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The roles of protein phosphorylation/dephosphorylation in tumor necrosis factor antitumor effects

X Y Wang1, M Kafka, A Dvilansky

  • 1Department of Hematology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
|December 1, 1996
PubMed

Insights

Tumor necrosis factor (TNF) affects cell growth and death. Inhibiting tyrosine phosphorylation enhances TNF's effects, revealing specific protein targets involved in TNF signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein phosphorylation and dephosphorylation are critical regulatory mechanisms in cellular signaling.
  • Tumor necrosis factor-alpha (TNF-alpha) plays a significant role in inflammation, immunity, and cell death.
  • Understanding the molecular mechanisms of TNF-alpha action is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the roles of protein phosphorylation and dephosphorylation in TNF-alpha's cytotoxic and antiproliferative effects.
  • To identify specific proteins involved in TNF-alpha signaling pathways.
  • To explore the potential of tyrosine kinase inhibitors in modulating TNF-alpha activity.

Main Methods:

  • Utilized L-929-transformed fibroblasts as a cellular model.
  • Employed genistein and erbstatin as specific tyrosine kinase inhibitors.
  • Performed immunoblot analysis with antiphosphotyrosine antibodies to detect protein phosphorylation changes.

Main Results:

  • TNF-alpha induced tyrosine dephosphorylation of 34-36 kDa and 50-52 kDa membranal proteins.
  • TNF-alpha potentiated tyrosine phosphorylation of a 115-kDa protein in cytosolic and membranal fractions.
  • Genistein synergistically enhanced both cytotoxic and antiproliferative effects of TNF-alpha.

Conclusions:

  • Inhibition of tyrosine phosphorylation can potentiate TNF-alpha activity.
  • Specific protein dephosphorylation events are associated with TNF-alpha signaling.
  • Targeting tyrosine kinases may offer a strategy to modulate TNF-alpha-mediated cellular responses.

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