Figure 2.

Given here is the assumed chain of force transduction from the F-actin of the cytoskeleton, through the activated β-integrin binding to ligands of the deformable ECM. The FERM domain of FAK is associated with the cell membrane, near the integrin-talin head assembly, whereas the FAT domain is associated with actin through its binding to paxillin (30). The pulling force is transmitted through this chain to the FERM-kinase physical bond. In the closed state [c] the kinase domain is inactive and the whole FAK protein is in its native low-energy state. Once the physical bond holding the FERM domain and the kinase together is broken, the protein adopts the open conformation [o]. In the open state, first the Tyr³⁹⁷ site spontaneously phosphorylates, which in turn allows binding of Src and further phosphorylation of the kinase—turning it into the active state [a] (see (45, 70, 71)). To see this figure in color, go online.