Mechanisms of focal adhesion kinase regulation.
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. FAK's 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. FAK's involvement in cellular pathways that regulate cell growth and cell movement suggests that it may contribute to the development of cancer or other diseases. FAK's possible involvement in these pathways makes it a potential drug target. In this review we will focus on the developing view how FAK's activity and phosphorylation are regulated within the cell. Specifically, we will address the contribution of integrins and growth factor dependent pathways to FAK's activation. The role of the tyrosine kinase Src in FAK's regulation will be discussed. The contribution of various negative regulators of FAK's phosphorylation on its regulation including phosphatases and proteases will be discussed. Lastly, the emerging role of FAK's amino terminal FERM like domain in FAK's regulation will be explored. FAK's 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.
Cohen
Lee Ann
LA
Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
Guan
Jun-Lin
JL
D000595:Amino Acid Sequence; D000818:Animals; D048708:Cell Growth Processes; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid
D016023:Integrins; D051416:Focal Adhesion Protein-Tyrosine Kinases