KEGG   PATHWAY: lve04611
Entry
lve04611                    Pathway                                
Name
Platelet activation - Lipotes vexillifer (Yangtze River dolphin)
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
lve04611  Platelet activation
lve04611

Other DBs
GO: 0030168
Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103068503  [KO:K03905]
103068674  GP6; platelet glycoprotein VI [KO:K06264]
103068778  FGA; fibrinogen alpha chain [KO:K03903]
103068921  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103069063  FGB; fibrinogen beta chain isoform X1 [KO:K03904]
103069188  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
103069239  RAP1A; ras-related protein Rap-1A [KO:K04353]
103069249  [KO:K06236]
103069455  PIK3CG; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
103069938  GUCY1A2; guanylate cyclase soluble subunit alpha-2-like [KO:K12318] [EC:4.6.1.2]
103069979  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
103070077  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
103070260  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103070292  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
103070370  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103070387  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103070451  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103070821  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
103070997  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
103071564  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
103071605  GP9; platelet glycoprotein IX [KO:K06263]
103071829  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
103071917  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
103071951  F2RL3; proteinase-activated receptor 4 [KO:K04236]
103071971  [KO:K06236]
103071997  PPP1R12A; protein phosphatase 1 regulatory subunit 12A-like isoform X1 [KO:K06270]
103072342  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
103072994  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
103073004  VWF; von Willebrand factor [KO:K03900]
103073514  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
103074112  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
103074204  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 [KO:K08627] [EC:3.4.24.87]
103074387  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
103074440  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
103074732  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
103075104  COL3A1; collagen alpha-1(III) chain-like [KO:K19720]
103075153  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
103075302  [KO:K12318] [EC:4.6.1.2]
103075329  [KO:K04270]
103075356  ITGA2B; integrin alpha-IIb [KO:K06476]
103075499  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
103075543  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103075554  P2RX1; P2X purinoceptor 1 [KO:K05215]
103075578  GUCY1B3; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
103076182  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103076365  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103076642  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
103076764  TBXAS1; thromboxane-A synthase [KO:K01832] [EC:5.3.99.5]
103076917  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
103077223  ACTB; actin, cytoplasmic 1 [KO:K05692]
103077308  GNAI2; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
103077464  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103077489  [KO:K08508]
103077530  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103077707  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
103077800  GP5; platelet glycoprotein V [KO:K06260]
103078013  F2R; proteinase-activated receptor 1 [KO:K03914]
103078049  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103078201  RASGRP2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
103078639  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103078677  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103078697  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103078710  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103078725  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103079287  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103079294  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
103079539  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
103079796  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
103079981  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
103080185  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
103080471  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
103080961  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
103081367  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
103081507  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
103081517  TBXA2R; thromboxane A2 receptor [KO:K04264]
103081539  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103082406  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
103082420  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103082455  [KO:K04514] [EC:2.7.11.39]
103083209  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103083395  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein-like [KO:K17704]
103083426  RAP1B; ras-related protein Rap-1b isoform X1 [KO:K07836]
103083510  PLA2G4D; LOW QUALITY PROTEIN: cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
103083551  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
103083784  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
103083833  ARHGEF12; LOW QUALITY PROTEIN: rho guanine nucleotide exchange factor 12 [KO:K07532]
103083884  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
103083960  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103084078  P2RY12; LOW QUALITY PROTEIN: P2Y purinoceptor 12 [KO:K04298]
103084817  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
103084975  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103085198  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
103085303  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103085385  [KO:K04632]
103085631  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
103085845  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103085886  TLN1; LOW QUALITY PROTEIN: talin-1 [KO:K06271]
103085988  ITGA2; integrin alpha-2 [KO:K06481]
103086084  [KO:K06269] [EC:3.1.3.16]
103086189  FERMT3; fermitin family homolog 3 isoform X1 [KO:K17084]
103086280  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
103086383  ACTG1; actin, cytoplasmic 2 [KO:K05692]
103086425  BTK; tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
103086749  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
103087100  SNAP23; synaptosomal-associated protein 23 isoform X1 [KO:K08508]
103087259  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
103087566  TLN2; talin-2 [KO:K06271]
103088193  [KO:K06472]
103088422  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
103088639  [KO:K12757]
103088756  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103088758  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
103088976  [KO:K07836]
103089007  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
103089051  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
103089071  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
103089257  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103089268  MYL12B; myosin regulatory light chain 12B isoform X1 [KO:K12757]
103089427  VAMP8; vesicle-associated membrane protein 8 [KO:K08512]
103090456  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
103090681  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
103090934  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
103091057  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
103091169  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
103091387  PTGIR; prostacyclin receptor [KO:K04263]
103091388  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
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
lve00590  Arachidonic acid metabolism
lve04015  Rap1 signaling pathway
lve04020  Calcium signaling pathway
lve04151  PI3K-Akt signaling pathway
lve04610  Complement and coagulation cascades
lve05211  Renal cell carcinoma
KO pathway
ko04611   

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