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pp75: A Novel Tyrosine Phosphorylated Protein that Heralds Differentiation of HL-60 Cells

  • Ilana Bushkin
  • Jesse Roth
  • Daphna Heffetz
  • Yehiel Zick
Conference paper
Part of the NATO ASI Series book series (volume 56)

Abstract

The promyelocytic (HL-60) leukemia cells are an excellent model system to study cellular differentiation since they undergo morphological changes in response to various differentiation agents which result in a phenotype with the characteristics of a monocyte/macrophage or a granulocyte (Collins, 1987). Alterations in protein tyrosine phosphorylation were implicated as playing an important role in the induction and maintenance of the differentiated phenotype of HL-60 cells (Frank and Sartorelli, 1988) as several specific oncogene products which possess protein tyrosine kinase (PTK) activity are expressed during early stages of myeloid differentiation (Sariban et al. 1985; Gee et al. 1986; Yu and Glazer, 1987). Hence, Potential substrates for these PTKs could play an important role in regulating the differentiation process. To observe changes in phosphotyrosine metabolism at the substrates level, HL-60 cells were treated with a combination of H2O2 and vanadate to inhibit the intracellular protein tyrosine phosphatase (PTPase) activity (Heffetz et al. 1990). Such treatment enabled us to enhance markedly protein tyrosine phosphorylation and detect a novel 75 kDa protein that undergoes enhanced tyrosine phosphorylation during early stages of differentiation of these cells.

Keywords

Tyrosine Phosphorylation Insulin Receptor Kinase Activity Enhance Tyrosine Phosphorylation Intracellular Protein Tyrosine Rapid Tyrosine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Bushkin I, Zick Y (1990) Alterations in insulin receptor kinase activity during differentiation of HL-60 cells. Biochem Biqphys Res Comnun 172: 676–682CrossRefGoogle Scholar
  2. Chaplinski TJ, Niedel JE (1982) Cyclic nucleotide-induced maturation of human promyelocytic leukemia cells. J Clin Invest 70: 953–964PubMedCrossRefGoogle Scholar
  3. Collins SJ (1987) The HL-60 promyelocytic leukemia cell line; proliferation, differentiation, and cellular oncogene expression. Blood 70: 1233–1244PubMedGoogle Scholar
  4. Evans J, Mire-Sluis A, Hoffbrand V, Wickremasinghe G (1990) Binding of G-CSF, GM-CSF, tumor necrosis factor-α, and γ-interferon to cell surface receptors on human myeloid leukemia cells triggers rapid tyrosine and serine phosphorylation of a 75-kD protein. Blood 75: 88–95PubMedGoogle Scholar
  5. Frank DA and Sartorelli AC (1988) Alterations in tyrosine phosphorylation during the granulocytic maturation of HL-60 leukemia cells. Cancer Res 48: 52–58PubMedGoogle Scholar
  6. Gee CE, Griffin J, Sastre L, Miller LJ, Springer TA, Piwnica-Worms H, Roberts TM (1986) Differentiation of myeloid cells is accompanied by increased levels of pp60c-src protein and kinase activity. Proc Natl Acad Sci USA 83: 5131–5135PubMedCrossRefGoogle Scholar
  7. Heffetz D, Bushkin I, Dror R, Zick Y (1990) The insulinomimetic H2O2 and vanadate stimulate protein tyrosine phosphorylation in intact cells. J Biol Chem 265: 2896–2902PubMedGoogle Scholar
  8. Kraft AS, Berkcw RL (1987) Tyrosine kinase and phosphotyrosine phosphatase activity in human promyelocytic leukemia cells and human polymorphonuclear leukocytes. Blood 70: 356–362PubMedGoogle Scholar
  9. Mangelsdorf DJ, Koeffler HP, Donaldson CA, Pike SW, Haussler MR (1984) 1:25-Dihydroxy vitamin Dg-induced differentiation in human promyelocytic leukemia cell line (HL-60): receptor-mediated maturation to macrophage-like cell. J Cell Biol 98: 391–398Google Scholar
  10. Sariban E, Mitchell T, Kufe D. (1985) Expression of the c-fms proto-oncogene during human monocytic differentiation. Nature 316: 64–66PubMedCrossRefGoogle Scholar
  11. Yu G, Glazer RI (1987) Purification and characterization of p93fes and P60src-related tyrosine protein kinase activities in differentiated HL-60 leukemia cells. J Biol Chem 252: 17543–17548Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • Ilana Bushkin
    • 1
  • Jesse Roth
    • 2
  • Daphna Heffetz
    • 1
  • Yehiel Zick
    • 1
  1. 1.Department of Chemical ImmunologyThe Weizmann Institute of ScienceRehovotIsrael
  2. 2.The Diabetes BranchNIDDK, National Institutes of HealthBethesdaUSA

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