The focal adhesion protein paxillin is necessary for the activation of focal adhesion kinase

Focal adhesions are a multi-protein complex where integrins contact the extracellular matrix. The focal adhesion protein complex generates signals from the plasma membrane and transmits these signals to the interior of the cell. Paxillin is a focal adhesion associated adaptor protein that has been implicated in signaling from the plasma membrane. Paxillin binds to many other signaling molecules such as FAK (Focal Adhesion Kinase) and Src families of non-receptor tyrosine kinases, structural proteins like vinculin, adaptor proteins CRK and p130CAS, and ARF-GAP proteins p95pkl and PAG3.; Paxillin is composed of five conserved protein binding domains in the amino terminus called LID motifs; that function as protein-protein interaction motifs for paxillin binding partners.{09}The carboxyl terminus of paxillin is composed of four double zinc finger LIM domains; that are responsible for localization of paxillin within the cell as well as protein binding. Paxillin is a member of a family of proteins including hic5 and leupaxin that all share many binding partners as well as structural similarities.; Although paxillin binds to a large assortment of proteins which are involved in many diverse signaling pathways, little definitive information is known about paxillin's exact role in focal adhesion signaling. Paxillin null mouse embryonic stem cells were created by targeted gene disruption. The paxillin null cells do not express paxillin or the related family member hic5. The paxillin null cells show a defect in the rate of cell spreading on the extracellular matrix proteins fibronectin and laminin. These cells also show a marked decrease in the tyrosine phosphorylation of FAK. These phenotypes can be corrected by expression of exogenous paxillin. Extensive mutational analysis of paxillin implicate that the LIM3 domain of paxillin is required to support the tyrosine phosphorylation of FAK.