Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56^lck

Abstract

THE CD4 T-cell surface antigen is an integral membrane gly-coprotein of relative molecular mass 55,000 which binds class II major histocompatibility complex (MHC) molecules expressed on antigen presenting cells (APCs). It is thought to stabilize physical interactions between T cells and APCs (for a review, see ref. 1). Evidence is accumulating that suggests that CD4 can transduce an independent signal during T-cell activation^2–4. It has recently been shown that CD4 expressed on human^5,6 and murine⁶ T cells is physically associated with the Src-related tyrosine protein kinase p56^lck (refs 7, 8). These results indicate that CD4 can function as a signal transducer and suggest that tyrosine phosphorylation events may be important in CD4-mediated signalling. Here, we present evidence that cross-linking of the CD4 receptor induces a rapid increase in the tyrosine-specific protein kinase activity of p56^lck and is associated with the rapid phosphorylation of one of the subunits (ζ) of the T-cell receptor complex on tyrosine residues. These data provide direct evidence for a specific CD4 signal transduction pathway that is mediated through p56^lck and suggest that some of the tyrosine phosphorylation events detected during antigen-mediated T-cell activation may result from signalling through this surface molecule.