KEGG   PATHWAY: mmf04611
Entry
mmf04611                    Pathway                                
Name
Platelet activation - Molossus molossus (Pallas's mastiff 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
mmf04611  Platelet activation
mmf04611

Other DBs
GO: 0030168
Organism
Molossus molossus (Pallas's mastiff bat) [GN:mmf]
Gene
118615653  TBXA2R; thromboxane A2 receptor [KO:K04264]
118628654  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
118642780  F2R; proteinase-activated receptor 1 [KO:K03914]
118615586  F2RL3; proteinase-activated receptor 4 [KO:K04236]
118633864  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
118638816  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
118628975  ARHGEF12; rho guanine nucleotide exchange factor 12 [KO:K07532]
118632939  RHOA; transforming protein RhoA [KO:K04513]
118618764  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
118630612  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
118627965  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
118630486  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
118639818  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
118623369  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
118618154  myosin regulatory light chain 12B isoform X1 [KO:K12757]
118620838  myosin regulatory light polypeptide 9-like isoform X1 [KO:K12757]
118633781  P2RX1; P2X purinoceptor 1 isoform X1 [KO:K05215]
118639809  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
118632878  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
118623451  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
118621173  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
118627890  STIM1; stromal interaction molecule 1 isoform X1 [KO:K16059]
118617212  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
118618547  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
118626541  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
118639281  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
118617494  P2RY1; P2Y purinoceptor 1 [KO:K04270]
118629502  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
118618293  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
118618784  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
118628278  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
118632151  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
118643394  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
118617164  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
118627541  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
118628048  RASGRP2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
118637043  RAP1A; ras-related protein Rap-1A [KO:K04353]
118624733  RAP1B; ras-related protein Rap-1b [KO:K07836]
118628425  amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
118634272  TLN2; talin-2 [KO:K06271]
118629626  TLN1; talin-1 [KO:K06271]
118633914  ITGA2B; integrin alpha-IIb [KO:K06476]
118634259  ITGB3; integrin beta-3 [KO:K06493]
118627677  FERMT3; fermitin family homolog 3 [KO:K17084]
118616349  FGA; fibrinogen alpha chain [KO:K03903]
118615871  FGB; fibrinogen beta chain isoform X1 [KO:K03904]
118615860  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
118617896  P2RY12; P2Y purinoceptor 12 [KO:K04298]
118632994  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
118620140  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
118637975  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
118620164  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
118642779  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
118630645  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
118631458  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
118617134  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
118623920  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
118639510  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
118631528  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
118642221  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
118638932  PTGIR; prostacyclin receptor [KO:K04263]
118618303  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
118618304  neuroendocrine secretory protein 55-like [KO:K04632]
118619840  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
118634593  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
118634929  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
118626166  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
118615793  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
118638390  vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
118635031  ACTG1; actin, cytoplasmic 2 [KO:K05692]
118616016  ACTB; actin, cytoplasmic 1 [KO:K05692]
118618720  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
118638452  ARHGAP35; rho GTPase-activating protein 35 isoform X1 [KO:K05732]
118637096  low affinity immunoglobulin gamma Fc region receptor III-like isoform X1 [KO:K06472]
118641349  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
118633930  COL1A1; collagen alpha-1(I) chain [KO:K06236]
118620424  COL1A2; collagen alpha-2(I) chain [KO:K06236]
118625680  COL3A1; collagen alpha-1(III) chain [KO:K19720]
118639045  GP6; platelet glycoprotein VI isoform X1 [KO:K06264]
118637357  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
118631367  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
118620959  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
118641528  ITGA2; integrin alpha-2 [KO:K06481]
118629439  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
118632927  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118626944  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118617106  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118626685  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
118642883  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118616460  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
118643531  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
118639621  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
118635763  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
118623334  VWF; von Willebrand factor [KO:K03900]
118616891  GP5; platelet glycoprotein V isoform X1 [KO:K06260]
118634419  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
118640078  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
118618810  GP9; platelet glycoprotein IX [KO:K06263]
118640620  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118619617  LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
118630299  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118638405  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118620067  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
118628194  GUCY1A2; guanylate cyclase soluble subunit alpha-2 isoform X1 [KO:K12318] [EC:4.6.1.2]
118615917  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
118622989  guanylate cyclase soluble subunit beta-2-like isoform X1 [KO:K12319] [EC:4.6.1.2]
118615581  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
118632751  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
118635511  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
118641186  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
118641187  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
118621004  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118621005  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118640210  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118642307  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
118641275  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
118634813  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
118628856  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
118637733  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
118638018  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
118630133  PTGS1; prostaglandin G/H synthase 1 [KO:K00509] [EC:1.14.99.1]
118619832  TBXAS1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
118634955  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
118630826  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
  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
mmf00590  Arachidonic acid metabolism
mmf04015  Rap1 signaling pathway
mmf04020  Calcium signaling pathway
mmf04151  PI3K-Akt signaling pathway
mmf04610  Complement and coagulation cascades
mmf05211  Renal cell carcinoma
KO pathway
ko04611   
LinkDB

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