KEGG   PATHWAY: ko04611
Entry
ko04611                     Pathway                                
Name
Platelet activation
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
ko04611  Platelet activation
ko04611

Other DBs
GO: 0030168
Orthology
K00509  PTGS1, COX1; prostaglandin-endoperoxide synthase 1 [EC:1.14.99.1]
K00907  MYLK; myosin-light-chain kinase [EC:2.7.11.18]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01313  F2; coagulation factor II (thrombin) [EC:3.4.21.5]
K01832  TBXAS1, CYP5A; thromboxane-A synthase [EC:5.3.99.5]
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03900  VWF; von Willebrand factor
K03903  FGA; fibrinogen alpha chain
K03904  FGB; fibrinogen beta chain
K03905  FGG; fibrinogen gamma chain
K03914  F2R, PAR1; coagulation factor II (thrombin) receptor
K04236  F2RL3, PAR4; coagulation factor II (thrombin) receptor-like 3
K04263  PTGIR; prostacyclin receptor
K04264  TBXA2R; thromboxane A2 receptor
K04270  P2RY1; P2Y purinoceptor 1
K04298  P2RY12; P2Y purinoceptor 12
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04350  RASGRP1; RAS guanyl-releasing protein 1
K04353  RAP1A; Ras-related protein Rap-1A
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04441  P38; p38 MAP kinase [EC:2.7.11.24]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04513  RHOA; Ras homolog gene family, member A
K04514  ROCK1; Rho-associated protein kinase 1 [EC:2.7.11.39]
K04630  GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04632  GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04639  GNA13; guanine nucleotide-binding protein subunit alpha-13
K04958  ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959  ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960  ITPR3; inositol 1,4,5-triphosphate receptor type 3
K05215  P2RX1; P2X purinoceptor 1
K05692  ACTB_G1; actin beta/gamma 1
K05703  FYN; tyrosine-protein kinase Fyn [EC:2.7.10.2]
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K05719  ITGB1, CD29; integrin beta 1
K05732  ARHGAP35, GRLF1; glucocorticoid receptor DNA-binding factor 1
K05854  LYN; tyrosine-protein kinase Lyn [EC:2.7.10.2]
K05855  SYK; spleen tyrosine kinase [EC:2.7.10.2]
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05859  PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K06069  PRKCI; atypical protein kinase C iota type [EC:2.7.11.13]
K06236  COL1A; collagen type I alpha
K06260  GP5, CD42d; platelet glycoprotein V
K06261  GP1BA, CD42b; platelet glycoprotein Ib alpha chain
K06262  GP1BB, CD42c; platelet glycoprotein Ib beta chain
K06263  GP9, CD42a; platelet glycoprotein IX
K06264  GP6; platelet glycoprotein VI
K06269  PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K06270  PPP1R12A, MYPT1; protein phosphatase 1 regulatory subunit 12A
K06271  TLN; talin
K06274  VASP; vasodilator-stimulated phosphoprotein
K06472  FCGR2A, CD32; low affinity immunoglobulin gamma Fc receptor II-a
K06476  ITGA2B, CD41; integrin alpha 2B
K06481  ITGA2, CD49b; integrin alpha 2
K06493  ITGB3, CD61; integrin beta 3
K07361  LCP2; lymphocyte cytosolic protein 2
K07370  BTK; Bruton agammaglobulinemia tyrosine kinase [EC:2.7.10.2]
K07376  PRKG1; cGMP-dependent protein kinase 1 [EC:2.7.11.12]
K07532  ARHGEF12, LARG; Rho guanine nucleotide exchange factor 12
K07836  RAP1B; Ras-related protein Rap-1B
K07983  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma
K08041  ADCY1; adenylate cyclase 1 [EC:4.6.1.1]
K08042  ADCY2; adenylate cyclase 2 [EC:4.6.1.1]
K08043  ADCY3; adenylate cyclase 3 [EC:4.6.1.1]
K08044  ADCY4; adenylate cyclase 4 [EC:4.6.1.1]
K08045  ADCY5; adenylate cyclase 5 [EC:4.6.1.1]
K08046  ADCY6; adenylate cyclase 6 [EC:4.6.1.1]
K08047  ADCY7; adenylate cyclase 7 [EC:4.6.1.1]
K08048  ADCY8; adenylate cyclase 8 [EC:4.6.1.1]
K08049  ADCY9; adenylate cyclase 9 [EC:4.6.1.1]
K08508  SNAP23; synaptosomal-associated protein 23
K08512  VAMP8; vesicle-associated membrane protein 8
K08627  ADAMTS13; a disintegrin and metalloproteinase with thrombospondin motifs 13 [EC:3.4.24.87]
K12318  GUCY1A; guanylate cyclase soluble subunit alpha [EC:4.6.1.2]
K12319  GUCY1B; guanylate cyclase soluble subunit beta [EC:4.6.1.2]
K12330  ARHGEF1; Rho guanine nucleotide exchange factor 1
K12361  RASGRP2; RAS guanyl-releasing protein 2
K12757  MYL12; myosin regulatory light chain 12
K13242  NOS3; nitric-oxide synthase, endothelial [EC:1.14.13.39]
K16056  ORAI1; calcium release-activated calcium channel protein 1
K16059  STIM1; stromal interaction molecule 1
K16342  PLA2G4, CPLA2; cytosolic phospholipase A2 [EC:3.1.1.4]
K17084  FERMT3, KIND3; kindlin 3
K17388  ROCK2; Rho-associated protein kinase 2 [EC:2.7.11.39]
K17704  APBB1IP, RIAM; amyloid beta A4 precursor protein-binding family B member 1-interacting protein
K18952  PRKCZ; atypical protein kinase C zeta type [EC:2.7.11.13]
K19477  PRKG2; cGMP-dependent protein kinase 2 [EC:2.7.11.12]
K19720  COL3A; collagen type III alpha
K21289  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:2.7.1.153]
K21290  PIK3R5_6; phosphoinositide-3-kinase regulatory subunit 5/6
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
ko00590  Arachidonic acid metabolism
ko04015  Rap1 signaling pathway
ko04020  Calcium signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04610  Complement and coagulation cascades
ko05211  Renal cell carcinoma

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