ACTIVATION-DEPENDENT UBIQUITINATION OF A T-CELL ANTIGEN RECEPTOR SUBUNIT ON MULTIPLE INTRACELLULAR LYSINES

The T cell antigen receptor zeta chain and other T cell antigen recept or components are ubiquitinated on receptor occupancy. A systematic mu tagenesis of the zeta subunit was undertaken to determine the sites of ubiquitination. Ubiquitination was found to occur in the cytoplasmic domain of zeta with multiple lysines serving as sites for mono- and po lyubiquitination. The mutation of all potential sites of ubiquitinatio n did not inhibit receptor tyrosine phosphorylation or the ubiquitinat ion of other T cell antigen receptor subunits. Lysines introduced into nonnative positions in the zeta molecule were also able to serve as s ites for ubiquitination. These findings demonstrate that once a T cell antigen receptor is targeted for ubiquitination, there is little spec ificity with regard to the lysine residues that are modified.