KEGG   PATHWAY: ppad04611
Entry
ppad04611                   Pathway                                
Name
Platelet activation - Panthera pardus (leopard)
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
ppad04611  Platelet activation
ppad04611

Other DBs
GO: 0030168
Organism
Panthera pardus (leopard) [GN:ppad]
Gene
109255918  TBXA2R; thromboxane A2 receptor isoform X1 [KO:K04264]
109245108  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
109274968  F2R; proteinase-activated receptor 1 isoform X1 [KO:K03914]
109247554  F2RL3; proteinase-activated receptor 4 isoform X1 [KO:K04236]
109277047  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
109257994  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
109278500  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
109247805  RHOA; transforming protein RhoA [KO:K04513]
109248559  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
109268495  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
109266491  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
109246846  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
109277658  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
109270552  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
109248585  myosin regulatory light polypeptide 9 isoform X1 [KO:K12757]
109248586  myosin regulatory light chain 12B [KO:K12757]
109255209  P2RX1; P2X purinoceptor 1 [KO:K05215]
109277687  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
109254652  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
109268756  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
109271454  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
109267119  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
109249481  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
109266499  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
109270987  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
109272590  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
109261403  P2RY1; P2Y purinoceptor 1 [KO:K04270]
109275364  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
109246661  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
109274721  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109274722  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
109263166  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
109273956  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
109262118  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
109263183  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
109246682  RASGRP2; RAS guanyl-releasing protein 2 [KO:K12361]
109272045  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
109259557  ras-related protein Rap-1b [KO:K07836]
109270479  RAP1B; ras-related protein Rap-1b [KO:K07836]
109256871  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
109270161  TLN1; talin-1 isoform X1 [KO:K06271]
109262894  TLN2; talin-2 [KO:K06271]
109258195  ITGA2B; integrin alpha-IIb [KO:K06476]
109246650  FERMT3; fermitin family homolog 3 [KO:K17084]
109262500  FGA; fibrinogen alpha chain [KO:K03903]
109262501  FGB; fibrinogen beta chain [KO:K03904]
109262499  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
109261220  P2RY12; P2Y purinoceptor 12 isoform X1 [KO:K04298]
109247840  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
109268145  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
109272000  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
109267948  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
109267830  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
109267527  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
109254969  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
109266493  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
109249043  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
109270953  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109273118  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
109278247  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
109253190  PTGIR; prostacyclin receptor [KO:K04263]
109253465  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like isoform X1 [KO:K04632]
109253466  neuroendocrine secretory protein 55 [KO:K04632]
109268077  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
109245881  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
109246080  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
109246175  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
109253991  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
109253231  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
109276785  ACTG1; actin, cytoplasmic 2 [KO:K05692]
109251167  ACTB; actin, cytoplasmic 1 [KO:K05692]
109272472  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
109253182  ARHGAP35; rho GTPase-activating protein 35 isoform X1 [KO:K05732]
109275517  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
109263702  COL1A2; collagen alpha-2(I) chain isoform X1 [KO:K06236]
109247299  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
109274385  COL3A1; collagen alpha-1(III) chain isoform X1 [KO:K19720]
109259935  GP6; platelet glycoprotein VI isoform X1 [KO:K06264]
109257267  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
109250302  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
109263555  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
109275896  ITGA2; integrin alpha-2 [KO:K06481]
109276308  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
109274075  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109275159  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109259912  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109266953  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109275060  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
109247606  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109267478  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
109245637  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
109258849  BTK; tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
109276146  VWF; von Willebrand factor [KO:K03900]
109266580  GP5; platelet glycoprotein V [KO:K06260]
109246019  GP1BA; LOW QUALITY PROTEIN: platelet glycoprotein Ib alpha chain [KO:K06261]
109258642  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
109256073  platelet glycoprotein IX-like [KO:K06263]
109256074  GP9; platelet glycoprotein IX [KO:K06263]
109256570  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109251379  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109257810  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109252365  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
109262490  GUCY1A3; guanylate cyclase soluble subunit alpha-3 [KO:K12318] [EC:4.6.1.2]
109278730  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
109262488  GUCY1B3; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
109255410  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
109276981  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
109265257  MAPK11; LOW QUALITY PROTEIN: mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
109265767  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
109271512  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
109271515  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
109259699  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109261343  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109263108  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
109263110  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
109263111  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
109253583  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
109269849  PTGS1; prostaglandin G/H synthase 1 [KO:K00509] [EC:1.14.99.1]
109269096  TBXAS1; thromboxane-A synthase [KO:K01832] [EC:5.3.99.5]
109263100  SNAP23; synaptosomal-associated protein 23 isoform X1 [KO:K08508]
109263878  VAMP8; vesicle-associated membrane protein 8 isoform X1 [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
ppad00590  Arachidonic acid metabolism
ppad04015  Rap1 signaling pathway
ppad04020  Calcium signaling pathway
ppad04151  PI3K-Akt signaling pathway
ppad04610  Complement and coagulation cascades
ppad05211  Renal cell carcinoma
KO pathway
ko04611   
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