KEGG   PATHWAY: bom04611
Entry
bom04611                    Pathway                                
Name
Platelet activation - Bos mutus (wild yak)
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
bom04611  Platelet activation
bom04611

Other DBs
GO: 0030168
Organism
Bos mutus (wild yak) [GN:bom]
Gene
102268062  TBXA2R; thromboxane A2 receptor [KO:K04264]
102271164  F2; coagulation factor II, thrombin [KO:K01313] [EC:3.4.21.5]
102272347  F2R; coagulation factor II thrombin receptor [KO:K03914]
102270079  F2RL3; F2R like thrombin/trypsin receptor 3 [KO:K04236]
102275435  GNA13; G protein subunit alpha 13 [KO:K04639]
102271873  ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
102277776  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
102280554  RHOA; ras homolog family member A [KO:K04513]
102284712  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
102267122  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
102270793  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102275429  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102266876  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102268036  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
102269444  myosin regulatory light polypeptide 9 [KO:K12757]
102268971  MYL12B; myosin regulatory light chain 12B [KO:K12757]
102278561  P2RX1; purinergic receptor P2X 1 [KO:K05215]
102274230  ORAI1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
102269088  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102269013  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102271039  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102271938  STIM1; stromal interaction molecule 1 [KO:K16059]
102264349  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
102275601  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
102276600  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
102269080  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
102266465  P2RY1; purinergic receptor P2Y1 [KO:K04270]
102287414  GNAQ; G protein subunit alpha q [KO:K04634]
102264989  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102278948  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102273347  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102276260  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102269695  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
102268043  PRKCI; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
102272711  RASGRP1; RAS guanyl releasing protein 1 [KO:K04350]
102264750  RASGRP2; RAS guanyl releasing protein 2 [KO:K12361]
102286224  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
102269967  ras-related protein Rap-1b-like [KO:K07836]
102265384  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
102277019  ras-related protein Rap-1b-like [KO:K07836]
102285376  APBB1IP; amyloid beta precursor protein binding family B member 1 interacting protein [KO:K17704]
102270446  TLN2; talin 2 [KO:K06271]
102276194  TLN1; talin 1 [KO:K06271]
102275560  ITGA2B; integrin subunit alpha 2b [KO:K06476]
102268918  ITGB3; integrin subunit beta 3 [KO:K06493]
102283765  FERMT3; fermitin family member 3 [KO:K17084]
102286209  FGA; fibrinogen alpha chain [KO:K03903]
102284525  FGB; fibrinogen beta chain [KO:K03904]
102285182  FGG; fibrinogen gamma chain [KO:K03905]
102279592  P2RY12; purinergic receptor P2Y12 [KO:K04298]
102285228  GNAI3; G protein subunit alpha i3 [KO:K04630]
102274651  GNAI2; G protein subunit alpha i2 [KO:K04630]
102273920  GNAI1; G protein subunit alpha i1 [KO:K04630]
102267116  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102274117  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102282732  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102286168  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102276460  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102265325  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102266966  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102272964  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102285642  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102282194  PTGIR; prostaglandin I2 (prostacyclin) receptor (IP) [KO:K04263]
102266153  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102286123  neuroendocrine secretory protein 55 [KO:K04632]
102277419  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102282596  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102279608  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102281757  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102269124  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102281273  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
102285564  ACTG1; actin gamma 1 [KO:K05692]
102286048  ACTB; actin beta [KO:K05692]
102284506  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102280880  ARHGAP35; Rho GTPase activating protein 35 [KO:K05732]
102274112  low affinity immunoglobulin gamma Fc region receptor II [KO:K06472]
102271008  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
102265105  COL1A1; collagen type I alpha 1 chain [KO:K06236]
102267202  COL1A2; collagen type I alpha 2 chain [KO:K06236]
102279325  COL3A1; collagen type III alpha 1 chain [KO:K19720]
102272972  GP6; glycoprotein VI platelet [KO:K06264]
102274435  FCER1G; Fc fragment of IgE receptor Ig [KO:K07983]
102276698  LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
102284015  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
102281399  ITGA2; integrin subunit alpha 2 [KO:K06481]
102273972  ITGB1; integrin subunit beta 1 [KO:K05719]
102274553  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102274461  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102277548  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102266922  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102280296  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102286868  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102286689  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
102285300  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102284433  BTK; Bruton tyrosine kinase [KO:K07370] [EC:2.7.10.2]
102282731  VWF; von Willebrand factor [KO:K03900]
102266211  GP5; glycoprotein V platelet [KO:K06260]
102266317  GP1BA; glycoprotein Ib platelet alpha subunit [KO:K06261]
102275199  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102265427  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102283212  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102267556  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102281834  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
102280817  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
102282106  GUCY1B3; guanylate cyclase 1 soluble subunit beta [KO:K12319] [EC:4.6.1.2]
102285947  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
102279305  PRKG1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
102269763  PRKG2; protein kinase, cGMP-dependent, type II [KO:K19477] [EC:2.7.11.12]
102270503  cGMP-dependent protein kinase 2-like [KO:K19477] [EC:2.7.11.12]
102271030  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102271320  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
106701244  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102285848  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102272368  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102284931  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102271639  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102282019  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
102282862  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102283142  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
102282579  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
102287995  PTGS1; prostaglandin-endoperoxide synthase 1 [KO:K00509] [EC:1.14.99.1]
102269002  TBXAS1; thromboxane A synthase 1 [KO:K01832] [EC:5.3.99.5]
102286687  SNAP23; synaptosome associated protein 23 [KO:K08508]
102277569  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Banno A, Ginsberg MH
  Title
Integrin activation.
  Journal
Biochem Soc Trans 36:229-34 (2008)
DOI:10.1042/BST0360229
Reference
  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
  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
  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
  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
  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
bom00590  Arachidonic acid metabolism
bom04015  Rap1 signaling pathway
bom04020  Calcium signaling pathway
bom04151  PI3K-Akt signaling pathway
bom04610  Complement and coagulation cascades
bom05211  Renal cell carcinoma
KO pathway
ko04611   

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