Focal Adhesion Kinase: a regulator of focal adhesion dynamics and cell movement

Abstract

Engagement of integrin receptors with extracellular ligands gives rise to the formation of complex multiprotein structures that link the ECM to the cytoplasmic actin cytoskeleton. These adhesive complexes are dynamic, often heterogeneous structures, varying in size and organization. In motile cells, sites of adhesion within ®lopodia and lamellipodia are relatively small and transient and are referred to as`focal complexes,' whereas adhesions underlying the body of the cell and localized to the ends of actin stress ®bers are referred to as`focal adhesions'. Signal transduction through focal complexes and focal adhesions has been implicated in the regulation of a number of key cellular processes, including growth factor induced mitogenic signals, cell survival and cell locomotion. The formation and remodeling of focal contacts is a dynamic process under the regulation of protein tyrosine kinases and small GTPases of the Rho family. In this review, we consider the role of the focal complex associated protein tyrosine kinase, Focal Adhesion Kinase (FAK), in the regulation of cell movement with the emphasis on how FAK regulates the¯ow of signals from the ECM to the actin cytoskeleton. Oncogene (2000) 19, 5606 ± 5613.

Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective

“…Regardless of the precise upstream components, cofilin phosphorylation results in reduced actin filament disassembly and thus stabilization of stress fibers. Stress fibers are therefore available to be anchored to mature focal adhesions [2,70] and can transmit contractile forces exerted by the actomyosin machinery to the extracellular matrix.…”

Expression levels of the focal adhesion-associated proteins paxillin and p130CAS in canine and feline mammary tumors

“…Even though both paxillin and p130 CAS have been shown to have a regulatory role in focal adhesion dynamics and cell movement [16], whether and how the two protein signaling pathways, which have been studied in cultured cells, relate to signaling in the complex organization of individual tissues has not yet been established.…”

Activation of FAK and Src are receptor-proximal events required for netrin signaling

“…FAK is activated by integrins and other extracellular signals. FAK activation stimulates multiple cellular signal transduction events leading to cell adhesion, motility and cell morphological changes [15][16][17] . In response to integrin stimulation, FAK binds to Src and stimulates Src activity.…”