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PMID: 15169899 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

FERM domain interaction promotes FAK signaling.

Molecular and cellular biology ·Vol. 24 ·No. 12 ·2004-06-00 ·Pages 5353-68

Dunty JM, Gabarra-Niecko V, King ML, Ceccarelli DF, Eck MJ, Schaller MD

Abstract

From the results of deletion analyses, the FERM domain of FAK has been proposed to inhibit enzymatic activity and repress FAK signaling. We have identified a sequence in the FERM domain that is important for FAK signaling in vivo. Point mutations in this sequence had little effect upon catalytic activity in vitro. However, the mutant exhibits reduced tyrosine phosphorylation and dramatically reduced Src family kinase binding. Further, the abilities of the mutant to transduce biochemical signals and to promote cell migration were severely impaired. The results implicate a FERM domain interaction in cell adhesion-dependent activation of FAK and downstream signaling. We also show that the purified FERM domain of FAK interacts with full-length FAK in vitro, and mutation of this sequence disrupts the interaction. These findings are discussed in the context of models of FAK regulation by its FERM domain.

MeSH Terms
Animals Binding Sites/genetics Cell Line Cells, Cultured Chick Embryo Focal Adhesion Kinase 1 Focal Adhesion Kinase 2 Focal Adhesion Protein-Tyrosine Kinases Humans In Vitro Techniques Models, Molecular Mutagenesis, Site-Directed Phosphorylation Protein Conformation Protein Structure, Tertiary Protein-Tyrosine Kinases/chemistry,genetics,metabolism Rats Recombinant Fusion Proteins/chemistry,genetics,metabolism Signal Transduction Tyrosine/chemistry src-Family Kinases/metabolism
Chemicals
Recombinant Fusion Proteins Tyrosine Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Kinase 2 Focal Adhesion Protein-Tyrosine Kinases PTK2 protein, human Ptk2 protein, rat Ptk2b protein, rat src-Family Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Dunty Jill M
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, 27599, USA.
Gabarra-Niecko Veronica
King Michelle L
Ceccarelli Derek F J
Eck Michael J
Schaller Michael D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.12.5353-5368.2004
Published
2004-06-00
Pages
5353-68
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC419890
Subset
IM
Grants
NCI NIH HHS · R01 CA090901 · United States
NCI NIH HHS · CA90901 · United States
External Links
PubMed source DOI: 10.1128/MCB.24.12.5353-5368.2004 PMC Full Text View journal details
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