KEGG   PATHWAY: epz04611
Entry
epz04611                    Pathway                                
Name
Platelet activation - Equus przewalskii (Przewalski's horse)
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
epz04611  Platelet activation
epz04611

Other DBs
GO: 0030168
Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103544870  TBXA2R; thromboxane A2 receptor [KO:K04264]
103566907  F2; coagulation factor II, thrombin [KO:K01313] [EC:3.4.21.5]
103540011  F2R; coagulation factor II thrombin receptor [KO:K03914]
103543162  F2RL3; F2R like thrombin/trypsin receptor 3 [KO:K04236]
103553497  GNA13; G protein subunit alpha 13 [KO:K04639]
103563986  ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
103546845  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
103553409  RHOA; ras homolog family member A [KO:K04513]
103552805  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
103557393  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.39]
103560150  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
103541647  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
103549472  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
103549928  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
103559953  myosin regulatory light chain 12B [KO:K12757]
103559954  myosin regulatory light polypeptide 9 [KO:K12757]
103558306  P2RX1; purinergic receptor P2X 1 [KO:K05215]
103541373  ORAI1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
103550297  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103546630  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103548182  inositol 1,4,5-trisphosphate receptor type 2-like [KO:K04959]
103564724  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103558525  STIM1; stromal interaction molecule 1 [KO:K16059]
103548123  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
103547465  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
103559162  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
103551781  P2RY1; purinergic receptor P2Y1 [KO:K04270]
103553450  GNAQ; G protein subunit alpha q [KO:K04634]
103562440  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103559733  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103561633  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103542193  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103559872  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
103553747  PRKCI; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
103560184  RASGRP1; RAS guanyl releasing protein 1 [KO:K04350]
103565063  RASGRP2; RAS guanyl releasing protein 2 [KO:K12361]
103547802  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
103558687  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
103565481  APBB1IP; amyloid beta precursor protein binding family B member 1 interacting protein [KO:K17704]
103552581  TLN2; talin 2 [KO:K06271]
103560301  TLN1; talin 1 [KO:K06271]
103551206  ITGA2B; integrin subunit alpha 2b [KO:K06476]
103560746  ITGB3; integrin subunit beta 3 [KO:K06493]
103542358  FERMT3; fermitin family member 3 [KO:K17084]
103553817  FGA; fibrinogen alpha chain [KO:K03903]
103553816  FGB; fibrinogen beta chain [KO:K03904]
103553818  FGG; fibrinogen gamma chain [KO:K03905]
103551471  P2RY12; purinergic receptor P2Y12 [KO:K04298]
103552141  guanine nucleotide-binding protein G(i) subunit alpha-1-like [KO:K04630]
103553052  GNAI3; G protein subunit alpha i3 [KO:K04630]
103557343  GNAI2; G protein subunit alpha i2 [KO:K04630]
103550430  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103562505  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
103547823  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103561050  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103563830  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103563634  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103556685  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103565019  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
103567623  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103553014  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103542501  PTGIR; prostaglandin I2 (prostacyclin) receptor (IP) [KO:K04263]
103565402  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103547036  neuroendocrine secretory protein 55 [KO:K04632]
103557800  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
103564501  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
103564503  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
103557289  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103565953  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103566352  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
103551082  ACTG1; actin gamma 1 [KO:K05692]
103547895  ACTB; actin beta [KO:K05692]
103560907  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103560716  ARHGAP35; Rho GTPase activating protein 35 [KO:K05732]
103540857  low affinity immunoglobulin gamma Fc region receptor II-a-like [KO:K06472]
103540858  FCGR2A; Fc fragment of IgG receptor IIa [KO:K06472]
103565660  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
103549571  COL1A1; collagen type I alpha 1 chain [KO:K06236]
103553631  COL1A2; collagen type I alpha 2 chain [KO:K06236]
103542003  COL3A1; collagen type III alpha 1 chain [KO:K19720]
103554722  GP6; glycoprotein VI platelet [KO:K06264]
103554497  high affinity immunoglobulin epsilon receptor subunit gamma-like [KO:K07983]
103559990  FCER1G; Fc fragment of IgE receptor Ig [KO:K07983]
103552502  LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
103547543  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
103558080  ITGA2; integrin subunit alpha 2 [KO:K06481]
103565316  ITGB1; integrin subunit beta 1 [KO:K05719]
103549076  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103554655  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform-like [KO:K00922] [EC:2.7.1.153]
103552150  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103548220  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103551868  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103561550  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103541962  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
103558212  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
103542797  BTK; Bruton tyrosine kinase [KO:K07370] [EC:2.7.10.2]
103546989  VWF; von Willebrand factor [KO:K03900]
103560749  GP5; glycoprotein V platelet [KO:K06260]
103560661  GP1BA; glycoprotein Ib platelet alpha subunit [KO:K06261]
103567568  GP1BB; glycoprotein Ib platelet beta subunit [KO:K06262]
103543013  GP9; glycoprotein IX platelet [KO:K06263]
103565346  ADAMTS13; ADAM metallopeptidase with thrombospondin type 1 motif 13 [KO:K08627] [EC:3.4.24.87]
103560497  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103540249  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103555421  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103540937  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
103563826  guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
103562610  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
103551994  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
103562608  GUCY1B3; guanylate cyclase 1 soluble subunit beta [KO:K12319] [EC:4.6.1.2]
103549039  PRKG2; protein kinase, cGMP-dependent, type II [KO:K19477] [EC:2.7.11.12]
103565534  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103563198  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103559485  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103559491  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103547261  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103562408  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103549946  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
103549947  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
103549950  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
103549953  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
103560072  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
103555394  PTGS1; prostaglandin-endoperoxide synthase 1 [KO:K00509] [EC:1.14.99.1]
103556299  TBXAS1; thromboxane A synthase 1 [KO:K01832] [EC:5.3.99.5]
103549937  SNAP23; synaptosome associated protein 23 [KO:K08508]
103548261  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
epz00590  Arachidonic acid metabolism
epz04015  Rap1 signaling pathway
epz04020  Calcium signaling pathway
epz04151  PI3K-Akt signaling pathway
epz04610  Complement and coagulation cascades
epz05211  Renal cell carcinoma
KO pathway
ko04611   
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