Integrin receptors facilitate T cell function by mediating adhesive events critical for T cell trafficking and recognition of foreign antigen, including interactions with vascular endothelium, extracellular matrix components, and antigen-presenting cells. Consequently, the functional activity of integrin receptors is acutely regulated by various intracellular signals delivered by other cell surface receptors, resulting in rapid changes in T cell adhesion and migration. This review highlights recent insights into our understanding of the signaling events by which the CD3/T cell receptor complex and chemokine receptors regulate integrin function and T cell migration. These studies highlight novel functions for several signaling molecules, including the tyrosine kinases Itk and ZAP-70, and the adapter protein SLAP-130/Fyb. In addition, analysis of the regulation of integrin function and chemokine-mediated migration has highlighted the critical role that spatial localization of signaling molecules plays in signal transduction, and the importance of the actin cytoskeleton in T cell function.
Bibliographical noteFunding Information:
We thank Drs. G. Koretzky and E. Peterson for critical comments and discussion. Work in the senior author’s laboratory is supported by NIH grants AI31126 and AI38474, and by Department of Defense grant DAMD17-00-1-0348. Jonathan Pribila is supported by American Heart Association predoctoral fellowship 0010139Z. Yoji Shimizu is the Harry Kay Chair of Cancer Research at the University of Minnesota Medical School.
- Signal transduction
- T lymphocyte