KEGG   PATHWAY: fca04611
Entry
fca04611                    Pathway                                
Name
Platelet activation - Felis catus (domestic cat)
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
fca04611  Platelet activation
fca04611

Other DBs
GO: 0030168
Organism
Felis catus (domestic cat) [GN:fca]
Gene
100144392  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100271864  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101080675  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X2 [KO:K05859] [EC:3.1.4.11]
101080743  [KO:K06262]
101081027  F2RL3; proteinase-activated receptor 4 isoform X1 [KO:K04236]
101082033  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
101082104  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
101082354  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
101082574  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
101082668  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
101082828  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
101082829  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
101083342  [KO:K16342] [EC:3.1.1.4]
101083892  ARHGEF1; LOW QUALITY PROTEIN: rho guanine nucleotide exchange factor 1 [KO:K12330]
101084011  RHOA; transforming protein RhoA [KO:K04513]
101084179  GP9; platelet glycoprotein IX [KO:K06263]
101085247  [KO:K12757]
101085657  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
101085720  FYN; LOW QUALITY PROTEIN: tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
101085837  [KO:K12757]
101085880  VAMP8; vesicle-associated membrane protein 8 [KO:K08512]
101086761  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 isoform X1 [KO:K08627] [EC:3.4.24.87]
101087000  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
101087013  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
101087555  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087625  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
101087780  STIM1; stromal interaction molecule 1 isoform X2 [KO:K16059]
101087851  PRKCZ; protein kinase C zeta type isoform X3 [KO:K18952] [EC:2.7.11.13]
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101087958  MAPK3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
101087993  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101088062  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
101088157  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101088408  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
101089081  TBXA2R; thromboxane A2 receptor isoform X1 [KO:K04264]
101089236  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
101089428  COL1A2; collagen alpha-2(I) chain [KO:K06236]
101089435  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X2 [KO:K12319] [EC:4.6.1.2]
101089624  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X2 [KO:K06270]
101089679  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101089912  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
101090005  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101090237  ITGA2; integrin alpha-2 [KO:K06481]
101090457  GP5; platelet glycoprotein V [KO:K06260]
101090463  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
101090494  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X3 [KO:K04345] [EC:2.7.11.11]
101090795  P2RY1; P2Y purinoceptor 1 [KO:K04270]
101090942  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101091060  P2RX1; P2X purinoceptor 1 isoform X1 [KO:K05215]
101091097  TBXAS1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
101091211  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
101091536  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
101091618  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
101091744  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
101091892  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101092159  ITGB3; integrin beta-3 [KO:K06493]
101092216  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
101092262  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101092307  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
101092367  TLN2; talin-2 isoform X2 [KO:K06271]
101092552  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
101092557  PTGS1; prostaglandin G/H synthase 1 [KO:K00509] [EC:1.14.99.1]
101092680  FGG; fibrinogen gamma chain [KO:K03905]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101092837  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101092932  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101092934  FGA; fibrinogen alpha chain [KO:K03903]
101092961  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101093057  TLN1; talin-1 isoform X3 [KO:K06271]
101093110  RASGRP1; RAS guanyl-releasing protein 1 isoform X4 [KO:K04350]
101093286  [KO:K02649]
101093562  GP6; platelet glycoprotein VI isoform X2 [KO:K06264]
101093586  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101094044  P2RY12; P2Y purinoceptor 12 [KO:K04298]
101094148  ADCY7; adenylate cyclase type 7 isoform X2 [KO:K08047] [EC:4.6.1.1]
101094274  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101094327  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
101094450  RASGRP2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
101094501  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
101094708  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
101094805  VASP; vasodilator-stimulated phosphoprotein isoform X3 [KO:K06274]
101094942  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
101095353  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101095813  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
101095942  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101095993  RAP1B; ras-related protein Rap-1b [KO:K07836]
101096215  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
101096463  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
101096633  LYN; tyrosine-protein kinase Lyn isoform X3 [KO:K05854] [EC:2.7.10.2]
101096877  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
101096922  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
101097347  FERMT3; fermitin family homolog 3 [KO:K17084]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101097420  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
101097735  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
101098377  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
101098453  [KO:K04632]
101098507  ACTB; actin, cytoplasmic 1 [KO:K05692]
101099494  GUCY1A2; guanylate cyclase soluble subunit alpha-2 isoform X1 [KO:K12318] [EC:4.6.1.2]
101099632  FGB; fibrinogen beta chain [KO:K03904]
101099823  COL3A1; collagen alpha-1(III) chain [KO:K19720]
101100320  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
101100378  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
101100546  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101100609  PTGIR; prostacyclin receptor [KO:K04263]
101100749  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
101100861  F2R; LOW QUALITY PROTEIN: proteinase-activated receptor 1 [KO:K03914]
101100922  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101100930  ITGA2B; integrin alpha-IIb [KO:K06476]
101101135  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101101230  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101101375  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101101473  SNAP23; synaptosomal-associated protein 23 isoform X1 [KO:K08508]
102900772  [KO:K04632]
105260786  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
109492306  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
111556320  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123381200  [KO:K06262]
493760  VWF; von Willebrand factor precursor [KO:K03900]
751821  ITGB1; integrin beta-1 precursor [KO:K05719]
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
fca00590  Arachidonic acid metabolism
fca04015  Rap1 signaling pathway
fca04020  Calcium signaling pathway
fca04151  PI3K-Akt signaling pathway
fca04610  Complement and coagulation cascades
fca05211  Renal cell carcinoma
KO pathway
ko04611   

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