Multiple paxillin binding sites regulate FAK function

Danielle M Scheswohl¹ , Jessica R Harrell¹ , Zenon Rajfur¹ , Guanghua Gao² , Sharon L Campbell²^,3 and Michael D Schaller¹^,3

¹Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA

²Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA

³Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA

author email corresponding author email

Journal of Molecular Signaling 2008, 3:1doi:10.1186/1750-2187-3-1


Published:	2 January 2008

Abstract

Background

FAK localization to focal adhesions is essential for its activation and function. Localization of FAK is mediated through the C-terminal focal adhesion targeting (FAT) domain. Recent structural analyses have revealed two paxillin-binding sites in the FAT domain of FAK. To define the role of paxillin binding to each site on FAK, point mutations have been engineered to specifically disrupt paxillin binding to each docking site on the FAT domain of FAK individually or in combination.

Results

These mutants have been characterized and reveal an important role for paxillin binding in FAK subcellular localization and signaling. One paxillin-binding site (comprised of α-helices 1 and 4 of the FAT domain) plays a more prominent role in localization than the other. Mutation of either paxillin-binding site has similar effects on FAK activation and downstream signaling. However, the sites aren't strictly redundant as each mutant exhibits phosphorylation/signaling defects distinct from wild type FAK and a mutant completely defective for paxillin binding.

Conclusion

The studies demonstrate that the two paxillin-binding sites of FAK are not redundant and that both sites are required for FAK function.