KEGG   PATHWAY: aml04611
Entry
aml04611                    Pathway                                
Name
Platelet activation - Ailuropoda melanoleuca (giant panda)
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
aml04611  Platelet activation
aml04611

Other DBs
GO: 0030168
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100463691  P2RX1; P2X purinoceptor 1 isoform X1 [KO:K05215]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100463836  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
100464499  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100464853  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100465223  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100465232  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100465476  MAPK14; mitogen-activated protein kinase 14 isoform X3 [KO:K04441] [EC:2.7.11.24]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100466003  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
100466132  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100466140  FGB; fibrinogen beta chain [KO:K03904]
100466231  FERMT3; fermitin family homolog 3 [KO:K17084]
100466387  FGG; fibrinogen gamma chain isoform X2 [KO:K03905]
100466408  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100466965  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100467120  [KO:K06261]
100467161  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
100467892  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100467982  P2RY12; P2Y purinoceptor 12 [KO:K04298]
100468070  [KO:K12319] [EC:4.6.1.2]
100468252  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100468670  GP1BB; LOW QUALITY PROTEIN: platelet glycoprotein Ib beta chain [KO:K06262]
100468710  VWF; von Willebrand factor [KO:K03900]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100469231  [KO:K04632]
100469244  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
100469401  FGA; fibrinogen alpha chain [KO:K03903]
100469491  P2RY1; P2Y purinoceptor 1 [KO:K04270]
100469628  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100469728  F2RL3; proteinase-activated receptor 4 isoform X1 [KO:K04236]
100469758  GP5; platelet glycoprotein V [KO:K06260]
100469891  TLN2; talin-2 [KO:K06271]
100469987  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100470240  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
100470322  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X2 [KO:K21289] [EC:2.7.1.153]
100470490  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
100470620  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
100470931  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
100470998  [KO:K16342] [EC:3.1.1.4]
100471078  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
100471142  [KO:K12757]
100471164  ADCY3; adenylate cyclase type 3 isoform X2 [KO:K08043] [EC:4.6.1.1]
100471456  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100471747  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100471767  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100471801  RAP1A; ras-related protein Rap-1A [KO:K04353]
100471856  TLN1; talin-1 [KO:K06271]
100471873  PTGIR; prostacyclin receptor [KO:K04263]
100471940  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100472299  [KO:K12757]
100472303  BTK; tyrosine-protein kinase BTK isoform X3 [KO:K07370] [EC:2.7.10.2]
100472350  COL3A1; collagen alpha-1(III) chain [KO:K19720]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100472777  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100472871  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
100473195  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100473453  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
100473680  [KO:K04632]
100474121  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100474254  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
100474271  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
100474469  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
100474482  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
100474543  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
100474779  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100474885  COL1A2; collagen alpha-2(I) chain [KO:K06236]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100476029  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100476237  COL1A1; collagen alpha-1(I) chain [KO:K06236]
100476256  ITGB3; integrin beta-3 [KO:K06493]
100476403  ITGA2; integrin alpha-2 [KO:K06481]
100476487  TBXA2R; thromboxane A2 receptor [KO:K04264]
100476495  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100476667  GP6; platelet glycoprotein VI [KO:K06264]
100476723  RHOA; transforming protein RhoA [KO:K04513]
100476899  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
100476922  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100477067  PIK3R5; LOW QUALITY PROTEIN: phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
100477081  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
100477324  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
100477378  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
100477778  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
100477838  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
100477888  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100478425  VAMP8; vesicle-associated membrane protein 8 [KO:K08512]
100478770  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100479606  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
100480235  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100480240  RAP1B; ras-related protein Rap-1b [KO:K07836]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100480483  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100480603  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
100481099  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 [KO:K08627] [EC:3.4.24.87]
100481235  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
100481263  MYLK; myosin light chain kinase, smooth muscle isoform X5 [KO:K00907] [EC:2.7.11.18]
100481364  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X2 [KO:K12319] [EC:4.6.1.2]
100481505  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
100481563  TBXAS1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
100481755  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100481961  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
100481994  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
100482519  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100482557  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
100482619  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
100482697  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100483012  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
100483617  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100483990  NOS3; nitric oxide synthase, endothelial isoform X2 [KO:K13242] [EC:1.14.13.39]
100483995  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
100484002  GP9; platelet glycoprotein IX [KO:K06263]
100484185  ITGA2B; integrin alpha-IIb [KO:K06476]
100484889  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
100484933  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105234638  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
105236463  RASGRP2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
105240499  F2R; proteinase-activated receptor 1 [KO:K03914]
117799888  [KO:K12757]
117800125  [KO:K05692]
117800181  [KO:K05692]
117800361  [KO:K05692]
117800408  [KO:K05692]
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
aml00590  Arachidonic acid metabolism
aml04015  Rap1 signaling pathway
aml04020  Calcium signaling pathway
aml04151  PI3K-Akt signaling pathway
aml04610  Complement and coagulation cascades
aml05211  Renal cell carcinoma
KO pathway
ko04611   

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