Tac-beta1 inhibits FAK activation and Src signaling

Biochemical and Biophysical Research Communications
A L BerrierS E LaFlamme

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 neces...Continue Reading

References

Sep 1, 1995·The Journal of Cell Biology·M D SchallerJ T Parsons
Mar 8, 1996·The Journal of Biological Chemistry·H KawakatsuJ Yano
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T C HeB Vogelstein
Jan 10, 2002·Frontiers in Bioscience : a Journal and Virtual Library·Patricia Pellicena, W Todd Miller
Jun 29, 2002·Circulation Research·Maria C HeidkampAllen M Samarel
Oct 12, 2002·Journal of Cell Science·Allison L BerrierSusan E LaFlamme
May 14, 2003·The EMBO Journal·Cord Brakebusch, Reinhard Fässler
Oct 31, 2003·Molecular and Cellular Biology·Lee Ann CooperJun-Lin Guan
Nov 1, 2003·Proceedings of the National Academy of Sciences of the United States of America·Elena G Arias-SalgadoSanford J Shattil
Jul 13, 2004·Biochimica Et Biophysica Acta·David D SchlaepferDusko Ilic
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Satyajit K MitraDavid D Schlaepfer
Jul 26, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Peter V Usatyuk, Viswanathan Natarajan
Jun 19, 2007·Cell·Daniel LiethaMichael J Eck
Aug 8, 2007·Journal of Cellular Physiology·Allison L Berrier, Kenneth M Yamada

❮ Previous
Next ❯

Citations

Aug 28, 2010·Tissue Engineering. Part a·Smit J DangariaThomas G H Diekwisch
Mar 25, 2010·Journal of Cell Science·Bethsaida NievesSusan E LaFlamme
Feb 26, 2009·Genes & Development·Kyle R LegateReinhard Fässler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.