KEGG   PATHWAY: sbq04611
Entry
sbq04611                    Pathway                                
Name
Platelet activation - Saimiri boliviensis boliviensis (Bolivian squirrel 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
sbq04611  Platelet activation
sbq04611

Other DBs
GO: 0030168
Organism
Saimiri boliviensis boliviensis (Bolivian squirrel monkey) [GN:sbq]
Gene
101049318  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
101048036  F2R; proteinase-activated receptor 1 [KO:K03914]
101029013  F2RL3; proteinase-activated receptor 4 [KO:K04236]
101034540  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
101043419  ARHGEF1; rho guanine nucleotide exchange factor 1 [KO:K12330]
101040423  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
101052068  RHOA; transforming protein RhoA [KO:K04513]
104650592  ras-like GTP-binding protein O-RHO [KO:K04513]
104652261  RHOC; rho-related GTP-binding protein RhoC [KO:K04513]
101051787  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
101028677  LOW QUALITY PROTEIN: rho-associated protein kinase 1-like [KO:K04514] [EC:2.7.11.1]
101039371  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
101030626  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
101050671  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101048497  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
101048398  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101034840  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
101053931  myosin regulatory light polypeptide 9-like isoform X1 [KO:K12757]
101029210  myosin regulatory light polypeptide 9-like isoform X1 [KO:K12757]
101033130  myosin regulatory light polypeptide 9 isoform X2 [KO:K12757]
101049446  uncharacterized protein LOC101049446 [KO:K12757]
101034335  P2RX1; P2X purinoceptor 1 [KO:K05215]
101044294  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
101029556  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101049881  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101048916  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101047752  STIM1; stromal interaction molecule 1 isoform X3 [KO:K16059]
101038668  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
101049056  MYLK4; myosin light chain kinase family member 4 isoform X2 [KO:K00907] [EC:2.7.11.18]
101050910  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
101029220  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
101050405  P2RY1; P2Y purinoceptor 1 [KO:K04270]
101051855  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101046851  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
101047168  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
101052271  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101029401  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101039978  PRKCZ; protein kinase C zeta type isoform X4 [KO:K18952] [EC:2.7.11.13]
101037993  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
101030982  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
101053574  RASGRP2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
101048450  RAP1A; ras-related protein Rap-1A [KO:K04353]
101036065  RAP1B; ras-related protein Rap-1b [KO:K07836]
101054184  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
101038605  TLN2; talin-2 isoform X1 [KO:K06271]
101050642  TLN1; talin-1 isoform X4 [KO:K06271]
101031876  ITGA2B; integrin alpha-IIb [KO:K06476]
101049562  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
101046245  FERMT3; fermitin family homolog 3 [KO:K17084]
101043642  FGA; LOW QUALITY PROTEIN: fibrinogen alpha chain [KO:K03903]
101043955  FGB; fibrinogen beta chain [KO:K03904]
101043315  FGG; fibrinogen gamma chain [KO:K03905]
101028678  P2RY12; P2Y purinoceptor 12 [KO:K04298]
101042629  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101041681  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101032105  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101027981  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101043334  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101040601  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101044688  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
101049747  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
101037803  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
101032672  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101034552  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
101052034  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
101029640  PTGIR; prostacyclin receptor [KO:K04263]
101043452  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
104652116  neuroendocrine secretory protein 55 [KO:K04632]
101028650  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
101031169  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
101033790  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
101034152  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
101036705  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101043989  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
101047300  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101049548  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
101037287  ACTB; actin, cytoplasmic 1 [KO:K05692]
101050060  actin, cytoplasmic 2-like isoform X1 [KO:K05692]
101049910  ACTG1; actin, cytoplasmic 2 [KO:K05692]
104651678  actin, cytoplasmic 1-like [KO:K05692]
101051959  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101032805  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
101040113  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
101031617  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
101051510  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
101045518  COL1A2; collagen alpha-2(I) chain [KO:K06236]
101039232  COL3A1; collagen alpha-1(III) chain [KO:K19720]
101050914  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
101036887  LYN; tyrosine-protein kinase Lyn isoform X2 [KO:K05854] [EC:2.7.10.2]
101051746  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101041311  ITGA2; integrin alpha-2 [KO:K06481]
101040620  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
101029768  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101052779  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101027982  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101032496  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101033359  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101050592  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101050038  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
101030999  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101054345  BTK; LOW QUALITY PROTEIN: tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
101044155  VWF; von Willebrand factor [KO:K03900]
101049885  GP5; platelet glycoprotein V [KO:K06260]
101033397  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
104650035  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
101044256  GP9; platelet glycoprotein IX [KO:K06263]
101034861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101045714  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101040766  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101034220  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
101040779  GUCY1A3; guanylate cyclase soluble subunit alpha-3 isoform X1 [KO:K12318] [EC:4.6.1.2]
101040955  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
101027848  guanylate cyclase soluble subunit beta-2 [KO:K12319] [EC:4.6.1.2]
101040246  GUCY1B3; guanylate cyclase soluble subunit beta-1 isoform X2 [KO:K12319] [EC:4.6.1.2]
101043597  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
101033123  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
101037444  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101044137  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101040899  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101052690  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101038546  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101043202  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101038256  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
101054434  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
101036859  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
101037291  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
101037621  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
101033759  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
101049596  TBXAS1; thromboxane-A synthase [KO:K01832] [EC:5.3.99.5]
101043761  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
101030599  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
sbq00590  Arachidonic acid metabolism
sbq04015  Rap1 signaling pathway
sbq04020  Calcium signaling pathway
sbq04151  PI3K-Akt signaling pathway
sbq04610  Complement and coagulation cascades
sbq05211  Renal cell carcinoma
KO pathway
ko04611   
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