KEGG   PATHWAY: shr04611
Entry
shr04611                    Pathway                                
Name
Platelet activation - Sarcophilus harrisii (Tasmanian devil)
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
shr04611  Platelet activation
shr04611

Other DBs
GO: 0030168
Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100913262  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100913437  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
100913647  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100913731  [KO:K04345] [EC:2.7.11.11]
100913854  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
100913968  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100914094  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
100914602  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
100914706  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100915092  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
100915116  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100915158  P2RY12; P2Y purinoceptor 12 [KO:K04298]
100915186  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
100915481  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100915832  F2RL3; proteinase-activated receptor 4 [KO:K04236]
100916041  COL1A2; collagen alpha-2(I) chain [KO:K06236]
100916115  [KO:K06264]
100916150  RASGRP2; RAS guanyl-releasing protein 2 [KO:K12361]
100916183  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100916377  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
100916611  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
100916712  [KO:K05692]
100916740  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
100916865  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
100916996  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
100917893  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
100917987  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100918090  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
100918117  P2RY1; P2Y purinoceptor 1 [KO:K04270]
100918158  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
100918532  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X7 [KO:K04958]
100918784  TBXA2R; thromboxane A2 receptor [KO:K04264]
100918934  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
100919051  ACTB; actin, cytoplasmic 1 [KO:K05692]
100919206  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X2 [KO:K05859] [EC:3.1.4.11]
100919651  [KO:K12757]
100920097  [KO:K12757]
100920135  RAP1B; ras-related protein Rap-1b [KO:K07836]
100920243  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100920485  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
100920526  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
100920734  ITGB3; integrin beta-3 [KO:K06493]
100921270  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100921649  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
100921931  RHOA; transforming protein RhoA [KO:K04513]
100922193  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100922434  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100922938  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100923088  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
100923264  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
100923297  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
100923807  [KO:K05692]
100923926  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100924667  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
100924870  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 [KO:K08627] [EC:3.4.24.87]
100924976  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100925013  MAPK14; mitogen-activated protein kinase 14 isoform X2 [KO:K04441] [EC:2.7.11.24]
100925131  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
100925440  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100925447  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100925455  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
100925605  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
100925657  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100926025  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
100926039  [KO:K06264]
100926529  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
100926892  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100926931  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
100927005  PLA2G4C; cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
100927268  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
100927283  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
100928302  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100928323  TLN2; talin-2 [KO:K06271]
100928661  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
100928725  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100928729  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
100928746  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
100928990  MAPK11; LOW QUALITY PROTEIN: mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100929015  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100929183  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
100929196  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
100929278  ADCY7; adenylate cyclase type 7 isoform X3 [KO:K08047] [EC:4.6.1.1]
100929308  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
100929360  [KO:K04345] [EC:2.7.11.11]
100929683  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
100929811  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100929947  FGA; fibrinogen alpha chain [KO:K03903]
100930068  GP9; platelet glycoprotein IX isoform X1 [KO:K06263]
100930207  FGB; fibrinogen beta chain [KO:K03904]
100930256  COL3A1; collagen alpha-1(III) chain [KO:K19720]
100930570  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100930666  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
100931238  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
100931427  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X2 [KO:K12319] [EC:4.6.1.2]
100931658  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
100932021  ITGA2B; integrin alpha-IIb [KO:K06476]
100932099  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100932191  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
100932257  [KO:K12319] [EC:4.6.1.2]
100932634  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100932859  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
100933116  TLN1; talin-1 [KO:K06271]
100933239  TBXAS1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
100933673  VWF; von Willebrand factor [KO:K03900]
100934049  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100934183  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
100934311  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100934757  F2R; proteinase-activated receptor 1 [KO:K03914]
100935037  ARHGAP35; LOW QUALITY PROTEIN: rho GTPase-activating protein 35 [KO:K05732]
100935230  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100935384  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
100935403  RAP1A; ras-related protein Rap-1A isoform X2 [KO:K04353]
105749727  ITGA2; integrin alpha-2 [KO:K06481]
105749979  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105750075  ARHGEF1; LOW QUALITY PROTEIN: rho guanine nucleotide exchange factor 1 [KO:K12330]
105750216  [KO:K06264]
105750980  FERMT3; fermitin family homolog 3 [KO:K17084]
111719559  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
111720189  PTGIR; prostacyclin receptor [KO:K04263]
111720256  [KO:K06264]
116420869  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
116421250  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
shr00590  Arachidonic acid metabolism
shr04015  Rap1 signaling pathway
shr04020  Calcium signaling pathway
shr04151  PI3K-Akt signaling pathway
shr04610  Complement and coagulation cascades
shr05211  Renal cell carcinoma
KO pathway
ko04611   

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