KEGG   PATHWAY: csab04611
Entry
csab04611                   Pathway                                
Name
Platelet activation - Chlorocebus sabaeus (green monkey)
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
csab04611  Platelet activation
csab04611

Other DBs
GO: 0030168
Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103214549  [KO:K12319] [EC:4.6.1.2]
103214981  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
103215020  [KO:K05692]
103215555  [KO:K07836]
103216192  PRKG1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
103217237  [KO:K05692]
103217501  COL3A1; collagen type III alpha 1 chain [KO:K19720]
103218442  VWF; von Willebrand factor [KO:K03900]
103218776  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103218890  PTGS1; prostaglandin-endoperoxide synthase 1 [KO:K00509] [EC:1.14.99.1]
103218909  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
103219208  TLN1; talin 1 [KO:K06271]
103219323  [KO:K05692]
103219549  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
103219624  GNAQ; G protein subunit alpha q [KO:K04634]
103219736  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
103219942  VAMP8; vesicle associated membrane protein 8 [KO:K08512]
103220572  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
103220665  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103220805  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.39]
103221212  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103221285  ITGA2; integrin subunit alpha 2 [KO:K06481]
103221331  PRKCI; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
103221595  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103221596  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103221654  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103222295  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
103222594  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103222670  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
103222701  MYL12B; myosin light chain 12B [KO:K12757]
103222703  MYL12A; myosin light chain 12A [KO:K12757]
103222941  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103222996  GP1BB; glycoprotein Ib platelet beta subunit [KO:K06262]
103223358  F2R; coagulation factor II thrombin receptor [KO:K03914]
103223551  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103223553  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103223676  FCGR2A; Fc fragment of IgG receptor IIa [KO:K06472]
103223689  FCER1G; Fc fragment of IgE receptor Ig [KO:K07983]
103224221  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
103224284  GNAI3; G protein subunit alpha i3 [KO:K04630]
103224540  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103224900  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103225637  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103225772  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
103226115  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103226536  COL1A2; collagen type I alpha 2 chain [KO:K06236]
103226652  GNAI1; G protein subunit alpha i1 [KO:K04630]
103226710  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
103227005  TBXAS1; thromboxane A synthase 1 [KO:K01832] [EC:5.3.99.5]
103227233  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
103227576  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103227629  RHOA; ras homolog family member A [KO:K04513]
103227664  GNAI2; G protein subunit alpha i2 [KO:K04630]
103227941  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103228081  GP9; glycoprotein IX platelet [KO:K06263]
103228167  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
103228169  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103228726  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103229784  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103230418  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
103230532  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103230823  [KO:K05692]
103230869  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103232215  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
103232359  BTK; Bruton tyrosine kinase [KO:K07370] [EC:2.7.10.2]
103232667  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103233086  RASGRP2; RAS guanyl releasing protein 2 [KO:K12361]
103233299  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103233371  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
103233401  FERMT3; fermitin family member 3 [KO:K17084]
103233689  TBXA2R; thromboxane A2 receptor [KO:K04264]
103234119  F2RL3; F2R like thrombin/trypsin receptor 3 [KO:K04236]
103234377  [KO:K04345] [EC:2.7.11.11]
103234391  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103234702  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103234745  ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
103234868  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
103234917  PTGIR; prostaglandin I2 (prostacyclin) receptor (IP) [KO:K04263]
103234927  ARHGAP35; Rho GTPase activating protein 35 [KO:K05732]
103235286  GP6; glycoprotein VI platelet [KO:K06264]
103235528  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
103235875  PRKG2; protein kinase, cGMP-dependent, type II [KO:K19477] [EC:2.7.11.12]
103236354  [KO:K01313] [EC:3.4.21.5]
103236419  FGB; fibrinogen beta chain [KO:K03904]
103236420  FGA; fibrinogen alpha chain [KO:K03903]
103236421  FGG; fibrinogen gamma chain [KO:K03905]
103236428  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
103236429  GUCY1B3; guanylate cyclase 1 soluble subunit beta [KO:K12319] [EC:4.6.1.2]
103236819  LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
103237447  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103238030  APBB1IP; amyloid beta precursor protein binding family B member 1 interacting protein [KO:K17704]
103238098  ITGB1; integrin subunit beta 1 [KO:K05719]
103238242  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103238680  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
103238782  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
103239286  ORAI1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
103239526  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
103239684  ADAMTS13; ADAM metallopeptidase with thrombospondin type 1 motif 13 [KO:K08627] [EC:3.4.24.87]
103240563  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
103240948  [KO:K05692]
103241450  P2RY1; purinergic receptor P2Y1 [KO:K04270]
103241467  P2RY12; purinergic receptor P2Y12 [KO:K04298]
103241599  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103241942  GP5; glycoprotein V platelet [KO:K06260]
103242171  P2RX1; purinergic receptor P2X 1 [KO:K05215]
103242366  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
103242368  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
103242552  GP1BA; glycoprotein Ib platelet alpha subunit [KO:K06261]
103242943  COL1A1; collagen type I alpha 1 chain [KO:K06236]
103243186  GNA13; G protein subunit alpha 13 [KO:K04639]
103243277  ITGB3; integrin subunit beta 3 [KO:K06493]
103243322  ITGA2B; integrin subunit alpha 2b [KO:K06476]
103243499  [KO:K04632]
103243509  GNAS; GNAS complex locus [KO:K04632]
103243719  ACTG1; actin gamma 1 [KO:K05692]
103244954  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
103245518  TLN2; talin 2 [KO:K06271]
103245766  SNAP23; synaptosome associated protein 23 [KO:K08508]
103245774  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
103245776  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
103245777  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
103245842  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103245866  RASGRP1; RAS guanyl releasing protein 1 [KO:K04350]
103246100  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
103246384  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103246591  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103246657  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103246953  ACTB; actin beta [KO:K05692]
103247973  STIM1; stromal interaction molecule 1 [KO:K16059]
103248051  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
103248387  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
103248653  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
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
csab00590  Arachidonic acid metabolism
csab04015  Rap1 signaling pathway
csab04020  Calcium signaling pathway
csab04151  PI3K-Akt signaling pathway
csab04610  Complement and coagulation cascades
csab05211  Renal cell carcinoma
KO pathway
ko04611   

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