DEFECTIVE EXPRESSION OF HEMATOPOIETIC-CELL PROTEIN-TYROSINE-PHOSPHATASE (HCP) IN LYMPHOID-CELLS BLOCKS FAS-MEDIATED APOPTOSIS

Protein tyrosine dephosphorylation after Fas crosslinking occurred in Fas apoptosis-sensitive CEM-6 cells but not in Pas apoptosis-resistant MOLT-4 cells, and apoptosis in the CEM-6 cells could be inhibited by the protein tyrosine phosphatase inhibitor, pervanadate. The time cour se and level of dephosphorylation were correlated with increased hemat opoietic cell protein tyrosine phosphatase (HCP) activity, but not wit h the activity of two other tyrosine phosphatases. The level of expres sion of HCP was correlated with Fas apoptosis function in eleven human and murine Fas-positive lymphoid cell lines. Expression of recombinan t HCP in the MOLT-4 cell line converted this Fas apoptosis-resistant c ell line to Pas apoptosis sensitive. HOP-mutant me(v)/me(v) mice exhib ited increased expression of Fas but decreased Fas-mediated apoptosis function in lymphoid organs after anti-mouse Fas antibody treatment in vivo. Thus, HCP-mediated protein dephosphorylation is involved in the delivery of the Pas apoptosis signal in lymphoid cells.