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Paxillin Interactions

The paxillin superfamily is composed paxillin (PXN), hydrogen peroxide inducible clone-5 (Hic-5) and leupaxin (LPXN). Paxillin exists as paxillin alpha (PXNα), its mRNA splice variants, paxillin beta (PXNβ) and paxillin gamma (PXNγ) and as paxillin delta (PXNδ) which results from an alternative mRNA translation initiation site. Paxillin is a focal adhesion complex (FAC) associating multidomain adaptor and scaffold molecule that integrates and manages signals from integrins, cell surface receptors (GPCRs) and growth factors to affect cell mobility (chemotaxis) and gene activation. Paxillin interacts with a wide array of molecules involved in managing the cells response to extracellular matrix components, growth factors, cell:cell interactions and chemotatic signals. Paxillin is targeted to focal adhesions through its Lim2/3 domains and interacts with focal adhesion kinase-1 (FAK) via its LD2/4 domains. Paxillin contains a large number of sites for both tyrosine and serine/threonine phosphorylation. The phosphorylation of these sites by a wide variety of growth factor receptor tyrosine kinases (RTK), Src kinases, and serine/threonine kinases such as the MAP-kinases; ERK, JNK, and p38 regulate the binding of specific adaptor molecules that control the initiation and termination of coordinated cell signaling pathways.

The interaction of FAC associated integrins with components of the extracellular matrix (ECM) induces the autophosphorylation of paxillin associated FAK which then binds Src kinase. Bound Src kinase phosphorylates both FAK and paxillin at specific sites. Phosporylated FAK and paxillin function together to manage spaciotemporal contol over guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP) to regulate the activities of the GTPases involved in cytoskeletal and microtubule remodeling. These include the Arf-GTPases; Arf 1 and Arf6 and the RhoGTPases; Rho, Cdc42 and Rac-1. These GTPases regulate the formation of stress fibers (RhoA), filopodia (Cdc42), lamellipodia (Rac-1), and membrane trafficking/actin remodeling (Arfs) that are required to affect cell shape changes and movement.

References:

Brown, M.C. et. al. (2005) Src and FAK kinases cooperate to phosphorylate paxillin kinase linker, stimulate its focal adhesion localization, and regulate cell spreading and protrusiveness. Mol. Biol. Cell. 16, 4316-4328.
Brown, M.C. and Turner, C.E. (2004) Paxillin: adapting to change. Physiol. Rev. 84, 1315-1339.
Clarke, D.M. (2004) Phosphorylation of actopaxin regulates cell spreading and migration. J. Cell Biol. 166, 901-912.

Content for this page is provided by Dennis R. Conrad, Ph.D., a Life Science industry consultant with over 25 years of experience in the formulation and optimization of cell culture media. Dr. Conrad's email address is biomediaexpert@earthlink.net