KEGG   PATHWAY: mcc04611
Entry
mcc04611                    Pathway                                
Name
Platelet activation - Macaca mulatta (rhesus 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
mcc04611  Platelet activation
mcc04611

Other DBs
GO: 0030168
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
721732  TBXA2R; thromboxane A2 receptor [KO:K04264]
712729  F2; prothrombin precursor [KO:K01313] [EC:3.4.21.5]
707370  F2R; proteinase-activated receptor 1 [KO:K03914]
718843  F2RL3; proteinase-activated receptor 4 [KO:K04236]
718144  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
722198  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X2 [KO:K12330]
712096  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X2 [KO:K07532]
706455  RHOA; transforming protein RhoA [KO:K04513]
698223  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
708444  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
703302  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
709935  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
721735  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
695735  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
694957  MYL12B; myosin regulatory light chain 12B [KO:K12757]
695077  MYL12A; myosin, light chain 12A, regulatory, non-sarcomeric isoform X1 [KO:K12757]
707658  P2RX1; P2X purinoceptor 1 [KO:K05215]
700190  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
703669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
708714  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
718040  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
717963  STIM1; stromal interaction molecule 1 precursor [KO:K16059]
712830  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
707361  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
715422  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
716132  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
708507  P2RY1; P2Y purinoceptor 1 [KO:K04270]
705680  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
701951  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
718418  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
718387  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
717764  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
710340  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
574352  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
703838  RASGRP1; RAS guanyl-releasing protein 1 isoform X3 [KO:K04350]
722044  RASGRP2; RAS guanyl-releasing protein 2 [KO:K12361]
704404  RAP1A; ras-related protein Rap-1A [KO:K04353]
718171  RAP1B; ras-related protein Rap-1b [KO:K07836]
693750  LOW QUALITY PROTEIN: ras-related protein Rap-1b [KO:K07836]
707383  amyloid beta A4 precursor protein-binding family B member 1-interacting protein isoform X1 [KO:K17704]
705008  TLN2; talin-2 isoform X1 [KO:K06271]
696298  TLN1; talin-1 isoform X1 [KO:K06271]
714955  ITGA2B; integrin alpha-IIb isoform X2 [KO:K06476]
717379  ITGB3; integrin beta-3 [KO:K06493]
722120  FERMT3; fermitin family homolog 3 [KO:K17084]
698244  FGA; fibrinogen alpha chain isoform X1 [KO:K03903]
698487  FGB; fibrinogen beta chain [KO:K03904]
698363  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
710036  P2RY12; P2Y purinoceptor 12 [KO:K04298]
699310  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
703780  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
708940  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
697230  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
695328  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
693523  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
714684  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
715897  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
707978  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
694730  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
695792  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
706789  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
716546  PTGIR; prostacyclin receptor [KO:K04263]
694289  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
100424899  neuroendocrine secretory protein 55 [KO:K04632]
698857  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
722027  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
722023  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
709728  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
718632  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
700652  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
716022  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
713687  ACTG1; actin, cytoplasmic 2 [KO:K05692]
574285  ACTB; actin, cytoplasmic 1 [KO:K05692]
705671  actin, cytoplasmic 2-like [KO:K05692]
701057  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
716936  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
719996  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a precursor [KO:K06472]
704102  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
574201  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
700359  COL1A2; collagen alpha-2(I) chain precursor [KO:K06236]
574131  COL3A1; collagen alpha-1(III) chain precursor [KO:K19720]
100424512  GP6; platelet glycoprotein VI isoform X1 [KO:K06264]
106994860  LOW QUALITY PROTEIN: platelet glycoprotein VI [KO:K06264]
720291  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma precursor [KO:K07983]
698553  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
574214  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
703572  ITGA2; integrin alpha-2 precursor [KO:K06481]
574312  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
716098  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
709959  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
710552  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
707310  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
719367  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
698996  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
700374  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
714173  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
703000  BTK; tyrosine-protein kinase BTK isoform X2 [KO:K07370] [EC:2.7.10.2]
722019  VWF; von Willebrand factor precursor [KO:K03900]
707776  GP5; platelet glycoprotein V [KO:K06260]
721584  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
712129  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
704202  GP9; platelet glycoprotein IX precursor [KO:K06263]
714717  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
697747  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
700591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
714231  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
699365  GUCY1A1; guanylate cyclase soluble subunit alpha-1 isoform X2 [KO:K12318] [EC:4.6.1.2]
706615  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
100424944  GUCY1B1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
114673584  LOW QUALITY PROTEIN: guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
703356  PRKG1; cGMP-dependent protein kinase 1 isoform X2 [KO:K07376] [EC:2.7.11.12]
696308  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
715745  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
715794  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
718976  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
719085  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
716635  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
100533113  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
718510  cytosolic phospholipase A2 gamma isoform X3 [KO:K16342] [EC:3.1.1.4]
707592  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
707690  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
100424593  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
698213  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
711748  TBXAS1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
708225  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
695851  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
  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
mcc00590  Arachidonic acid metabolism
mcc04015  Rap1 signaling pathway
mcc04020  Calcium signaling pathway
mcc04151  PI3K-Akt signaling pathway
mcc04610  Complement and coagulation cascades
mcc05211  Renal cell carcinoma
KO pathway
ko04611   
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