FUNCTIONAL INVOLVEMENT OF PTP-U2L IN APOPTOSIS SUBSEQUENT TO TERMINALDIFFERENTIATION OF MONOBLASTOID LEUKEMIA-CELLS

A large family of protein tyrosine phosphatases (PTPs) bidirectionally regulate intracellular signaling pathways by reversing agonistic or a ntagonistic phosphorylation events derived from the action of protein tyrosine kinases. Receptor-like PTP PTP-U2 is expressed during phorbol ester-induced differentiation of monoblastoid leukemia U937 cells. We found that the shorter isoform, PTP-U2S, was expressed at an earlier phase in the course of differentiation and the longer isoform, PTP-U2L , was induced at a later phase. In the presence of 12-O-tetradecanoylp horbol-13-acetate, ectopic expression of PTP-U2L in U937 cells enhance d several characteristics of terminally differentiated cells. Most str iking was that PTP-U2L enhanced apoptosis of the differentiated cells, which was only partially inhibited by caspase inhibitor Z-Asp-CH2-DCB . The catalytically inactive mutant PTP-U2L(C --> S) still retained th e ability to enhance the differentiation but retained the ability to e nhance the following apoptosis of the cells to a lesser extent. These data indicate a functional involvement of PTP-U2L in apoptosis subsequ ent to terminal differentiation of U937 cells. Since terminally differ entiated blood cells often undergo apoptosis, the data also suggest th at PTP-U2L might be involved in physiological turnover of hematopoieti c cells in vivo.