Regulation of integrin function by T cell activation: points of convergence and divergence.
Lymphocyte adhesiveness is dynamically regulated in response to conditions in the extracellular environment. One mechanism of regulation of integrin adhesion receptors involves a rapid, but transient, increase in integrin function upon T lymphocyte activation. These integrin activating signals can be initiated either via ligation of Ig superfamily members that are coupled to tyrosine kinase cascades, such as the CD3/T cell receptor, CD2, and CD28, or by G protein-coupled receptors for chemokines. Analysis of integrin activation induced by CD3/TCR, CD2 and CD28 suggests a critical role for phosphoinositide 3-OH kinase (PI 3-K). This review summarizes recent insights into PI 3-K-dependent regulation of integrin function in leukocytes, including the mechanisms by which these receptors are coupled to PI 3-K, and potential downstream effectors of PI 3-K that regulate integrin-mediated adhesion in leukocytes.
Zell
T
T
Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, USA.
Kivens
W J
WJ
Kellermann
S A
SA
Shimizu
Y
Y
D000818:Animals; D018801:CD2 Antigens / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D002448:Cell Adhesion; D006801:Humans; D016023:Integrins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D015854:Up-Regulation
D018801:CD2 Antigens; D018106:CD28 Antigens; D016023:Integrins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019869:Phosphatidylinositol 3-Kinases