H. Seimiya et T. Tsuruo, FUNCTIONAL INVOLVEMENT OF PTP-U2L IN APOPTOSIS SUBSEQUENT TO TERMINALDIFFERENTIATION OF MONOBLASTOID LEUKEMIA-CELLS, The Journal of biological chemistry, 273(33), 1998, pp. 21187-21193
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.