KEGG   PATHWAY: mjv04611
Entry
mjv04611                    Pathway                                
Name
Platelet activation - Manis javanica (Malayan pangolin)
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
mjv04611  Platelet activation
mjv04611

Other DBs
GO: 0030168
Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108383250  RHOA; transforming protein RhoA [KO:K04513]
108383520  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
108383561  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108383641  F2R; proteinase-activated receptor 1 isoform X2 [KO:K03914]
108384319  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
108384363  STIM1; stromal interaction molecule 1 isoform X2 [KO:K16059]
108384766  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
108385124  COL1A1; collagen alpha-1(I) chain [KO:K06236]
108385316  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
108385404  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
108385409  PLA2G4B; cytosolic phospholipase A2 beta isoform X3 [KO:K16342] [EC:3.1.1.4]
108385414  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X2 [KO:K16342] [EC:3.1.1.4]
108386155  PRKCZ; protein kinase C zeta type isoform X2 [KO:K18952] [EC:2.7.11.13]
108386296  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
108387338  P2RY12; P2Y purinoceptor 12 isoform X1 [KO:K04298]
108387546  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
108388509  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
108388549  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
108390365  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108390400  [KO:K16056]
108390475  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
108390484  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108391302  ROCK1; rho-associated protein kinase 1 isoform X3 [KO:K04514] [EC:2.7.11.39]
108391841  NOS3; nitric oxide synthase 3 isoform X2 [KO:K13242] [EC:1.14.13.39]
108392084  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
108392407  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
108392468  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
108393093  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
108393155  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
108393272  TBXA2R; thromboxane A2 receptor [KO:K04264]
108393654  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
108393666  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X4 [KO:K12330]
108393746  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
108393851  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
108394257  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X5 [KO:K05858] [EC:3.1.4.11]
108394259  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
108394635  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
108394636  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
108395354  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
108395546  RAP1A; ras-related protein Rap-1A [KO:K04353]
108395952  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 [KO:K04958]
108395975  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
108396063  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
108396080  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
108396202  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
108396333  [KO:K06264]
108396371  RASGRP2; RAS guanyl-releasing protein 2 [KO:K12361]
108396428  P2RY1; P2Y purinoceptor 1 [KO:K04270]
108396587  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
108396721  ADCY5; adenylate cyclase type 5 isoform X4 [KO:K08045] [EC:4.6.1.1]
108396833  GP9; platelet glycoprotein IX [KO:K06263]
108396895  F2RL3; proteinase-activated receptor 4 [KO:K04236]
108397126  COL3A1; collagen alpha-1(III) chain [KO:K19720]
108397161  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
108397345  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
108397433  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108397669  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
108397835  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
108398385  ADAMTS13; A disintegrin and metalloproteinase with thrombospondin motifs 13 isoform X1 [KO:K08627] [EC:3.4.24.87]
108398405  COL1A2; collagen alpha-2(I) chain [KO:K06236]
108398454  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108398868  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
108399739  GP5; platelet glycoprotein V [KO:K06260]
108400163  SNAP23; synaptosomal-associated protein 23 [KO:K08508]
108400464  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
108400557  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
108400663  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
108400984  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
108401068  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
108401443  [KO:K12319] [EC:4.6.1.2]
108401592  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
108401653  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
108401717  APBB1IP; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
108402114  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
108402518  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
108402874  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
108402938  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X2 [KO:K04960]
108403293  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform X1 [KO:K04959]
108403296  F2; prothrombin isoform X1 [KO:K01313] [EC:3.4.21.5]
108404165  P2RX1; P2X purinoceptor 1 isoform X1 [KO:K05215]
108404459  VWF; von Willebrand factor isoform X1 [KO:K03900]
108405198  TBXAS1; thromboxane-A synthase [KO:K01832] [EC:5.3.99.5]
108405277  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
108405893  [KO:K08512]
108406139  PTGIR; prostacyclin receptor isoform X1 [KO:K04263]
108406177  [KO:K04632]
108406179  [KO:K04632]
108406293  FGB; fibrinogen beta chain isoform X1 [KO:K03904]
108406307  FGG; fibrinogen gamma chain [KO:K03905]
108406886  TLN1; talin-1 isoform X1 [KO:K06271]
108407176  GUCY1A2; guanylate cyclase soluble subunit alpha-2 isoform X1 [KO:K12318] [EC:4.6.1.2]
108407219  [KO:K12757]
108407220  [KO:K12757]
108407296  ADCY7; adenylate cyclase type 7 isoform X2 [KO:K08047] [EC:4.6.1.1]
108407356  RAP1B; ras-related protein Rap-1b [KO:K07836]
108407569  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
108407585  FERMT3; fermitin family homolog 3 [KO:K17084]
108408094  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X5 [KO:K06270]
108408257  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma isoform X1 [KO:K07983]
108408343  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
108408486  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
108408488  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
108408578  TLN2; talin-2 isoform X1 [KO:K06271]
108409101  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
108409197  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
108409724  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
108410024  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
108410188  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
108410207  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
118967469  GP1BB; platelet glycoprotein Ib beta chain [KO:K06262]
118968537  [KO:K05854] [EC:2.7.10.2]
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
mjv00590  Arachidonic acid metabolism
mjv04015  Rap1 signaling pathway
mjv04020  Calcium signaling pathway
mjv04151  PI3K-Akt signaling pathway
mjv04610  Complement and coagulation cascades
mjv05211  Renal cell carcinoma
KO pathway
ko04611   

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