KEGG   PATHWAY: mcoc04611
Entry
mcoc04611                   Pathway                                
Name
Platelet activation - Mastomys coucha (southern multimammate mouse)
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
mcoc04611  Platelet activation
mcoc04611

Other DBs
GO: 0030168
Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116067909  Prkg2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
116068382  Orai1; calcium release-activated calcium channel protein 1 isoform X1 [KO:K16056]
116068700  Actb; actin, cytoplasmic 1 [KO:K05692]
116069116  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
116069491  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116069565  F2rl3; proteinase-activated receptor 4 isoform X1 [KO:K04236]
116069698  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
116069762  Mylk3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
116069817  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
116070251  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
116070458  Itgb1; integrin beta-1 [KO:K05719]
116072321  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
116072449  Tln2; talin-2 isoform X1 [KO:K06271]
116072951  Arhgef12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
116073648  Mapk6; mitogen-activated protein kinase 6 [KO:K04371] [EC:2.7.11.24]
116073929  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116073981  Rhoa; transforming protein RhoA [KO:K04513]
116074200  Gucy1a2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
116074574  Fyn; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
116075101  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
116075516  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116075536  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116075736  Rap1b; ras-related protein Rap-1b [KO:K07836]
116076076  Tbxa2r; thromboxane A2 receptor [KO:K04264]
116076104  Ppp1r12a; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
116076329  [KO:K04513]
116076843  Gna13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
116076922  Itgb3; integrin beta-3 [KO:K06493]
116077083  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
116077708  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
116077765  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
116077791  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
116077916  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
116078035  Gp1ba; platelet glycoprotein Ib alpha chain [KO:K06261]
116078214  Itga2b; integrin alpha-IIb [KO:K06476]
116078513  P2rx1; P2X purinoceptor 1 isoform X1 [KO:K05215]
116078726  Col1a1; collagen alpha-1(I) chain [KO:K06236]
116078777  Actg1; actin, cytoplasmic 2 [KO:K05692]
116079067  Adcy6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
116079614  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
116079663  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
116079779  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116079916  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
116080601  Rock2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
116081405  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
116081489  Mylk4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
116082049  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
116083244  Itga2; integrin alpha-2 [KO:K06481]
116083372  F2r; proteinase-activated receptor 1 [KO:K03914]
116083593  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
116083721  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116084111  Adcy4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
116084214  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
116084458  [KO:K12319] [EC:4.6.1.2]
116085641  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116085699  Gp1bb; platelet glycoprotein Ib beta chain [KO:K06262]
116085785  Gp5; platelet glycoprotein V [KO:K06260]
116085852  Mylk; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
116085856  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
116086826  Rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
116088122  Lyn; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
116088383  Col3a1; collagen alpha-1(III) chain [KO:K19720]
116088560  Btk; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
116088889  Myl12b; myosin regulatory light chain 12B [KO:K12757]
116088890  [KO:K12757]
116089766  Apbb1ip; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
116090081  Ptgs1; prostaglandin G/H synthase 1 [KO:K00509] [EC:1.14.99.1]
116090682  Rasgrp1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
116090695  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
116090743  Pla2g4b; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
116090754  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
116090758  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
116090760  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
116090768  Snap23; synaptosomal-associated protein 23 isoform X1 [KO:K08508]
116090998  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
116090999  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
116091182  Mylk2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
116091289  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
116091495  [KO:K04632]
116091496  [KO:K04632]
116091905  Adamts13; A disintegrin and metalloproteinase with thrombospondin motifs 13 isoform X1 [KO:K08627] [EC:3.4.24.87]
116092238  F2; prothrombin isoform X1 [KO:K01313] [EC:3.4.21.5]
116092922  P2ry12; P2Y purinoceptor 12 [KO:K04298]
116092927  [KO:K04353]
116092937  P2ry1; P2Y purinoceptor 1 [KO:K04270]
116093028  Gucy1b1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
116093029  Gucy1a1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
116093033  Fgg; fibrinogen gamma chain isoform X1 [KO:K03905]
116093039  Fgb; fibrinogen beta chain isoform X1 [KO:K03904]
116093571  Rap1a; ras-related protein Rap-1A isoform X1 [KO:K04353]
116093617  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
116093928  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116094086  Fga; fibrinogen alpha chain [KO:K03903]
116095037  Prkci; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
116095058  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116095810  Prkcz; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
116095900  Tln1; talin-1 [KO:K06271]
116096465  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
116097037  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116097497  [KO:K04630]
116097543  Nos3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
116098228  Gp9; platelet glycoprotein IX [KO:K06263]
116098542  Col1a2; collagen alpha-2(I) chain [KO:K06236]
116098761  Tbxas1; thromboxane-A synthase isoform X1 [KO:K01832] [EC:5.3.99.5]
116099080  Vamp8; vesicle-associated membrane protein 8 [KO:K08512]
116099290  [KO:K05692]
116099362  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116099616  Vwf; von Willebrand factor isoform X1 [KO:K03900]
116099798  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116100272  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
116100719  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
116101539  Gp6; LOW QUALITY PROTEIN: platelet glycoprotein VI [KO:K06264]
116101687  Arhgap35; rho GTPase-activating protein 35 [KO:K05732]
116101704  Ptgir; prostacyclin receptor [KO:K04263]
116101743  Vasp; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
116101825  Arhgef1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
116101889  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116102693  Stim1; stromal interaction molecule 1 isoform X1 [KO:K16059]
116102969  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116103299  Fcgr2a; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
116103326  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
116103368  Fcer1g; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
116103453  Rasgrp2; RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
116103465  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
116103475  Fermt3; fermitin family homolog 3 [KO:K17084]
116103624  [KO:K04634]
116103727  Prkg1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
116104026  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116104637  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
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
mcoc00590  Arachidonic acid metabolism
mcoc04015  Rap1 signaling pathway
mcoc04020  Calcium signaling pathway
mcoc04151  PI3K-Akt signaling pathway
mcoc04610  Complement and coagulation cascades
mcoc05211  Renal cell carcinoma
KO pathway
ko04611   

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