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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of monoblastoid leukemia cells

H Seimiya1, T Tsuruo

  • 1Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan. hseimiya@jfcr.or.jp

The Journal of Biological Chemistry
|August 8, 1998
PubMed

Insights

Protein tyrosine phosphatases (PTPs) regulate cell signaling. The PTP-U2L isoform enhances terminal differentiation and subsequent apoptosis in leukemia cells, suggesting a role in hematopoietic cell turnover.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Protein tyrosine phosphatases (PTPs) are crucial regulators of intracellular signaling pathways, counteracting protein tyrosine kinases.
  • Receptor-like PTP PTP-U2 is involved in the differentiation of U937 leukemia cells induced by phorbol ester.

Purpose of the Study:

  • To investigate the differential expression and function of PTP-U2 isoforms during U937 cell differentiation.
  • To determine the role of the longer isoform, PTP-U2L, in terminal differentiation and subsequent apoptosis.

Main Methods:

  • Analysis of PTP-U2 isoform expression during phorbol ester-induced differentiation of U937 cells.
  • Ectopic expression of PTP-U2L in U937 cells and assessment of differentiation markers.
  • Evaluation of apoptosis induction in PTP-U2L expressing cells, including experiments with a catalytically inactive mutant.

Main Results:

  • The shorter PTP-U2S isoform was expressed early in differentiation, while the longer PTP-U2L isoform was induced later.
  • Ectopic expression of PTP-U2L enhanced characteristics of terminally differentiated U937 cells.
  • PTP-U2L significantly promoted apoptosis in differentiated cells, with its catalytically inactive mutant showing a reduced effect on apoptosis but not differentiation.

Conclusions:

  • PTP-U2L plays a functional role in promoting apoptosis following terminal differentiation of U937 cells.
  • The findings suggest a potential role for PTP-U2L in the physiological turnover of hematopoietic cells in vivo.

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