ACTIVATION OF THE LCK TYROSINE KINASE TARGETS CELL-SURFACE T-CELL ANTIGEN RECEPTORS FOR LYSOSOMAL DEGRADATION

The mechanism by which TCR expression is regulated was explored by exp ressing a constitutively active form of the tyrosine kinase Lck (Lck(5 05F)) in T cells. Expression of Lck(505F) down-regulated TCR levels, a n effect that was even more pronounced in CD45(-) T cells, in which th e activity of this tyrosine kinase is further enhanced. Cells expressi ng Lck(505F) synthesized all TCR subunits, but lysosomal degradation o f assembled receptors was enhanced. TCRs were rapidly internalized and degraded after removal of a tyrosine kinase inhibitor that had permit ted cell surface expression. Finally, TCR levels on thymocytes were in creased by an Lck inhibitor, and activation- but not phorbol ester-ind uced internalization of TCRs on Jurkat cells was prevented by inhibiti on or loss of Lck. These studies identify a regulated nonreceptor tyro sine kinase-mediated pathway for targeting cell surface receptors for lysosomal degradation.