Sequence requirements for induction of cytolysis by the T cell antigen/Fc receptor zeta chain

The zeta chain of the T cell antigen receptor is a dimeric transmembrane protein with a very short extracellular domain and an extended cytoplasmic tail that triggers T cell effector function when aggregated by extracellular stimuli. We have reduced the active site of zeta to an 18 residue motif that can be appended to the intracellular domain of other transmembrane proteins to endow them with receptor-like activity. The compact size of the motif appears to eliminate zeta mechanisms based on enzymatic activity and suggests that one or at most a few cellular proteins interact with the zeta intracellular domain to initiate signal transduction. Analysis of individual amino acids within the 18 residue element reveals two phylogenetically conserved tyrosines that are absolutely required for activity and other residues that are less essential but contribute to the efficacy of receptor-directed cytolysis.