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 course and level of dephosphorylation were correlated with increased hematopoietic cell protein tyrosine phosphatase (HCP) activity, but not with the activity of two other tyrosine phosphatases. The level of expression of HCP was correlated with Fas apoptosis function in eleven human and murine Fas-positive lymphoid cell lines. Expression of recombinant HCP in the MOLT-4 cell line converted this Fas apoptosis-resistant cell line to Pas apoptosis sensitive. HOP-mutant me(v)/me(v) mice exhibited 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.