KEGG   PATHWAY: lcat04611
Entry
lcat04611                   Pathway                                
Name
Platelet activation - Lemur catta (Ring-tailed lemur)
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
lcat04611  Platelet activation
lcat04611

Other DBs
GO: 0030168
Organism
Lemur catta (Ring-tailed lemur) [GN:lcat]
Gene
123633528  TBXA2R; thromboxane A2 receptor [KO:K04264]
123642660  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
123648568  F2R; proteinase-activated receptor 1 [KO:K03914]
123640004  F2RL3; proteinase-activated receptor 4 [KO:K04236]
123650582  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
123624056  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
123641456  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
123623278  RHOA; transforming protein RhoA [KO:K04513]
123643616  transforming protein RhoA-like [KO:K04513]
123621906  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
123636599  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
123626056  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
123642855  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
123636756  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
123639486  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
123621565  myosin regulatory light polypeptide 9 [KO:K12757]
123621566  myosin regulatory light chain 12B [KO:K12757]
123628100  myosin regulatory light polypeptide 9-like [KO:K12757]
123620634  P2RX1; P2X purinoceptor 1 [KO:K05215]
123626085  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
123623574  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123639915  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
123632820  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
123642324  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
123630468  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
123638169  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
123622844  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
123625139  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
123630189  P2RY1; P2Y purinoceptor 1 [KO:K04270]
123646308  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
123622057  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
123622065  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
123624366  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
123641430  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
123635996  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
123630254  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
123621915  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
123641412  RASGRP2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
123635037  RAP1A; ras-related protein Rap-1A [KO:K04353]
123639540  RAP1B; ras-related protein Rap-1b [KO:K07836]
123626234  amyloid beta A4 precursor protein-binding family B member 1-interacting protein isoform X1 [KO:K17704]
123630651  TLN2; LOW QUALITY PROTEIN: talin-2 [KO:K06271]
123646154  TLN1; talin-1 isoform X1 [KO:K06271]
123621031  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
123620572  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
123641437  FERMT3; fermitin family homolog 3 isoform X1 [KO:K17084]
123638506  FGA; fibrinogen alpha chain [KO:K03903]
123638505  FGB; fibrinogen beta chain [KO:K03904]
123638507  FGG; fibrinogen gamma chain [KO:K03905]
123630182  P2RY12; P2Y purinoceptor 12 [KO:K04298]
123623249  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
123647150  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
123635002  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
123647256  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
123648063  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
123636670  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
123650680  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123630472  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
123640442  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
123625466  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123644339  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
123632319  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
123623918  PTGIR; prostacyclin receptor [KO:K04263]
123622308  neuroendocrine secretory protein 55-like [KO:K04632]
123622310  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
123647726  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
123650941  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
123650942  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
123637748  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
123635476  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123623950  LOW QUALITY PROTEIN: vasodilator-stimulated phosphoprotein [KO:K06274]
123631525  ACTB; actin, cytoplasmic 1 [KO:K05692]
123650686  ACTG1; actin, cytoplasmic 2 [KO:K05692]
123622361  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
123623910  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
123646461  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
123647251  COL1A2; collagen alpha-2(I) chain [KO:K06236]
123620722  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
123643683  COL3A1; collagen alpha-1(III) chain [KO:K19720]
123624669  GP6; platelet glycoprotein VI [KO:K06264]
123635221  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
123644610  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
123633175  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
123648225  ITGA2; integrin alpha-2 [KO:K06481]
123626683  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
123629856  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123630278  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123634506  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
123639706  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123648578  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123634187  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
123637973  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
123625473  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
123640137  VWF; von Willebrand factor [KO:K03900]
123630406  GP5; platelet glycoprotein V [KO:K06260]
123621241  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
123626264  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
123625645  GP9; platelet glycoprotein IX isoform X1 [KO:K06263]
123624322  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123627566  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123643797  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123647518  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
123638509  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
123641753  GUCY1A2; guanylate cyclase soluble subunit alpha-2 isoform X1 [KO:K12318] [EC:4.6.1.2]
123638510  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
123649083  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
123650455  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
123627373  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
123632869  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123632871  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123640770  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123640771  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
123632778  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
123626228  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123629407  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
123630054  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
123630120  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
123630132  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
123626765  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
123646101  PTGS1; prostaglandin G/H synthase 1 [KO:K00509] [EC:1.14.99.1]
123647657  TBXAS1; thromboxane-A synthase [KO:K01832] [EC:5.3.99.5]
123630230  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
123646331  synaptosomal-associated protein 23-like [KO:K08508]
123637125  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
lcat00590  Arachidonic acid metabolism
lcat04015  Rap1 signaling pathway
lcat04020  Calcium signaling pathway
lcat04151  PI3K-Akt signaling pathway
lcat04610  Complement and coagulation cascades
lcat05211  Renal cell carcinoma
KO pathway
ko04611   
LinkDB

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