Integrin alphaIIb beta3 activation

Stable Identifier
R-HSA-354077
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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The interaction between talin and integrin alphaIIb beta3 breaks the putative salt bridge between the alphaIIb (R995) and beta3 (D723) integrin chains and induces conformational changes in their external domains increasing their affinity for fibrinogen and other ECM ligands. Breaking of this salt bridge is necessary but not sufficient for full activation.
The Talin F3 subdomain of the FERM domain has a phosphotyrosine binding (PTB) domain fold. This domain interacts with the membrane-proximal (MP) region within the integrin beta3 chain. The primary function of this interaction is to provide an initial strong linkage between talin and integrin and this interaction holds the key to the molecular recognition required for activation. In platelets SRC kinase and its negative regulator CSK associates constitutively with integrin alphaIIbbeta3. SRC is involved in alphaIIbbeta3 dependent activation of SYK, and both SRC and SYK are required to initiate cytoskeletal events responsible for platelet spreading on fibrinogen.

Literature References
PubMed ID Title Journal Year
14754902 Integrin activation

Calderwood, DA

J Cell Sci 2004
10446041 Integrin signaling

Giancotti, FG, Ruoslahti, E

Science 1999
17218263 Structural basis of integrin activation by talin

Wegener, KL, Partridge, AW, Han, J, Pickford, AR, Liddington, RC, Ginsberg, MH, Campbell, ID

Cell 2007
11940607 Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton

Obergfell, A, Eto, K, Mocsai, A, Buensuceso, C, Moores, SL, Brugge, JS, Lowell, CA, Shattil, SJ

J Cell Biol 2002
18434644 Talin at a glance

Critchley, DR, Gingras, AR

J Cell Sci 2008
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