KEGG   PATHWAY: elk04611
Entry
elk04611                    Pathway                                
Name
Platelet activation - Enhydra lutris kenyoni (northern sea otter)
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
elk04611  Platelet activation
elk04611

Other DBs
GO: 0030168
Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111161834  thromboxane A2 receptor [KO:K04264]
111149799  prothrombin isoform X1 [KO:K01313] [EC:3.4.21.5]
111148319  proteinase-activated receptor 1 [KO:K03914]
111144372  LOW QUALITY PROTEIN: proteinase-activated receptor 4 [KO:K04236]
111158131  guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
111139489  rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
111153798  rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
111144026  transforming protein RhoA isoform X1 [KO:K04513]
111142435  rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
111154090  rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
111156372  serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
111144767  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
111149674  serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
111139288  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
111141992  protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
111142542  myosin regulatory light polypeptide 9 isoform X1 [KO:K12757]
111142543  myosin regulatory light chain 12B [KO:K12757]
111158764  P2X purinoceptor 1 isoform X1 [KO:K05215]
111156453  calcium release-activated calcium channel protein 1 isoform X1 [KO:K16056]
111144005  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
111159979  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
111152507  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
111159392  stromal interaction molecule 1 isoform X1 [KO:K16059]
111156670  myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
111141709  myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
111154981  myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
111157401  myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
111150185  P2Y purinoceptor 1 [KO:K04270]
111153498  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
111141432  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
111162302  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
111141620  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
111150005  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
111154565  protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
111148089  protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
111140724  RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
111149468  RAS guanyl-releasing protein 2 isoform X1 [KO:K12361]
111143648  ras-related protein Rap-1A isoform X1 [KO:K04353]
111141969  ras-related protein Rap-1b [KO:K07836]
111139709  amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
111153217  talin-2 isoform X1 [KO:K06271]
111146277  talin-1 [KO:K06271]
111158126  integrin alpha-IIb isoform X1 [KO:K06476]
111158107  integrin beta-3 [KO:K06493]
111149527  fermitin family homolog 3 [KO:K17084]
111154842  fibrinogen alpha chain [KO:K03903]
111157895  fibrinogen beta chain [KO:K03904]
111153669  fibrinogen gamma chain isoform X1 [KO:K03905]
111148951  P2Y purinoceptor 12 [KO:K04298]
111155312  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
111143783  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
111143343  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
111157054  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111153427  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
111154044  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
111162403  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
111155044  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111157825  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
111157326  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
111146667  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
111156133  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
111160733  prostacyclin receptor [KO:K04263]
111141614  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
111141312  neuroendocrine secretory protein 55 [KO:K04632]
111155215  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
111161090  phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
111161150  phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
111162516  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
111143399  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111160553  vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
111160249  actin, cytoplasmic 2 [KO:K05692]
111145734  actin, cytoplasmic 1 [KO:K05692]
111141563  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
111160649  LOW QUALITY PROTEIN: rho GTPase-activating protein 35 [KO:K05732]
111153538  tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
111151317  collagen alpha-1(I) chain isoform X1 [KO:K06236]
111147195  collagen alpha-2(I) chain [KO:K06236]
111148079  collagen alpha-1(III) chain [KO:K19720]
111140055  platelet glycoprotein VI isoform X1 [KO:K06264]
111138962  high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
111155370  tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
111158275  tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
111141135  integrin alpha-2 [KO:K06481]
111155558  integrin beta-1 isoform X1 [KO:K05719]
111155003  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111147545  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111154641  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111143470  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
111155224  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111143790  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111140829  lymphocyte cytosolic protein 2 [KO:K07361]
111152978  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
111159177  tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
111159823  von Willebrand factor isoform X1 [KO:K03900]
111155034  LOW QUALITY PROTEIN: platelet glycoprotein V [KO:K06260]
111161057  platelet glycoprotein Ib alpha chain [KO:K06261]
111142672  LOW QUALITY PROTEIN: platelet glycoprotein Ib beta chain [KO:K06262]
111159031  platelet glycoprotein IX [KO:K06263]
111161374  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111148765  RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111150885  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111154402  nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
111153821  LOW QUALITY PROTEIN: guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
111155838  guanylate cyclase soluble subunit alpha-3 [KO:K12318] [EC:4.6.1.2]
111147095  LOW QUALITY PROTEIN: guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
111154115  guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
111145213  cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
111149130  cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
111152267  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
111157625  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111157628  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
111152183  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111162236  LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111142759  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111150782  cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
111140157  LOW QUALITY PROTEIN: cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
111162039  cytosolic phospholipase A2 beta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
111140619  cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
111160468  cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
111145816  prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
111151949  thromboxane-A synthase [KO:K01832] [EC:5.3.99.5]
111160637  synaptosomal-associated protein 23 [KO:K08508]
111148066  vesicle-associated membrane protein 8 [KO:K08512]
111148071  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
elk00590  Arachidonic acid metabolism
elk04015  Rap1 signaling pathway
elk04020  Calcium signaling pathway
elk04151  PI3K-Akt signaling pathway
elk04610  Complement and coagulation cascades
elk05211  Renal cell carcinoma
KO pathway
ko04611   
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