Signaling networks regulating beta1 integrin-mediated adhesion of T lymphocytes to extracellular matrix.
T-cell recognition of foreign antigen and migration to specific anatomic sites in vivo involves transient adhesive contacts between beta1 integrins expressed on T cells and cell surface proteins or extracellular-matrix components. Engagement of the CD3-T-cell receptor (CD3-TCR) complex initiates a complex signaling cascade involving coordinated regulation and recruitment of tyrosine and lipid kinases to specific regions or microdomains in the plasma membrane. Although considerable attention has been focused on the signaling events by which the CD3-TCR complex regulates transcriptional events in the nucleus, CD3-TCR signaling also rapidly enhances integrin-mediated adhesion without increasing surface expression of integrins. Recent studies suggest that CD3-TCR signaling to beta1 integrins involves coordinated recruitment and activation of the Tec family tyrosine kinase Itk by src family tyrosine kinases and phosphatidylinositol 3-kinase. These signaling events that regulate integrin-mediated T-cell adhesion share both common and distinct features with the signaling pathways regulating interleukin-2 gene transcription.
Woods
M L
ML
Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Shimizu
Y
Y
D000199:Actins / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D021962:Membrane Microdomains / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D014158:Transcription, Genetic; D051746:ZAP-70 Protein-Tyrosine Kinase; D019061:src-Family Kinases / Q000502:physiology
D000199:Actins; D019012:Integrin beta1; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019869:Phosphatidylinositol 3-Kinases; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C080813:emt protein-tyrosine kinase; D019061:src-Family Kinases