FAK

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Focal Adhesion Kinase (FAK) is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes.^[1]

FAK is a 125 Kd protein that is recruited as a participant in focal adhesion dynamics between cells and has a role in motility and cell survival. Focal adhesion kinase (FAK) is a 125 kDa, highly conserved, non-receptor tyrosine kinase originally identified as a substrate for the oncogene protein tyrosine kinase v-src {Guan, 1992 9 /id;Kanner, 1990 8 /id}. This cytosolic kinase has been implicated in diverse cellular roles including cell locomotion, mitogen response and cell survival. FAK is typically located at structures known as focal adhesions, these are multi-protein structures that link the extracellular matrix (ECM) to the cytoplasmic cytoskeleton. Additional components of focal adhesions include actin, -actinin, filamin, vinculin, talin, paxillin and tensin {Chrzanowska-Wodnicka, 1996 11 /id}.

FAK is phosphorylated in response to integrin engagement, growth factor stimulation and the action of mitogenic neuropeptides {Abedi, 1997 12 /id;Zachary, 1992 13 /id}. Integrin receptors are heterodimeric transmembrane glycoproteins that cluster upon ECM engagement leading to FAK phosphorylation and recruitment to focal adhesions {Burridge, 1988 15 /id;Burridge, 1992 16 /id}.

Focal adhesion kinase has a number of defined regions. A carboxy-terminal region of one hundred and fifty-nine amino acids, the focal adhesion targeting domain (FAT), has been shown to be responsible for targeting FAK to focal adhesions {Hildebrand, 1993 17 /id}. Paxillin, a focal adhesion adaptor protein binds to FAK at a carboxy-terminal domain that overlaps the FAT domain {Hildebrand, 1995 20 /id}.

The function of the amino-terminal domain is less clear, but it has been shown to interact with the beta-1 integrin subunit in vitro and is thought to be involved in the transduction of signals from ECM-integrin clusters{Schaller, 1995 21 /id}. However, a recent study has called into question the importance of this interaction and suggested that interaction with the cytoplasmic region of the beta-3 integrin subunit is important {Tahiliani, 1997 22 /id}.

The amino-terminal domains of FAK share a significant sequence similarity with the band 4.1 domain first identified in erythrocytes. This 4.1 band domain binds to the cytoplasmic region of transmembrane proteins including glycophorin C, actin and spectrin {Girault, 1999 23 /id}. This suggests that the amino-terminal region of FAK may have a role in anchoring the cytoskeleton, the exact nature of this role has not been clarified as yet. Between the amino and the carboxy regions lies the catalytic domain. Phosphorylation of the activation loop within this kinase domain is important for the kinase activity of FAK {Calalb, 1995 24 /id}.

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