Inhibition of ATRA-induced myeloid differentiation in acute promyelocytic leukemia by a new protein tyrosine phosphatase inhibitor, 3,4-dephostatin

J Exp Clin Cancer Res. 2000 Sep;19(3):363-6.

Abstract

We previously reported that the expression and the activity of SHP-1, a non-transmembrane protein tyrosine phosphatase (PTPase) increased during myeloid differentiation of an acute promyelocytic leukemia cell line (HT93) induced by all-trans retinoic acid (ATRA). To examine whether inhibition of SHP-1 activity attenuates myeloid differentiation, we used a new PTPase inhibitor, 3,4-dephostatin, and studied its effect on myeloid differentiation. Suppressive effects on immunoprecipitated SHP-1 phosphatase activity and myeloid cell differentiation were detected. These results suggest that SHP-1 is a substrate for 3,4-dephostatin, and that SHP-1 PTPase activity is closely related to myeloid differentiation.

MeSH terms

  • Cell Differentiation / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Regulation, Enzymologic
  • Granulocytes / enzymology
  • Humans
  • Hydroquinones / pharmacology*
  • Intracellular Signaling Peptides and Proteins
  • Leukemia, Promyelocytic, Acute / enzymology
  • Leukemia, Promyelocytic, Acute / pathology*
  • Macrophage-1 Antigen / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Protein Tyrosine Phosphatases / metabolism
  • Tretinoin / antagonists & inhibitors*
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured

Substances

  • Enzyme Inhibitors
  • Hydroquinones
  • Intracellular Signaling Peptides and Proteins
  • Macrophage-1 Antigen
  • dephostatin
  • Tretinoin
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases