Interaction of the unique N-terminal region of tyrosine kinase p56 super(lck) with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs

p56 super(lck), a lymphocyte-specific member of the src family of cytoplasmic protein-tyrosine kinases, is associated noncovalently with the cell surface glycoproteins CD4 and CD8, which are expressed on functionally distinct subpopulations of T cells. Using transient co-expression of p56 super(lck) with CD4 or CD8 alpha in COS-7 cells, we show that the unique N-terminal region of p56 super(lck) binds to the membrane-proximal 10 and 28 cytoplasmic residues of CD8 alpha and CD4, respectively. Two cysteine residues in each of the critical sequences in CD4, CD8 alpha , and p56 super(lck) are required for association. Our results suggest a novel role for cysteine-mediated interactions between unrelated proteins and provide a model for the association of other src -like cytoplasmic kinases with transmembrane proteins.