Platelet activation - Homo sapiens (human)
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.
Organismal Systems; Immune system
Pathway map Ortholog table
D00106 Epoprostenol (USAN/INN)
D00769 Clopidogrel bisulfate (USP)
D01028 Ticlopidine hydrochloride (JP18/USP)
D01029 Tirofiban hydrochloride (USAN)
D01337 Epoprostenol sodium (JAN/USAN)
D01551 Beraprost sodium (JP18/USAN)
D01683 Ozagrel hydrochloride hydrate (JAN)
D01896 Cilostazol (JP18/USP/INN)
D03361 Cangrelor tetrasodium (USAN)
D03522 Ciprostene calcium (USAN)
D03663 Dazoxiben hydrochloride (USAN)
D04276 Furegrelate sodium (USAN)
D04501 Ifetroban sodium (USAN)
D04785 Lotrafiban hydrochloride (USAN)
D05267 Orbofiban acetate (USAN)
D05597 Prasugrel hydrochloride (JAN/USAN)
D05772 Roxifiban acetate (USAN)
D06213 Treprostinil (JAN/USAN/INN)
D06280 Vapiprost hydrochloride (JAN/USAN)
D06335 Xemilofiban hydrochloride (USAN)
D08628 Treprostinil monosodium salt
D08983 Regrelor disodium (USAN)
D09017 Ticagrelor (JAN/USAN/INN)
D09348 Fostamatinib disodium (USAN)
D09572 Riociguat (JAN/USAN/INN)
D09608 Elinogrel potassium (USAN)
D09766 Vorapaxar sulfate (JAN/USAN)
D09994 Selexipag (JAN/USAN/INN)
D10430 Treprostinil diolamine (USAN)
D10758 Turoctocog alfa pegol (genetical recombination) (JAN)
D10823 Clopidogrel hydrochloride
D10893 Acalabrutinib (JAN/USAN/INN)
D11051 Vericiguat (JAN/USAN/INN)
D11070 Tirabrutinib hydrochloride (JAN/USAN)
D11160 Caplacizumab (USAN/INN)
D11209 Entospletinib (USAN/INN)
D11428 Vecabrutinib (USAN/INN)
D11457 Fenebrutinib (USAN/INN)
D11502 Vecabrutinib succinate (USAN)
D11720 Acalabrutinib maleate (USAN)
D11790 Mivavotinib citrate (USAN)
D12050 Pirtobrutinib (JAN/USAN)
D12160 Orelabrutinib (USAN/INN)
D12163 Zalunfiban acetate (USAN)
D12383 Edralbrutinib (USAN/INN)
D12504 Nemtabrutinib (USAN/INN)
D12594 Tirabrutinib (USAN/INN)
D12629 Treprostinil phosphate (USAN)
D12704 Acalabrutinib maleate hydrate (JAN)
Homo sapiens (human) [GN:
2149 F2R; coagulation factor II thrombin receptor [KO: K03914]
9002 F2RL3; F2R like thrombin or trypsin receptor 3 [KO: K04236]
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: 188.8.131.52]
9475 ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO: K17388] [EC: 184.108.40.206]
4659 PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO: K06270]
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]
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]
3674 ITGA2B; integrin subunit alpha 2b [KO: K06476]
83706 FERMT3; FERM domain containing kindlin 3 [KO: K17084]
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]
5294 PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO: K21289] [EC: 220.127.116.11]
23533 PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO: K21290]
146850 PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO: K21290]
7408 VASP; vasodilator stimulated phosphoprotein [KO: K06274]
2909 ARHGAP35; Rho GTPase activating protein 35 [KO: K05732]
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]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO: K00922] [EC: 18.104.22.168]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO: K00922] [EC: 22.214.171.124]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO: K00922] [EC: 126.96.36.199]
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]
3937 LCP2; lymphocyte cytosolic protein 2 [KO: K07361]
2811 GP1BA; glycoprotein Ib platelet subunit alpha [KO: K06261]
2812 GP1BB; glycoprotein Ib platelet subunit beta [KO: K06262]
8773 SNAP23; synaptosome associated protein 23 [KO: K08508]
8673 VAMP8; vesicle associated membrane protein 8 [KO: K08512]
C01245 D-myo-Inositol 1,4,5-trisphosphate
Li Z, Delaney MK, O'Brien KA, Du X
Signaling during platelet adhesion and activation.
Broos K, De Meyer SF, Feys HB, Vanhoorelbeke K, Deckmyn H
Blood platelet biochemistry.
Jurk K, Kehrel BE
Platelets: physiology and biochemistry.
Activation of platelet function through G protein-coupled receptors.
Varga-Szabo D, Pleines I, Nieswandt B
Cell adhesion mechanisms in platelets.
Yin H, Liu J, Li Z, Berndt MC, Lowell CA, Du X
Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway.
Bergmeier W, Stefanini L
Novel molecules in calcium signaling in platelets.
Cifuni SM, Wagner DD, Bergmeier W
CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets.
Heemskerk JW, Mattheij NJ, Cosemans JM
Platelet-based coagulation: different populations, different functions.
Rivera J, Lozano ML, Navarro-Nunez L, Vicente V
Platelet receptors and signaling in the dynamics of thrombus formation.
Banno A, Ginsberg MH
Angiolillo DJ, Ferreiro JL
Platelet adenosine diphosphate P2Y12 receptor antagonism: benefits and limitations of current treatment strategies and future directions.
Mechanisms of Platelet Activation and Integrin alphaIIbeta3.
Harper MT, Poole AW
Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation.
Fitch-Tewfik JL, Flaumenhaft R
Platelet granule exocytosis: a comparison with chromaffin cells.
Boylan B, Gao C, Rathore V, Gill JC, Newman DK, Newman PJ
Identification of FcgammaRIIa as the ITAM-bearing receptor mediating alphaIIbbeta3 outside-in integrin signaling in human platelets.
hsa04610 Complement and coagulation cascades
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