| http://purl.uniprot.org/citations/19423701 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19423701 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19423701 | http://www.w3.org/2000/01/rdf-schema#comment | "Focal Adhesion Kinase (FAK) activity is controlled by growth factors and adhesion signals in tumor cells. The scaffolding protein RACK1 (receptor for activated C kinases) integrates insulin-like growth factor I (IGF-I) and integrin signaling, but whether RACK1 is required for FAK function is unknown. Here we show that association of FAK with RACK1 is required for both FAK phosphorylation and dephosphorylation in response to IGF-I. Suppression of RACK1 by small interfering RNA ablates FAK phosphorylation and reduces cell adhesion, cell spreading, and clonogenic growth. Peptide array and mutagenesis studies localize the FAK binding interface to blades I-III of the RACK1 beta-propeller and specifically identify a set of basic and hydrophobic amino acids (Arg-47, Tyr-52, Arg-57, Arg-60, Phe-65, Lys-127, and Lys-130) as key determinants for association with FAK. Mutation of tyrosine 52 alone is sufficient to disrupt interaction of RACK1 with FAK in cells where endogenous RACK1 is suppressed by small interfering RNA. Cells expressing a Y52F mutant RACK1 are impaired in adhesion, growth, and foci formation. Comparative analyses of homology models and crystal structures for RACK1 orthologues suggest a role for Tyr-52 as a site for phosphorylation that induces conformational change in RACK1, switching the protein into a FAK binding state. Tyrosine 52 is further shown to be phosphorylated by c-Abl kinase, and the c-Abl inhibitor STI571 disrupts FAK interaction with RACK1. We conclude that FAK association with RACK1 is regulated by phosphorylation of Tyr-52. Our data reveal a novel mechanism whereby IGF-I and c-Abl control RACK1 association with FAK to facilitate adhesion signaling."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.017640"xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.017640"xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Barrett R."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Barrett R."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Houslay M.D."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Houslay M.D."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Baillie G.S."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Baillie G.S."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Adams D.R."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Adams D.R."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "O'Connor R."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "O'Connor R."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Buckley D.A."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Buckley D.A."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Kiely P.A."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/author | "Kiely P.A."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/pages | "20263-20274"xsd:string |
| http://purl.uniprot.org/citations/19423701 | http://purl.uniprot.org/core/pages | "20263-20274"xsd:string |