CUTTING EDGE - NEGATIVE REGULATION OF HUMAN T-CELL ACTIVATION BY THE RECEPTOR-TYPE PROTEIN-TYROSINE-PHOSPHATASE CD148

T cell activation represents a balance between positive and negative s ignals delivered via distinct cell surface molecules. Many cytoplasmic protein tyrosine phosphatases are involved in regulating cellular res ponses by antagonizing the action of protein tyrosine kinases, CD148 i s a receptor-type protein tyrosine phosphatase expressed by all human mononuclear cells. We have investigated the effect of CD148 on TCR-med iated activation of human T cells. Overexpression of wild-type, but no t a phosphatase deficient, CD148 in Jurkat T cells inhibited TCR-media ted activation, evidenced by reduced expression of the early activatio n Ag CD69, inhibition of tyrosine phosphorylation of many intracellula r proteins including the critical protein tyrosine kinase ZAP-70, and impairment of mitogen-activated protein kinase activation. Taken toget her, these results suggest that CD148 is an important phosphatase invo lved in negatively regulating the proximal signaling events during act ivation of Ag-specific T cells.