The T cell receptor z subunit plays crucial roles in signal transduction and in receptor assembly. Zeta is limiting in receptor assembly in T cell hybridomas, is required for conferring competency for the receptor to be transported from the golgi apparatus to the cell surface and is a substrate for a receptor activated protein tyrosine kinase. The structure of the z subunit deduced from cDNA cloning reveals a potential nucleotide binding domain as well as 6 intracellular tyrosines they may serve as substrates for a tyrosine kinase. A model system for studying the role of zeta exists in the zeta negative hybridoma variant MA5.8 where transfection with zeta results in the restoration of cell surface receptor expression. In order to further evaluate structure-function relationships in this system we have undertaken site-specific mutagenesis of specific residues contained within zeta. Preliminary results suggest that mutation of intracellular tyrosines results in a marked diminution of all tyrosine phosphorylation.
