Focal adhesion kinase functions as a receptor-proximal signaling componentrequired for directed cell migration

In performing host-defense functions, cells of the immune system become act ivated by soluble chemokine signals and must migrate through endothelial ce ll or solid tissue barriers to reach sites of inflammation or infection. Re gulated adhesive interactions of immune cells with endothelium, extracellul ar matrix components, and cells of solid organs are critical control points of the overall immune response. Both the soluble chemokine and cell adhesi on receptor-mediated migration signals must converge on common intracellula r targets to engage the cell migration machinery. In this article, we focus on the role of focal adhesion kinase (FAK) and its homolog Pyk2 as cytopla smic mediators of motility events in multiple cell types. We introduce the overall domain structure of the FAK and Pyk2 nonreceptor protein tyrosine k inases (PTKs), highlight some of the signals that activate these PTKs, and detail the molecules that functionally interact and signal transduction pat hways that may mediate cell migration responses. Emphasis is placed on the knowledge gained from studies using FAK-null cells as a model system to dec ipher the role of this PTK in promoting cell motility.