KEGG   PATHWAY: eju04611
Entry
eju04611                    Pathway                                
Name
Platelet activation - Eumetopias jubatus (Steller sea lion)
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
eju04611  Platelet activation
eju04611

Other DBs
GO: 0030168
Organism
Eumetopias jubatus (Steller sea lion) [GN:eju]
Gene
114196466  F2RL3; proteinase-activated receptor 4 isoform X1 [KO:K04236]
114196720  ITGB3; integrin beta-3 [KO:K06493]
114197023  PTGIR; prostacyclin receptor [KO:K04263]
114197082  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
114197097  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
114197186  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
114197483  ACTB; actin, cytoplasmic 1 [KO:K05692]
114197723  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114197913  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
114197962  [KO:K04632]
114198019  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
114198742  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
114199120  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
114199360  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
114199416  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114199417  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
114200322  [KO:K12757]
114200324  MYL12B; myosin regulatory light chain 12B [KO:K12757]
114200401  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
114200595  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
114201001  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 [KO:K08627] [EC:3.4.24.87]
114201157  COL1A1; LOW QUALITY PROTEIN: collagen alpha-1(I) chain [KO:K06236]
114201653  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
114201663  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
114201670  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
114201676  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
114201677  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
114201869  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
114202059  GP6; platelet glycoprotein VI isoform X1 [KO:K06264]
114202297  P2RX1; P2X purinoceptor 1 [KO:K05215]
114202334  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
114202353  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114202535  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
114202960  [KO:K08047] [EC:4.6.1.1]
114202963  [KO:K08047] [EC:4.6.1.1]
114203023  [KO:K06481]
114203024  [KO:K06481]
114203265  [KO:K04456] [EC:2.7.11.1]
114203268  [KO:K04456] [EC:2.7.11.1]
114203512  [KO:K05704] [EC:2.7.10.2]
114203513  [KO:K05704] [EC:2.7.10.2]
114204052  [KO:K08512]
114204055  [KO:K08512]
114205617  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114205781  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.39]
114205825  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
114205853  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
114206518  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114206539  TLN2; talin-2 [KO:K06271]
114206904  GP5; platelet glycoprotein V [KO:K06260]
114206954  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114207042  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
114207615  GP9; platelet glycoprotein IX [KO:K06263]
114207665  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
114207895  RAP1A; ras-related protein Rap-1A [KO:K04353]
114207900  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
114208397  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114208569  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
114209004  P2RY12; P2Y purinoceptor 12 [KO:K04298]
114209143  P2RY1; P2Y purinoceptor 1 [KO:K04270]
114209890  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
114210086  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
114210152  FGB; fibrinogen beta chain isoform X1 [KO:K03904]
114210153  FGA; fibrinogen alpha chain [KO:K03903]
114210206  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
114210207  GUCY1A1; guanylate cyclase soluble subunit alpha-1 isoform X1 [KO:K12318] [EC:4.6.1.2]
114210308  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
114210498  [KO:K12319] [EC:4.6.1.2]
114211055  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
114211178  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
114211229  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
114211672  TBXAS1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
114212724  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
114213130  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114213301  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
114213699  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
114214409  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114214898  RAP1B; ras-related protein Rap-1b [KO:K07836]
114215280  F2; prothrombin isoform X1 [KO:K01313] [EC:3.4.21.5]
114215523  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114216053  ACTG1; actin, cytoplasmic 2 [KO:K05692]
114216074  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
114216386  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
114216392  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
114216613  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
114217304  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
114217620  F2R; proteinase-activated receptor 1 [KO:K03914]
114217911  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
114218273  TLN1; talin-1 isoform X1 [KO:K06271]
114218424  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114218476  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
114218773  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
114219084  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
114219135  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
114219726  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
114219898  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
114220234  FERMT3; fermitin family homolog 3 isoform X1 [KO:K17084]
114220426  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
114220482  RASGRP2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
114220523  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
114220766  COL1A2; collagen alpha-2(I) chain [KO:K06236]
114220792  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
114220836  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
114220924  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
114221305  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114221473  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
114222054  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
114222155  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
114222247  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114222284  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
114222402  ITGB1; integrin beta-1 [KO:K05719]
114222568  VWF; von Willebrand factor [KO:K03900]
114222866  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
114223681  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
114223815  COL3A1; collagen alpha-1(III) chain [KO:K19720]
114223891  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
114224308  [KO:K02649]
114224631  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114224927  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
114225106  RHOA; transforming protein RhoA [KO:K04513]
114225129  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
114225270  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
114225321  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
114225323  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
114225777  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
114226051  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
114226145  TBXA2R; thromboxane A2 receptor [KO:K04264]
114226659  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
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
eju00590  Arachidonic acid metabolism
eju04015  Rap1 signaling pathway
eju04020  Calcium signaling pathway
eju04151  PI3K-Akt signaling pathway
eju04610  Complement and coagulation cascades
eju05211  Renal cell carcinoma
KO pathway
ko04611   

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