title: Tac-beta1 inhibits FAK activation and Src signaling.
abstract: The binding of integrins to extracellular matrix triggers signals that promote cell spreading. We previously demonstrated that expression of the integrin beta1 cytoplasmic domain in the context of a chimeric transmembrane receptor with the Tac subunit of the interleukin-2 receptor (Tac-beta1) inhibits cell spreading. To study the mechanism whereby Tac-beta1 inhibits cell spreading, we examined the effect of Tac-beta1 on early signaling events following integrin engagement namely FAK and Src signaling. We infected primary fibroblasts with adenoviruses expressing Tac or Tac-beta1 and found that Tac-beta1 prevented FAK activation by inhibiting the phosphorylation of FAK at Tyr-397. In contrast, Src activation was maintained, as phosphorylation of Src at Tyr-419 and Tyr-530 were not responsive to expression of Tac-beta1. Importantly, adhesion-induced tyrosine phosphorylation of the Src substrates p130Cas and paxillin was inhibited, indicating that Src signaling was blocked by Tac-beta1. These Src-dependent signaling events were found to require FAK signaling. Our results suggest that Tac-beta1 inhibits cell spreading, at least in part, by preventing the phosphorylation of FAK at Tyr-397 and the assembly of signaling complexes necessary for phosphorylation of p130Cas and other downstream effectors.
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical Center, 47 New Scotland Avenue, Albany, NY 12208, USA.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Berrier
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Jones
authors.forename: Susan E
authors.initials: SE
authors.lastname: LaFlamme
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D051419:Paxillin / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000737:chemistry* / Q000235:genetics; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D050719:Crk-Associated Substrate Protein; D051419:Paxillin; D021122:Protein Subunits; D015375:Receptors, Interleukin-2; D019000:Phosphotyrosine; D051417:Focal Adhesion Kinase 1; D019061:src-Family Kinases