KEGG   PATHWAY: mdt04611
Entry
mdt04611                    Pathway                                
Name
Platelet activation - Myotis daubentonii (Daubenton's bat)
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
mdt04611  Platelet activation
mdt04611

Other DBs
GO: 0030168
Organism
Myotis daubentonii (Daubenton's bat) [GN:mdt]
Gene
132211119  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
132211234  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
132211786  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
132212019  [KO:K04634]
132212126  TLN1; talin-1 isoform X1 [KO:K06271]
132212302  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
132212526  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 isoform X1 [KO:K08627] [EC:3.4.24.87]
132212742  [KO:K06269] [EC:3.1.3.16]
132213143  VAMP8; vesicle-associated membrane protein 8 [KO:K08512]
132213506  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
132213586  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
132213639  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.39]
132214332  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
132214958  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
132215517  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132215779  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
132215835  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
132215861  RHOA; transforming protein RhoA [KO:K04513]
132216059  [KO:K04513]
132216502  GP6; LOW QUALITY PROTEIN: platelet glycoprotein VI [KO:K06264]
132216683  PTGIR; prostacyclin receptor [KO:K04263]
132216690  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
132216730  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
132216811  ARHGEF1; rho guanine nucleotide exchange factor 1 [KO:K12330]
132216889  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
132217215  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
132217308  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
132217592  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
132217627  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
132218021  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
132218022  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
132218145  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
132218200  P2RX1; P2X purinoceptor 1 isoform X1 [KO:K05215]
132218548  ITGB3; integrin beta-3 [KO:K06493]
132218615  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
132218743  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
132218840  COL1A1; collagen alpha-1(I) chain [KO:K06236]
132219202  ACTG1; actin, cytoplasmic 2 [KO:K05692]
132219755  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
132219953  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
132220181  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
132220296  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
132220440  [KO:K06472]
132220508  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
132220747  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
132220908  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
132221703  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
132221924  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
132222107  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
132222289  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
132222407  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
132223978  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
132225178  [KO:K07836]
132226592  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
132226690  [KO:K12319] [EC:4.6.1.2]
132226843  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
132226858  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
132227175  VWF; von Willebrand factor [KO:K03900]
132227391  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
132227516  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
132227892  RAP1B; ras-related protein Rap-1b isoform X1 [KO:K07836]
132228358  [KO:K00907] [EC:2.7.11.18]
132228444  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
132230026  P2RY1; P2Y purinoceptor 1 [KO:K04270]
132230097  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
132230128  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132230250  GP5; platelet glycoprotein V [KO:K06260]
132230328  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
132230329  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
132230525  P2RY12; P2Y purinoceptor 12 [KO:K04298]
132230648  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
132230901  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
132231240  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
132231710  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132231774  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
132232782  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
132233026  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
132233511  F2R; proteinase-activated receptor 1 isoform X1 [KO:K03914]
132233575  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
132233655  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
132233791  ITGA2; integrin alpha-2 [KO:K06481]
132234607  [KO:K04456] [EC:2.7.11.1]
132234815  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
132234863  F2RL3; proteinase-activated receptor 4 [KO:K04236]
132234959  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
132235200  TBXA2R; thromboxane A2 receptor [KO:K04264]
132235403  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
132235404  GUCY1B1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
132235448  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
132235449  FGB; fibrinogen beta chain [KO:K03904]
132235951  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
132236028  ACTB; actin, cytoplasmic 1 [KO:K05692]
132236077  TLN2; talin-2 isoform X1 [KO:K06271]
132236135  FGA; fibrinogen alpha chain [KO:K03903]
132236985  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
132237408  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
132237411  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
132237456  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
132238037  COL3A1; collagen alpha-1(III) chain [KO:K19720]
132238532  SNAP23; synaptosomal-associated protein 23 isoform X1 [KO:K08508]
132238642  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
132238656  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
132239051  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
132239164  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
132239194  [KO:K04632]
132239196  [KO:K04632]
132239361  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
132239363  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
132239493  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
132239597  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
132239734  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
132239766  [KO:K12757]
132239767  [KO:K12757]
132240130  [KO:K04632]
132240229  GP9; platelet glycoprotein IX [KO:K06263]
132240447  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
132240582  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
132240692  [KO:K04513]
132240856  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
132241024  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
132241215  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
132241338  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
132241461  RASGRP2; RAS guanyl-releasing protein 2 [KO:K12361]
132241471  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
132241472  FERMT3; fermitin family homolog 3 [KO:K17084]
132242619  NOS3; nitric oxide synthase 3 isoform X1 [KO:K13242] [EC:1.14.13.39]
132242828  TBXAS1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
132242951  COL1A2; collagen alpha-2(I) chain [KO:K06236]
132243106  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
132243125  ITGB1; integrin beta-1 isoform X1 [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
  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
mdt00590  Arachidonic acid metabolism
mdt04015  Rap1 signaling pathway
mdt04020  Calcium signaling pathway
mdt04151  PI3K-Akt signaling pathway
mdt04610  Complement and coagulation cascades
mdt05211  Renal cell carcinoma
KO pathway
ko04611   

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