GIT1 utilizes a focal adhesion targeting-homology domain to bind paxillin

Robert Schmalzigaug, Marie Line Garron, J. Tyler Roseman, Yanghui Xing, Collin E. Davidson, Stefan Arold, Richard T. Premont*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The GIT proteins, GIT1 and GIT2, are GTPase-activating proteins for the ADP-ribosylation factor family of small GTP-binding proteins, but also serve as adaptors to link signaling proteins to distinct cellular locations. One role for GIT proteins is to link the PIX family of Rho guanine nucleotide exchange factors and their binding partners, the p21-activated protein kinases, to remodeling focal adhesions by interacting with the focal adhesion adaptor protein paxillin. We here identified the C-terminal domain of GIT1 responsible for paxillin binding. Combining structural and mutational analyses, we show that this region folds into an anti-parallel four-helix domain highly reminiscent to the focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Our results suggest that the GIT1 FAT-homology (FAH) domain and FAT bind the paxillin LD4 motif quite similarly. Since only a small fraction of GIT1 is bound to paxillin under normal conditions, regulation of paxillin binding was explored. Although paxillin binding to the FAT domain of FAK is regulated by tyrosine phosphorylation within this domain, we find that tyrosine phosphorylation of the FAH domain GIT1 is not involved in regulating binding to paxillin. Instead, we find that mutations within the FAH domain may alter binding to paxillin that has been phosphorylated within the LD4 motif. Thus, despite apparent structural similarity in their FAT domains, GIT1 and FAK binding to paxillin is differentially regulated.

Original languageEnglish (US)
Pages (from-to)1733-1744
Number of pages12
JournalCellular Signalling
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2007

Keywords

  • Arf GTPase-activating protein
  • Focal adhesion targeting domain
  • GIT1 protein
  • Guanine nucleotide exchange factor
  • PIX protein
  • Paxillin

ASJC Scopus subject areas

  • Cell Biology

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