Characterization of a focal adhesion protein, Hic-5, that shares extensivehomotogy with paxillin

Paxillin is a focal adhesion scaffolding protein which was originally ident ified as a substrate of the oncogenic tyrosine kinase, v-src, Paxillin has been proposed to be involved in regulation of focal adhesion dynamics. Two alternatively spliced mouse paxillin cDNAs were cloned and in the process, a paxillin-related protein, Hic-5, was also identified. Cloning and charact erization of Hic-5 indicates that this protein shares extensive homology wi th paxillin, Although Hic-5 was originally characterized as a TGF-beta-indu cible gene and proposed to be a transcription factor involved in senescence , the studies here demonstrate that Hic-5 is localized to focal adhesion in REF52 cells and can interact,vith the focal adhesion proteins, Fak, Frnk, and vinculin, In addition, like paxillin, Hic-5 can bind to a negative regu lator of Src PTKs, csk but does not bind to the adaptor protein Crk, Like p axillin, localization of this protein to focal adhesions is mediated primar ily by the LIM domains; however, sequences outside the LIM domains also pla y a minor role in focal adhesion targeting. These results suggest that Hic- 5 like paxillin could be involved in regulation of focal adhesion dynamics and raise the possibility that Hic-5 and paxillin could have overlapping or opposing functions in the overall regulation of cell growth and differenti ation.