Signal transduction events regulating integrin function and T cell migration: new functions and complexity.
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.
Pribila
Jonathan T
JT
Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Shimizu
Yoji
Y
D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D003599:Cytoskeleton / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000276:immunology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016023:Integrins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019707:Receptors, Chemokine