Title: Mechanisms of Focal Adhesion Kinase Regulation
Volume: 5
Issue: 8
Author(s): Lee A. Cohen and Jun-Lin Guan
Affiliation:
Keywords:
cellular signal, phosphorylation, NXXY motifs, c-Src, GTPases RhoA, Phosphatases
Abstract: Focal adhesion kinase (FAK) is a tyrosine kinase whose phosphorylation state and activity is tightly linked to cell adhesion to the extracellular matrix through integrin receptors. FAKs regulation by adhesion places it in a key position to be able to influence cellular events that are either dependent on cell adhesion like cell proliferation and survival, or that require modulation of cell adhesion like cell migration. FAKs involvement in cellular pathways that regulate cell growth and cell movement suggests that it may contribute to the development of cancer or other diseases. FAKs possible involvement in these pathways makes it a potential drug target. In this review we will focus on the developing view how FAKs activity and phosphorylation are regulated within the cell. Specifically, we will address the contribution of integrins and growth factor dependent pathways to FAKs activation. The role of the tyrosine kinase Src in FAKs regulation will be discussed. The contribution of various negative regulators of FAKs phosphorylation on its regulation including phosphatases and proteases will be discussed. Lastly, the emerging role of FAKs amino terminal FERM like domain in FAKs regulation will be explored. FAKs function within a cell are tightly linked to its phosphorylation state, thus understanding its normal regulation in the cell will provide important insight into drug development by highlighting novel regulatory mechanisms within FAK that potentially may be exploited.
