KEGG   PATHWAY: bta04611
Entry
bta04611                    Pathway                                
Name
Platelet activation - Bos taurus (cow)
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
bta04611  Platelet activation
bta04611

Other DBs
GO: 0030168
Organism
Bos taurus (cow) [GN:bta]
Gene
538783  TBXA2R; thromboxane A2 receptor [KO:K04264]
280685  F2; prothrombin precursor [KO:K01313] [EC:3.4.21.5]
526585  F2R; proteinase-activated receptor 1 precursor [KO:K03914]
538963  F2RL3; proteinase-activated receptor 4 precursor [KO:K04236]
505611  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
513377  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
503575  ARHGEF12; rho guanine nucleotide exchange factor 12 [KO:K07532]
338049  RHOA; transforming protein RhoA [KO:K04513]
785911  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
282041  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
282318  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
516175  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
538829  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
538606  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
531505  MYL12A; myosin regulatory light polypeptide 9 [KO:K12757]
614055  MYL12B; myosin regulatory light chain 12B [KO:K12757]
514898  P2RX1; P2X purinoceptor 1 [KO:K05215]
517688  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
317697  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
281878  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
281879  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
534816  STIM1; stromal interaction molecule 1 precursor [KO:K16059]
338037  MYLK; myosin light chain kinase, smooth muscle isoform 1 [KO:K00907] [EC:2.7.11.18]
533378  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
526379  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
518025  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
281963  P2RY1; P2Y purinoceptor 1 [KO:K04270]
536654  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
287026  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
281985  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
515669  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
508888  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
286877  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
528478  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
533125  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
512056  RASGRP2; RAS guanyl-releasing protein 2 [KO:K12361]
282031  RAP1A; ras-related protein Rap-1A [KO:K04353]
327708  RAP1B; ras-related protein Rap-1b [KO:K07836]
789148  ras-related protein Rap-1b [KO:K07836]
533670  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
783470  TLN1; talin-1 [KO:K06271]
528252  TLN2; talin-2 isoform X1 [KO:K06271]
515011  ITGA2B; integrin alpha-IIb [KO:K06476]
282642  ITGB3; integrin beta-3 precursor [KO:K06493]
525159  FERMT3; fermitin family homolog 3 [KO:K17084]
522039  FGA; fibrinogen alpha chain precursor [KO:K03903]
510522  FGB; fibrinogen beta chain precursor [KO:K03904]
280792  FGG; fibrinogen gamma-B chain precursor [KO:K03905]
408007  P2RY12; P2Y purinoceptor 12 [KO:K04298]
281790  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
281791  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
539521  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
281601  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
510708  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
535603  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
788151  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
505740  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
509936  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
281603  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
535017  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
525482  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
520278  PTGIR; prostacyclin receptor [KO:K04263]
281793  GNAS; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
530001  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
614838  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X3 [KO:K21290]
515621  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
282322  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
282323  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
514902  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
404122  ACTG1; actin, cytoplasmic 2 [KO:K05692]
280979  ACTB; actin, cytoplasmic 1 [KO:K05692]
535742  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
540310  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
782652  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a [KO:K06472]
515515  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
282188  COL1A2; collagen alpha-2(I) chain precursor [KO:K06236]
282187  COL1A1; collagen alpha-1(I) chain precursor [KO:K06236]
510833  COL3A1; collagen alpha-1(III) chain precursor [KO:K19720]
100336616  GP6; platelet glycoprotein VI [KO:K06264]
282226  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma precursor [KO:K07983]
534996  LYN; tyrosine-protein kinase Lyn [KO:K05854] [EC:2.7.10.2]
527263  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
281872  ITGA2; integrin alpha-2 precursor [KO:K06481]
281876  ITGB1; integrin beta-1 precursor [KO:K05719]
282306  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
517948  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
504531  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
282308  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
286865  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
282307  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
513244  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
100337091  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
533459  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
280958  VWF; von Willebrand factor precursor [KO:K03900]
522692  GP5; platelet glycoprotein V [KO:K06260]
504977  GP1BA; LOW QUALITY PROTEIN: platelet glycoprotein Ib alpha chain [KO:K06261]
617668  GP9; platelet glycoprotein IX [KO:K06263]
534923  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
280991  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100137872  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
287024  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
613600  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
281216  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
282433  GUCY1B1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
112449027  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
282004  PRKG1; cGMP-dependent protein kinase 1 [KO:K07376] [EC:2.7.11.12]
533330  PRKG2; cGMP-dependent protein kinase 2 [KO:K19477] [EC:2.7.11.12]
534492  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
535327  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
512943  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
618906  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
327672  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
531391  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
526364  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
505485  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
522866  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
531209  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
525072  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
282022  PTGS1; prostaglandin G/H synthase 1 precursor [KO:K00509] [EC:1.14.99.1]
509326  TBXAS1; thromboxane-A synthase [KO:K01832] [EC:5.3.99.5]
522423  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
507309  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
bta00590  Arachidonic acid metabolism
bta04015  Rap1 signaling pathway
bta04020  Calcium signaling pathway
bta04151  PI3K-Akt signaling pathway
bta04610  Complement and coagulation cascades
bta05211  Renal cell carcinoma
KO pathway
ko04611   
LinkDB

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