  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
146850  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
7408  VASP; vasodilator stimulated phosphoprotein [KO:K06274]
71  ACTG1; actin gamma 1 [KO:K05692]
60  ACTB; actin beta [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 gamma receptor IIa [KO:K06472]
6850  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
1277  COL1A1; collagen type I alpha 1 chain [KO:K06236]
1278  COL1A2; collagen type I alpha 2 chain [KO:K06236]
1281  COL3A1; collagen type III alpha 1 chain [KO:K19720]
51206  GP6; glycoprotein VI platelet [KO:K06264]
2207  FCER1G; Fc epsilon receptor Ig [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 subunit alpha 2 [KO:K06481]
3688  ITGB1; integrin subunit beta 1 [KO:K05719]
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]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
110117499  P3R3URF-PIK3R3; P3R3URF-PIK3R3 readthrough [KO:K02649]
3937  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
5336  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
695  BTK; Bruton 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 subunit alpha [KO:K06261]
2812  GP1BB; glycoprotein Ib platelet subunit beta [KO:K06262]
2815  GP9; glycoprotein IX platelet [KO:K06263]
11093  ADAMTS13; ADAM metallopeptidase with thrombospondin type 1 motif 13 [KO:K08627] [EC:3.4.24.87]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
4846  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
2977  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
2982  GUCY1A1; guanylate cyclase 1 soluble subunit alpha 1 [KO:K12318] [EC:4.6.1.2]
2983  GUCY1B1; guanylate cyclase 1 soluble subunit beta 1 [KO:K12319] [EC:4.6.1.2]
5592  PRKG1; protein kinase cGMP-dependent 1 [KO:K07376] [EC:2.7.11.12]
5593  PRKG2; protein kinase cGMP-dependent 2 [KO:K19477] [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 [KO:K16342] [EC:3.1.1.4]
8681  JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
100137049  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
8605  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
283748  PLA2G4D; phospholipase A2 group IVD [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 [KO:K00509] [EC:1.14.99.1]
6916  TBXAS1; thromboxane A synthase 1 [KO:K01832] [EC:5.3.99.5]
8773  SNAP23; synaptosome associated protein 23 [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
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
PMID:21071698
  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)
DOI:10.1161/ATVBAHA.110.207522
Reference
PMID:22119499
  Authors
Broos K, De Meyer SF, Feys HB, Vanhoorelbeke K, Deckmyn H
  Title
Blood platelet biochemistry.
  Journal
Thromb Res 129:245-9 (2012)
DOI:10.1016/j.thromres.2011.11.002
Reference
PMID:16149014
  Authors
Jurk K, Kehrel BE
  Title
Platelets: physiology and biochemistry.
  Journal
Semin Thromb Hemost 31:381-92 (2005)
DOI:10.1055/s-2005-916671
Reference
PMID:17158345
  Authors
Offermanns S
  Title
Activation of platelet function through G protein-coupled receptors.
  Journal
Circ Res 99:1293-304 (2006)
DOI:10.1161/01.RES.0000251742.71301.16
Reference
PMID:18174460
  Authors
Varga-Szabo D, Pleines I, Nieswandt B
  Title
Cell adhesion mechanisms in platelets.
  Journal
Arterioscler Thromb Vasc Biol 28:403-12 (2008)
DOI:10.1161/ATVBAHA.107.150474
Reference
PMID:18550847
  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)
DOI:10.1182/blood-2008-02-140970
Reference
PMID:19630797
  Authors
Bergmeier W, Stefanini L
  Title
Novel molecules in calcium signaling in platelets.
  Journal
J Thromb Haemost 7 Suppl 1:187-90 (2009)
DOI:10.1111/j.1538-7836.2009.03379.x
Reference
PMID:18544684
  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)
DOI:10.1182/blood-2008-02-139733
Reference
PMID:23106920
  Authors
Heemskerk JW, Mattheij NJ, Cosemans JM
  Title
Platelet-based coagulation: different populations, different functions.
  Journal
J Thromb Haemost 11:2-16 (2013)
DOI:10.1111/jth.12045
Reference
PMID:19286885
  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)
DOI:10.3324/haematol.2008.003178
Reference
PMID:18363565
  Authors
Banno A, Ginsberg MH
  Title
Integrin activation.
  Journal
Biochem Soc Trans 36:229-34 (2008)
DOI:10.1042/BST0360229
Reference
PMID:20089227
  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)
DOI:10.1016/s1885-5857(10)70010-4
Reference
PMID:22701130
  Authors
Joo SJ
  Title
Mechanisms of Platelet Activation and Integrin alphaIIbeta3.
  Journal
Korean Circ J 42:295-301 (2012)
DOI:10.4070/kcj.2012.42.5.295
Reference
PMID:20002545
  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)
DOI:10.1111/j.1538-7836.2009.03722.x
Reference
PMID:23805129
  Authors
Fitch-Tewfik JL, Flaumenhaft R
  Title
Platelet granule exocytosis: a comparison with chromaffin cells.
  Journal
Front Endocrinol (Lausanne) 4:77 (2013)
DOI:10.3389/fendo.2013.00077
Reference
PMID:18641368
  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)
DOI:10.1182/blood-2008-02-142125
Related
pathway
hsa00590  Arachidonic acid metabolism
hsa04015  Rap1 signaling pathway
hsa04020  Calcium signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04610  Complement and coagulation cascades
hsa05211  Renal cell carcinoma
KO pathway
ko04611   
LinkDB

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