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DEPARTAMENTO DE CIÊNCIAS DA VIDA ... - Estudo Geral

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12<br />

extracellular ligand and the cytoskeleton. So whether integrin-cytoskeleton bonds<br />

become reinforced depends upon the intracellular component and the mechanical<br />

properties of the microenvironment that make up this link.<br />

The activation of Src family kinases is involved in the ligand binding to integrins.<br />

This is supported because when applied a force, Src family have a rapid activation<br />

(within 300 ms) and was observed that Src family kinases Fyn and Src are required for<br />

rigidity sensing on fibronectin and vitronectin, respectively (Felsenfeld et al., 1999;<br />

Kostic and Sheetz, 2006; Na et al., 2008). The activation of the Src family kinases will<br />

bridge integrins to the cytoskeleton through talin (Duband et al., 1988; Felsenfeld et<br />

al., 1996; Schmidt et al., 1993; Zhang et al., 2008). Ligand binding couples integrins to<br />

the cytoskeleton once coupled to retrograde flowing actin, mechanical force on<br />

integrins could engage the integrin/ECM catch bond. Under stretching forces, Talin<br />

exposes vinculin binding sites (Figure 2C) that stabilize and recruit additional links to<br />

actin (del Rio et al., 2009). To restart the process the activation of FAK may reverse<br />

adhesions (Ilic et al., 1995; Zhang et al., 2008).

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