KEGG   PATHWAY: panu04611
Entry
panu04611                   Pathway                                
Name
Platelet activation - Papio anubis (olive baboon)
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
panu04611  Platelet activation
panu04611

Other DBs
GO: 0030168
Organism
Papio anubis (olive baboon) [GN:panu]
Gene
100137599  RASGRP2; RAS guanyl-releasing protein 2 [KO:K12361]
100381179  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100510873  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X4 [KO:K02649]
100997319  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100997634  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100997671  ROCK1; rho-associated protein kinase 1 isoform X2 [KO:K04514] [EC:2.7.11.39]
100998237  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100998763  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100998840  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
100999120  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X5 [KO:K05858] [EC:3.1.4.11]
101000142  [KO:K16342] [EC:3.1.1.4]
101000402  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101000692  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
101000833  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101001103  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
101001272  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101001384  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
101002054  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
101002278  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101002393  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101002468  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
101002819  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
101002971  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101003099  ROCK2; rho-associated protein kinase 2 isoform X5 [KO:K17388] [EC:2.7.11.39]
101003685  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
101003717  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101004091  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
101004198  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
101004206  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
101004255  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
101004325  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
101004530  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
101004976  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101005052  ITGB1; integrin beta-1 isoform X2 [KO:K05719]
101005380  SNAP23; synaptosomal-associated protein 23 isoform X2 [KO:K08508]
101005809  COL1A2; collagen alpha-2(I) chain [KO:K06236]
101006469  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101006754  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
101006756  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101006785  [KO:K04632]
101006944  [KO:K12319] [EC:4.6.1.2]
101007115  ADCY8; adenylate cyclase type 8 isoform X3 [KO:K08048] [EC:4.6.1.1]
101007177  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
101007440  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
101007826  [KO:K17704]
101008275  BTK; tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
101008458  GP5; platelet glycoprotein V [KO:K06260]
101008699  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101008785  ADCY6; adenylate cyclase type 6 isoform X3 [KO:K08046] [EC:4.6.1.1]
101009395  ITGA2B; integrin alpha-IIb [KO:K06476]
101009613  [KO:K05215]
101009767  [KO:K06271]
101009922  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
101009981  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101010000  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
101010815  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
101011013  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
101011187  PTGIR; prostacyclin receptor [KO:K04263]
101011251  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101011420  GP6; platelet glycoprotein VI [KO:K06264]
101011576  VWF; von Willebrand factor isoform X1 [KO:K03900]
101012041  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101012095  ITGB3; integrin beta-3 [KO:K06493]
101012839  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
101012903  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101013495  RAP1B; ras-related protein Rap-1b isoform X1 [KO:K07836]
101013535  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
101013662  P2RY1; P2Y purinoceptor 1 [KO:K04270]
101013796  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X5 [KO:K12330]
101014159  ITGA2; integrin alpha-2 [KO:K06481]
101014342  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
101014715  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
101014828  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101014878  F2R; proteinase-activated receptor 1 [KO:K03914]
101015306  FERMT3; fermitin family homolog 3 isoform X1 [KO:K17084]
101015341  [KO:K12757]
101016118  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X2 [KO:K06269] [EC:3.1.3.16]
101016648  [KO:K12757]
101016979  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
101017243  FGB; fibrinogen beta chain [KO:K03904]
101017317  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101017602  FGA; LOW QUALITY PROTEIN: fibrinogen alpha chain [KO:K03903]
101017958  FGG; fibrinogen gamma chain isoform X2 [KO:K03905]
101017970  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
101018542  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
101018650  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 [KO:K08627] [EC:3.4.24.87]
101018714  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
101018767  TLN1; talin-1 isoform X2 [KO:K06271]
101019577  P2RY12; P2Y purinoceptor 12 [KO:K04298]
101020071  TBXAS1; thromboxane-A synthase isoform X4 [KO:K01832] [EC:5.3.99.5]
101020203  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
101020378  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
101020528  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
101020553  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
101021139  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
101021299  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X3 [KO:K06270]
101021599  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
101022395  STIM1; stromal interaction molecule 1 isoform X3 [KO:K16059]
101023014  F2RL3; proteinase-activated receptor 4 [KO:K04236]
101023112  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
101023200  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101023431  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
101023586  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
101023919  VAMP8; vesicle-associated membrane protein 8 [KO:K08512]
101024177  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
101024189  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101024208  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
101024528  GP1BA; LOW QUALITY PROTEIN: platelet glycoprotein Ib alpha chain [KO:K06261]
101024771  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101024880  SYK; tyrosine-protein kinase SYK isoform X6 [KO:K05855] [EC:2.7.10.2]
101024888  NOS3; LOW QUALITY PROTEIN: nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
101025072  GP9; platelet glycoprotein IX [KO:K06263]
101025097  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
101025205  COL3A1; collagen alpha-1(III) chain [KO:K19720]
101025530  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101025668  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101025874  LYN; tyrosine-protein kinase Lyn isoform X2 [KO:K05854] [EC:2.7.10.2]
101025964  TBXA2R; LOW QUALITY PROTEIN: thromboxane A2 receptor [KO:K04264]
101026142  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
101026251  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X15 [KO:K04345] [EC:2.7.11.11]
101026282  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
101026869  ACTB; actin, cytoplasmic 1 [KO:K05692]
103884727  GUCY1A1; guanylate cyclase soluble subunit alpha-1 isoform X1 [KO:K12318] [EC:4.6.1.2]
103887915  [KO:K04632]
103888219  GP1BB; platelet glycoprotein Ib beta chain isoform X2 [KO:K06262]
110741987  [KO:K05692]
116268521  [KO:K06271]
116270998  P2RX1; P2X purinoceptor 1 [KO:K05215]
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
panu00590  Arachidonic acid metabolism
panu04015  Rap1 signaling pathway
panu04020  Calcium signaling pathway
panu04151  PI3K-Akt signaling pathway
panu04610  Complement and coagulation cascades
panu05211  Renal cell carcinoma
KO pathway
ko04611   

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