~ 56”~, a lymphocyte-specific member of the SIC 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 coexpression of~ 56’~” with CD4 or CD8a in COS-7 cells, we show that the unique N-terminal region of p56jCk binds to the membrane-proximal 10 and 28 cytoplasmic residues of CD8a and CD4, respectively. Two cysteine residues in each of the critical sequences in CD4, CD8a, and p561Ck 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.