SH2- and SH3-mediated interactions between focal adhesion kinase and Src. J Biol Chem 1998 Jan 02;273(1):577-83
Date
02/07/1998Pubmed ID
9417118DOI
10.1074/jbc.273.1.577Scopus ID
2-s2.0-0031962265 (requires institutional sign-in at Scopus site) 215 CitationsAbstract
Intramolecular SH2 and SH3 interactions mediate enzymatic repression of the Src kinases. One mechanism of activation is disruption of these interactions by the formation of higher affinity SH2 and SH3 interactions with specific ligands. We show that a consensus Src SH3-binding site residing upstream of the Src SH2-binding site in FAK can function as a ligand for the Src SH3 domain. Surface plasmon resonance experiments indicate that a FAK peptide containing both the Src SH2- and SH3-binding sites exhibits increased affinity for Src. Furthermore, the presence of both sites in vitro more potently activates c-Src. A FAK mutant (FAKPro-2) with substitutions destroying the SH3-binding site shows reduced binding to Src in vivo. This mutation also reduces Src-dependent tyrosine phosphorylation on the mutant itself and downstream substrates, such as paxillin. These observations suggest that an SH3-mediated interaction between Src-like kinases and FAK may be important for complex formation and downstream signaling in vivo.
Author List
Thomas JW, Ellis B, Boerner RJ, Knight WB, White GC 2nd, Schaller MDAuthor
Gilbert C. White MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Cell Adhesion Molecules
Chick Embryo
Focal Adhesion Protein-Tyrosine Kinases
Molecular Sequence Data
Mutagenesis, Site-Directed
Phosphorylation
Protein Binding
Protein-Tyrosine Kinases
Proto-Oncogene Proteins pp60(c-src)
Tyrosine
src Homology Domains
