KEGG   PATHWAY: rro04611
Entry
rro04611                    Pathway                                
Name
Platelet activation - Rhinopithecus roxellana (golden snub-nosed 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
rro04611  Platelet activation
rro04611

Other DBs
GO: 0030168
Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104653559  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
104653717  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
104654121  MYL12A; myosin regulatory light chain 12A isoform X2 [KO:K12757]
104654122  MYL12B; myosin regulatory light chain 12B [KO:K12757]
104654186  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104654717  ITGA2B; integrin alpha-IIb [KO:K06476]
104654813  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
104654871  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
104654953  ACTG1; actin, cytoplasmic 2 [KO:K05692]
104655275  GP9; platelet glycoprotein IX isoform X1 [KO:K06263]
104655407  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
104655430  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
104655463  ROCK1; LOW QUALITY PROTEIN: rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
104655485  F2R; proteinase-activated receptor 1 [KO:K03914]
104655777  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104655840  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
104655861  PTGS1; prostaglandin G/H synthase 1 isoform X2 [KO:K00509] [EC:1.14.99.1]
104655958  GUCY1A2; guanylate cyclase soluble subunit alpha-2 isoform X1 [KO:K12318] [EC:4.6.1.2]
104655987  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
104656601  TBXAS1; thromboxane-A synthase isoform X2 [KO:K01832] [EC:5.3.99.5]
104656682  GP1BB; platelet glycoprotein Ib beta chain isoform X2 [KO:K06262]
104657125  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
104657126  FGA; fibrinogen alpha chain [KO:K03903]
104657127  FGB; fibrinogen beta chain [KO:K03904]
104657228  ARHGEF12; LOW QUALITY PROTEIN: rho guanine nucleotide exchange factor 12 [KO:K07532]
104657250  [KO:K05692]
104658100  GUCY1A1; guanylate cyclase soluble subunit alpha-1 isoform X1 [KO:K12318] [EC:4.6.1.2]
104658102  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
104658283  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
104658296  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
104658457  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
104658672  RAP1B; ras-related protein Rap-1b [KO:K07836]
104658932  RAP1A; ras-related protein Rap-1A [KO:K04353]
104658948  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104659174  [KO:K05692]
104659579  BTK; tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
104659669  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
104659684  RASGRP1; RAS guanyl-releasing protein 1 isoform X2 [KO:K04350]
104660767  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
104660769  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104660989  F2RL3; proteinase-activated receptor 4 isoform X1 [KO:K04236]
104661051  [KO:K04345] [EC:2.7.11.11]
104661238  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
104661780  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
104662008  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
104662061  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
104662124  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104662513  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
104662674  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
104662724  [KO:K12319] [EC:4.6.1.2]
104663050  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104663082  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
104663301  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
104663314  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
104663606  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
104663797  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
104663799  [KO:K04632]
104664252  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
104664371  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
104664823  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
104665061  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104665173  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
104665228  ACTB; actin, cytoplasmic 1 [KO:K05692]
104665260  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
104665267  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
104665342  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
104665441  TBXA2R; thromboxane A2 receptor [KO:K04264]
104666279  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
104666910  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
104666913  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
104666914  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
104667102  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
104667372  RHOA; transforming protein RhoA [KO:K04513]
104667744  COL3A1; collagen alpha-1(III) chain [KO:K19720]
104667982  P2RY12; P2Y purinoceptor 12 [KO:K04298]
104668142  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
104668296  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
104668398  F2; prothrombin isoform X1 [KO:K01313] [EC:3.4.21.5]
104668466  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
104668854  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
104669185  P2RY1; P2Y purinoceptor 1 [KO:K04270]
104669518  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
104669720  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 [KO:K08627] [EC:3.4.24.87]
104669878  GP5; platelet glycoprotein V isoform X1 [KO:K06260]
104670605  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104670864  TLN2; talin-2 isoform X1 [KO:K06271]
104671165  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
104671216  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
104671624  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
104672288  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
104672428  TLN1; talin-1 [KO:K06271]
104672477  ITGA2; integrin alpha-2 [KO:K06481]
104672569  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
104672769  [KO:K05692]
104673017  FERMT3; fermitin family homolog 3 [KO:K17084]
104673041  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104673127  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
104673274  RASGRP2; RAS guanyl-releasing protein 2 isoform X3 [KO:K12361]
104673307  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
104673397  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
104673405  PTGIR; prostacyclin receptor [KO:K04263]
104673438  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
104673480  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
104674083  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
104674752  GP6; platelet glycoprotein VI [KO:K06264]
104675136  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
104675191  ROCK2; rho-associated protein kinase 2 isoform X5 [KO:K17388] [EC:2.7.11.39]
104675331  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104675393  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
104675436  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
104675620  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104675683  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
104675773  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
104676067  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
104676121  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104676729  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
104676897  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104677048  VAMP8; vesicle-associated membrane protein 8 [KO:K08512]
104677227  P2RX1; P2X purinoceptor 1 [KO:K05215]
104677402  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
104677489  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
104679643  [KO:K17704]
104680130  VWF; LOW QUALITY PROTEIN: von Willebrand factor [KO:K03900]
104680270  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
104680672  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104681150  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104681871  [KO:K05692]
104682783  COL1A2; collagen alpha-2(I) chain [KO:K06236]
104682867  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
104682868  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
115893905  [KO:K04456] [EC:2.7.11.1]
115895854  [KO:K05704] [EC:2.7.10.2]
115897634  [KO:K16342] [EC:3.1.1.4]
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
rro00590  Arachidonic acid metabolism
rro04015  Rap1 signaling pathway
rro04020  Calcium signaling pathway
rro04151  PI3K-Akt signaling pathway
rro04610  Complement and coagulation cascades
rro05211  Renal cell carcinoma
KO pathway
ko04611   

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