KEGG   PATHWAY: tge04611
Entry
tge04611                    Pathway                                
Name
Platelet activation - Theropithecus gelada (gelada)
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
tge04611  Platelet activation
tge04611

Other DBs
GO: 0030168
Organism
Theropithecus gelada (gelada) [GN:tge]
Gene
112604540  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
112604670  [KO:K06269] [EC:3.1.3.16]
112604719  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
112604937  [KO:K12757]
112605108  VAMP8; vesicle-associated membrane protein 8 [KO:K08512]
112605588  FERMT3; fermitin family homolog 3 [KO:K17084]
112606072  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
112606262  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
112606320  F2; prothrombin isoform X1 [KO:K01313] [EC:3.4.21.5]
112606675  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
112606964  RASGRP2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
112606994  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
112607332  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
112607583  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 isoform X1 [KO:K08627] [EC:3.4.24.87]
112607858  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
112608183  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
112608309  TLN1; talin-1 isoform X1 [KO:K06271]
112608311  RHOC; rho-related GTP-binding protein RhoC isoform X1 [KO:K04513]
112608327  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
112608352  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
112609015  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
112609162  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
112609286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112609387  ITGA2B; integrin alpha-IIb [KO:K06476]
112609477  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
112609513  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
112609527  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
112609630  P2RX1; P2X purinoceptor 1 [KO:K05215]
112609651  ACTG1; actin, cytoplasmic 2 isoform X1 [KO:K05692]
112609752  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
112609798  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
112610985  [KO:K12319] [EC:4.6.1.2]
112611351  [KO:K05692]
112611393  [KO:K12757]
112611395  MYL12B; myosin regulatory light chain 12B [KO:K12757]
112611421  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
112611901  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
112612001  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
112612103  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
112612165  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
112612288  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112612368  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
112612422  PTGIR; prostacyclin receptor [KO:K04263]
112612552  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
112612936  GP6; platelet glycoprotein VI [KO:K06264]
112612978  TBXA2R; thromboxane A2 receptor [KO:K04264]
112613300  F2RL3; proteinase-activated receptor 4 [KO:K04236]
112613998  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
112614034  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
112614214  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
112614273  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
112614388  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
112614522  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
112614524  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
112615467  BTK; tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
112617420  [KO:K18952] [EC:2.7.11.13]
112617717  [KO:K05692]
112618470  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
112618524  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
112618614  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
112618796  P2RY12; P2Y purinoceptor 12 [KO:K04298]
112618864  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
112618874  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112618989  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
112619046  P2RY1; P2Y purinoceptor 1 [KO:K04270]
112619273  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
112619294  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112619375  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
112619568  GP9; platelet glycoprotein IX [KO:K06263]
112619623  GP5; platelet glycoprotein V [KO:K06260]
112620281  COL1A2; collagen alpha-2(I) chain isoform X1 [KO:K06236]
112620359  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
112620857  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
112620903  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
112620936  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
112621111  TBXAS1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
112622050  [KO:K04513]
112622236  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
112622701  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
112622714  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
112622816  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
112622840  [KO:K12757]
112623401  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
112623522  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
112624826  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
112624899  FGA; fibrinogen alpha chain isoform X1 [KO:K03903]
112624900  FGB; fibrinogen beta chain isoform X1 [KO:K03904]
112624924  GUCY1A1; guanylate cyclase soluble subunit alpha-1 isoform X1 [KO:K12318] [EC:4.6.1.2]
112624957  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
112625333  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
112625820  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
112625914  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112625956  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112626009  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
112626061  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
112626605  F2R; proteinase-activated receptor 1 isoform X1 [KO:K03914]
112627002  ITGA2; integrin alpha-2 [KO:K06481]
112627440  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
112627584  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
112627599  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
112627618  TLN2; talin-2 [KO:K06271]
112627837  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
112627871  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
112627983  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
112628083  SNAP23; synaptosomal-associated protein 23 isoform X1 [KO:K08508]
112629473  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112629482  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
112629924  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma isoform X1 [KO:K07983]
112630297  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
112630332  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
112631135  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
112631395  ITGB1; integrin beta-1 [KO:K05719]
112631997  [KO:K17704]
112632629  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
112632630  [KO:K04632]
112632792  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
112632915  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
112633066  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
112633067  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
112633206  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
112633275  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
112633533  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
112633654  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
112633984  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
112634042  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112634287  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
112634325  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
112634393  VWF; von Willebrand factor [KO:K03900]
112634518  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
112634597  ORAI1; calcium release-activated calcium channel protein 1 isoform X1 [KO:K16056]
112635149  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
112635460  RAP1B; ras-related protein Rap-1b isoform X1 [KO:K07836]
112636105  COL3A1; collagen alpha-1(III) chain [KO:K19720]
112636950  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
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
tge00590  Arachidonic acid metabolism
tge04015  Rap1 signaling pathway
tge04020  Calcium signaling pathway
tge04151  PI3K-Akt signaling pathway
tge04610  Complement and coagulation cascades
tge05211  Renal cell carcinoma
KO pathway
ko04611   

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