FIGURE 7.

Model illustrating our findings on how RACK1 association with FAK is regulated. In adherent serum-starved cells (left panel) RACK1 associates with the IGF-IR. FAK associates with RACK1 and is phosphorylated on Tyr-397, presumably because of integrin ligation. Upon stimulation with IGF-I (right panel), c-Abl activity is enhanced, and RACK1 is phosphorylated on Tyr-52, which regulates and stabilizes the interaction with FAK. FAK then becomes dephosphorylated at Tyr-397, which promotes cell migration. Suppression of RACK1 expression, inhibition of c-Abl kinase activity, or mutation of Tyr-52 are all sufficient to ablate FAK phosphorylation. Thus, the association of FAK with RACK1 at Tyr-52 is essential for activity of FAK.