Tac-beta1 inhibits FAK activation and Src signaling.
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.
Berrier
Allison L
AL
Center for Cell Biology and Cancer Research, Albany Medical Center, 47 New Scotland Avenue, Albany, NY 12208, USA.
Jones
Christopher W
CW
LaFlamme
Susan E
SE
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*
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