KEGG   PATHWAY: ko04611
ko04611                     Pathway                                
Platelet activation
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.
Organismal Systems; Immune system
Pathway map
ko04611  Platelet activation

Other DBs
GO: 0030168
K04264  thromboxane A2 receptor
K01313  coagulation factor II (thrombin) [EC:]
K03914  coagulation factor II (thrombin) receptor
K04236  coagulation factor II (thrombin) receptor-like 3
K04639  guanine nucleotide-binding protein subunit alpha-13
K12330  Rho guanine nucleotide exchange factor 1
K07532  Rho guanine nucleotide exchange factor 12
K04513  Ras homolog gene family, member A
K04514  Rho-associated protein kinase 1 [EC:]
K17388  Rho-associated protein kinase 2 [EC:]
K06269  serine/threonine-protein phosphatase PP1 catalytic subunit [EC:]
K06270  protein phosphatase 1 regulatory subunit 12A
K12757  myosin regulatory light chain 12
K05215  P2X purinoceptor 1
K16056  calcium release-activated calcium channel protein 1
K04958  inositol 1,4,5-triphosphate receptor type 1
K04959  inositol 1,4,5-triphosphate receptor type 2
K04960  inositol 1,4,5-triphosphate receptor type 3
K16059  stromal interaction molecule 1
K00907  myosin-light-chain kinase [EC:]
K04270  P2Y purinoceptor 1
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K05858  phosphatidylinositol phospholipase C, beta [EC:]
K18952  atypical protein kinase C zeta type [EC:]
K06069  atypical protein kinase C iota type [EC:]
K04350  RAS guanyl-releasing protein 1
K12361  RAS guanyl-releasing protein 2
K04353  Ras-related protein Rap-1A
K07836  Ras-related protein Rap-1B
K17704  amyloid beta A4 precursor protein-binding family B member 1-interacting protein
K06271  talin
K06476  integrin alpha 2B
K06493  integrin beta 3
K17084  kindlin 3
K03903  fibrinogen alpha chain
K03904  fibrinogen beta chain
K03905  fibrinogen gamma chain
K04298  P2Y purinoceptor 12
K04630  guanine nucleotide-binding protein G(i) subunit alpha
K08041  adenylate cyclase 1 [EC:]
K08042  adenylate cyclase 2 [EC:]
K08043  adenylate cyclase 3 [EC:]
K08044  adenylate cyclase 4 [EC:]
K08045  adenylate cyclase 5 [EC:]
K08046  adenylate cyclase 6 [EC:]
K08047  adenylate cyclase 7 [EC:]
K08048  adenylate cyclase 8 [EC:]
K08049  adenylate cyclase 9 [EC:]
K04263  prostacyclin receptor
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K21289  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:]
K21290  phosphoinositide-3-kinase regulatory subunit 5/6
K04345  protein kinase A [EC:]
K06274  vasodilator-stimulated phosphoprotein
K05692  actin beta/gamma 1
K05704  tyrosine-protein kinase Src [EC:]
K05732  glucocorticoid receptor DNA-binding factor 1
K06472  low affinity immunoglobulin gamma Fc receptor II-a
K05855  spleen tyrosine kinase [EC:]
K06236  collagen type I alpha
K19720  collagen type III alpha
K06264  platelet glycoprotein VI
K07983  high affinity immunoglobulin epsilon receptor subunit gamma
K05854  tyrosine-protein kinase Lyn [EC:]
K05703  tyrosine-protein kinase Fyn [EC:]
K06481  integrin alpha 2
K05719  integrin beta 1
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K07361  lymphocyte cytosolic protein 2
K05859  phosphatidylinositol phospholipase C, gamma-2 [EC:]
K07370  Bruton agammaglobulinemia tyrosine kinase [EC:]
K03900  von Willebrand factor
K06260  platelet glycoprotein V
K06261  platelet glycoprotein Ib alpha chain
K06262  platelet glycoprotein Ib beta chain
K06263  platelet glycoprotein IX
K04456  RAC serine/threonine-protein kinase [EC:]
K13242  nitric-oxide synthase, endothelial [EC:]
K12318  guanylate cyclase soluble subunit alpha [EC:]
K12319  guanylate cyclase soluble subunit beta [EC:]
K07376  cGMP-dependent protein kinase 1 [EC:]
K19477  cGMP-dependent protein kinase 2 [EC:]
K04441  p38 MAP kinase [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K16342  cytosolic phospholipase A2 [EC:]
K00509  prostaglandin-endoperoxide synthase 1 [EC:]
K01832  thromboxane-A synthase [EC:]
K08508  synaptosomal-associated protein 23
K08512  vesicle-associated membrane protein 8
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
Li Z, Delaney MK, O'Brien KA, Du X
Signaling during platelet adhesion and activation.
Arterioscler Thromb Vasc Biol 30:2341-9 (2010)
Broos K, De Meyer SF, Feys HB, Vanhoorelbeke K, Deckmyn H
Blood platelet biochemistry.
Thromb Res 129:245-9 (2012)
Jurk K, Kehrel BE
Platelets: physiology and biochemistry.
Semin Thromb Hemost 31:381-92 (2005)
Offermanns S
Activation of platelet function through G protein-coupled receptors.
Circ Res 99:1293-304 (2006)
Varga-Szabo D, Pleines I, Nieswandt B
Cell adhesion mechanisms in platelets.
Arterioscler Thromb Vasc Biol 28:403-12 (2008)
Yin H, Liu J, Li Z, Berndt MC, Lowell CA, Du X
Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway.
Blood 112:1139-46 (2008)
Bergmeier W, Stefanini L
Novel molecules in calcium signaling in platelets.
J Thromb Haemost 7 Suppl 1:187-90 (2009)
Cifuni SM, Wagner DD, Bergmeier W
CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets.
Blood 112:1696-703 (2008)
Heemskerk JW, Mattheij NJ, Cosemans JM
Platelet-based coagulation: different populations, different functions.
J Thromb Haemost 11:2-16 (2013)
Rivera J, Lozano ML, Navarro-Nunez L, Vicente V
Platelet receptors and signaling in the dynamics of thrombus formation.
Haematologica 94:700-11 (2009)
Banno A, Ginsberg MH
Integrin activation.
Biochem Soc Trans 36:229-34 (2008)
Angiolillo DJ, Ferreiro JL
Platelet adenosine diphosphate P2Y12 receptor antagonism: benefits and limitations of current treatment strategies and future directions.
Rev Esp Cardiol 63:60-76 (2010)
Joo SJ
Mechanisms of Platelet Activation and Integrin alphaIIbeta3.
Korean Circ J 42:295-301 (2012)
Harper MT, Poole AW
Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation.
J Thromb Haemost 8:454-62 (2010)
Fitch-Tewfik JL, Flaumenhaft R
Platelet granule exocytosis: a comparison with chromaffin cells.
Front Endocrinol (Lausanne) 4:77 (2013)
Boylan B, Gao C, Rathore V, Gill JC, Newman DK, Newman PJ
Identification of FcgammaRIIa as the ITAM-bearing receptor mediating alphaIIbbeta3 outside-in integrin signaling in human platelets.
Blood 112:2780-6 (2008)
ko00590  Arachidonic acid metabolism
ko04015  Rap1 signaling pathway
ko04020  Calcium signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04610  Complement and coagulation cascades
ko05211  Renal cell carcinoma

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