Integrin alphaIIb beta3 activation

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.<br>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.

Talin与整合素αIIbβ3之间的相互作用中断了αIIb（R995）与β3（D723）整合素链之间假定的盐桥，并诱导其外域发生构象变化，从而增强其对纤维蛋白原及其他细胞外基质配体的亲和力。此盐桥的断裂对于完全活化是必要的，但非充分条件。Talin F3亚域的FERM结构域含有磷酸酪氨酸结合（PTB）结构域折叠。此结构域与整合素β3链中的膜近端（MP）区域相互作用。此相互作用的初级功能是为talin与整合素之间提供初步的强烈连接，这一连接是活化过程中所需分子识别的关键。在血小板中，SRC激酶及其负调控因子CSK与整合素αIIbbeta3构成性结合。SRC参与αIIbbeta3依赖性的SYK活化，而SRC和SYK均为启动负责血小板在纤维蛋白原上扩散的细胞骨架事件的起始所必需。