Fig. 4.

Talin and PIP5KIγa/c interact during focal contact assembly. Upon cell activation, PIP5KIγa/c undergoes phosphorylation on Tyr644 by Src kinase, which also associates with it. Both events are positively regulated by FAK kinase. When phosphorylated, PIP5KIγa/c binds to the FERM domain located in the globular N-terminal part of talin. The kinase produces PI(4,5)P₂, which binds to the FERM domain of talin and relieves autoinhibitory interaction of the talin head with rod. At these conditions, talin is able to bind β-integrins, inducing additionally their aggregation and activation. Intracellularly, talin binds actin filaments, which enables the formation of stress fibers. The Tyr644 can be dephosphorylated by Shp-1, which associates with PIP5KIγ. The activity of Shp-1 is inhibited by PI(4,5)P₂ favoring the lipid accumulation. On the other hand, the binding of β-integrin to talin can be inhibited by phosphorylation of β-integrin by Src kinase