GP1b-IX-V activation signaling (Homo sapiens)

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1, 28310, 11131294-7cytosolRaf-114-3-3zeta dimerActive SRC (p-Y419)GPIb-IX-V:vWF:14-3-3-zeta14-3-3-zeta:Raf1SRCGPIb-IX-V:vWFActive c-Src:Raf1Filamin-AGPIb-IX-V:vWF:filamin-API3K-p85GPIb-IX-V:vWF:14-3-3-zeta:p85


Description

The platelet GPIb complex (GP1b-IX-V) together with GPVI are primarily responsible for regulating the initial adhesion of platelets to the damaged blood vessel and platelet activation. The importance of GPIb is demonstrated by the bleeding problems in patients with Bernard-Soulier syndrome where this receptor is either absent or defective. GP1b-IX-V binds von Willebrand Factor (vWF) to resting platelets, particularly under conditions of high shear stress. This transient interaction is the first stage of the vascular repair process. Activation of GP1b-IX-V on exposure of the fibrous matrix following atherosclerotic plaque rupture, or in occluded arteries, is a major contributory factor leading to thrombus formation leading to heart attack or stroke. GpIb also binds thrombin (Yamamoto et al. 1986), at a site distinct from the site of vWF binding, acting as a docking site for thrombin which then activates Proteinase Activated Receptors leading to enhanced platelet activation (Dormann et al. 2000).

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Bibliography

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  1. Feng S, Christodoulides N, Reséndiz JC, Berndt MC, Kroll MH.; ''Cytoplasmic domains of GpIbalpha and GpIbbeta regulate 14-3-3zeta binding to GpIb/IX/V.''; PubMed Europe PMC Scholia
  2. Munday AD, Berndt MC, Mitchell CA.; ''Phosphoinositide 3-kinase forms a complex with platelet membrane glycoprotein Ib-IX-V complex and 14-3-3zeta.''; PubMed Europe PMC Scholia
  3. Andrews RK, Harris SJ, McNally T, Berndt MC.; ''Binding of purified 14-3-3 zeta signaling protein to discrete amino acid sequences within the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex.''; PubMed Europe PMC Scholia
  4. Okita JR, Pidard D, Newman PJ, Montgomery RR, Kunicki TJ.; ''On the association of glycoprotein Ib and actin-binding protein in human platelets.''; PubMed Europe PMC Scholia
  5. Fantl WJ, Muslin AJ, Kikuchi A, Martin JA, MacNicol AM, Gross RW, Williams LT.; ''Activation of Raf-1 by 14-3-3 proteins.''; PubMed Europe PMC Scholia
  6. Ruggeri ZM, Mendolicchio GL.; ''Adhesion mechanisms in platelet function.''; PubMed Europe PMC Scholia
  7. Andrews RK, Berndt MC.; ''Platelet physiology and thrombosis.''; PubMed Europe PMC Scholia
  8. Du X, Fox JE, Pei S.; ''Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha.''; PubMed Europe PMC Scholia
  9. Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I.; ''The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.''; PubMed Europe PMC Scholia
  10. Cleghon V, Morrison DK.; ''Raf-1 interacts with Fyn and Src in a non-phosphotyrosine-dependent manner.''; PubMed Europe PMC Scholia
  11. Du X, Harris SJ, Tetaz TJ, Ginsberg MH, Berndt MC.; ''Association of a phospholipase A2 (14-3-3 protein) with the platelet glycoprotein Ib-IX complex.''; PubMed Europe PMC Scholia
  12. Williamson D, Pikovski I, Cranmer SL, Mangin P, Mistry N, Domagala T, Chehab S, Lanza F, Salem HH, Jackson SP.; ''Interaction between platelet glycoprotein Ibalpha and filamin-1 is essential for glycoprotein Ib/IX receptor anchorage at high shear.''; PubMed Europe PMC Scholia
  13. Ozaki Y, Asazuma N, Suzuki-Inoue K, Berndt MC.; ''Platelet GPIb-IX-V-dependent signaling.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
116423view09:11, 7 May 2021EweitzModified title
114766view16:25, 25 January 2021ReactomeTeamReactome version 75
113210view11:27, 2 November 2020ReactomeTeamReactome version 74
112434view15:38, 9 October 2020ReactomeTeamReactome version 73
101339view11:22, 1 November 2018ReactomeTeamreactome version 66
100877view20:56, 31 October 2018ReactomeTeamreactome version 65
100418view19:30, 31 October 2018ReactomeTeamreactome version 64
99968view16:14, 31 October 2018ReactomeTeamreactome version 63
99522view14:49, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93846view13:40, 16 August 2017ReactomeTeamreactome version 61
93403view11:22, 9 August 2017ReactomeTeamreactome version 61
87456view14:03, 22 July 2016MkutmonOntology Term : 'hemostasis pathway' added !
86489view09:19, 11 July 2016ReactomeTeamreactome version 56
83423view11:11, 18 November 2015ReactomeTeamVersion54
81626view13:10, 21 August 2015ReactomeTeamVersion53
77086view08:38, 17 July 2014ReactomeTeamFixed remaining interactions
76792view12:17, 16 July 2014ReactomeTeamFixed remaining interactions
76115view10:18, 11 June 2014ReactomeTeamRe-fixing comment source
75827view11:39, 10 June 2014ReactomeTeamReactome 48 Update
75188view09:38, 9 May 2014AnweshaFixing comment source for displaying WikiPathways description
74828view10:05, 30 April 2014ReactomeTeamReactome46
42046view21:52, 4 March 2011MaintBotAutomatic update
39849view05:52, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
14-3-3-zeta:

Raf1

ComplexREACT_24804 (Reactome)
14-3-3zeta

dimer

ComplexREACT_24853 (Reactome)
Active SRC (p-Y419) ProteinP12931-1 (UniProt)
Active c-Src:Raf1 ComplexREACT_24303 (Reactome)
Filamin-A ProteinP21333 (UniProt)
GPIb-IX-V:vWF ComplexREACT_24749 (Reactome)
GPIb-IX-V:vWF:

filamin-A

ComplexREACT_24471 (Reactome)
GPIb-IX-V:vWF:14-

3-3-zeta

ComplexREACT_24215 (Reactome)
GPIb-IX-V:vWF:14-

3-3-zeta:p85

ComplexREACT_24633 (Reactome)
PI3K-p85 ProteinP27986 (UniProt)
Raf-1 ProteinP04049 (UniProt)
SRC ProteinP12931-1 (UniProt)

Annotated Interactions

No annotated interactions

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