Functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of monoblastoid leukemia cells.
A large family of protein tyrosine phosphatases (PTPs) bidirectionally regulate intracellular signaling pathways by reversing agonistic or antagonistic 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-tetradecanoylphorbol-13-acetate, ectopic expression of PTP-U2L in U937 cells enhanced several characteristics of terminally differentiated cells. Most striking 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 the ability to enhance the differentiation but retained the ability to enhance the following apoptosis of the cells to a lesser extent. These data indicate a functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of U937 cells. Since terminally differentiated blood cells often undergo apoptosis, the data also suggest that PTP-U2L might be involved in physiological turnover of hematopoietic cells in vivo.
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan. hseimiya@jfcr.or.jp
H
H
Seimiya
T
T
Tsuruo
D017209:Apoptosis; D002384:Catalysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D007948:Leukemia, Monocytic, Acute / Q000201:enzymology* / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D007527:Isoenzymes; D017027:Protein Tyrosine Phosphatases; D013755:Tetradecanoylphorbol Acetate