Signaling networks regulating β1 integrin-mediated adhesion of T lymphocytes to extracellular matrix

Abstract

Abstract T-cell recognition of foreign antigen and migration to specificanatomic sites in vivo involves transient adhesive contacts betweenβ1 integrins expressed on T cells and cell surface proteins orextracellular-matrix components. Engagement of the CD3-T-cell receptor(CD3-TCR) complex initiates a complex signaling cascade involvingcoordinated regulation and recruitment of tyrosine and lipid kinases tospecific regions or microdomains in the plasma membrane. Althoughconsiderable attention has been focused on the signaling events bywhich the CD3-TCR complex regulates transcriptional events in thenucleus, CD3-TCR signaling also rapidly enhances integrin-mediatedadhesion without increasing surface expression of integrins. Recentstudies suggest that CD3-TCR signaling to β1 integrins involvescoordinated recruitment and activation of the Tec family tyrosinekinase Itk by src family tyrosine kinases and phosphatidylinositol3-kinase. These signaling events that regulate integrin-mediated T-celladhesion share both common and distinct features with the signalingpathways regulating interleukin-2 gene transcription.