Reactive oxygen species mediate phorbol ester-regulated tyrosine phosphorylation and phospholipase A2 activation

Potentiation by vanadate

U. Zor, E. Ferber, P. Gergely, K. Szucs, V. Dombrádi, R. Goldman

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

We have previously shown that vanadate potentiates the activating effect of phorbol ester (TPA) on cellular phospholipase A2 (PLA2) in a pathway dependent on the formation of reactive oxygen species (ROS). Here we evaluate the chain of enzymes (protein kinases and phosphatases) that participate in this process. Treatment of macrophages with vanadate plus TPA led to activation of protein kinase C (PKC) and NADPH oxidase (O2- generation in intact cells), massive cellular protein tyrosine phosphorylation, suppression of protein tyrosine phosphatase (PTP) activity and a sustained activation of protein tyrosine kinase (PTK) and myelin basic protein kinase activity (the latter three enzyme activities were assessed in cell lysates). Inhibition of ROS formation by diphenyleneiodonium (DPI) prevented PTP inhibition, PTK activation and protein tyrosine phosphorylation by vanadate plus TPA. Vanadate plus H2O2 mimicked the effect of vanadate plus TPA on PKC activation, cellular protein tyrosine phosphorylation, PTP and PTK, but their effects were resistant to DPI. Suppression of PKC activity (down-regulation; selective inhibitors) prevented the above-mentioned effects of vanadate plus TPA, but not of vanadate plus H2O2. Collectively, the results show that ROS formation induced by TPA in association with vanadate is essential in the modulation of protein tyrosine phosphorylation and PLA2 activity.

Original languageEnglish
Pages (from-to)879-888
Number of pages10
JournalBiochemical Journal
Volume295
Issue number3
Publication statusPublished - 1993

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Phosphorylation
Vanadates
Phospholipases A2
Phorbol Esters
Tyrosine
Reactive Oxygen Species
Chemical activation
Protein Tyrosine Phosphatases
Protein-Tyrosine Kinases
Protein Kinase C
Protein Kinases
Proteins
Enzyme inhibition
Myelin Basic Protein
Macrophages
NADPH Oxidase
Phosphoprotein Phosphatases
Enzyme activity
Enzymes
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Reactive oxygen species mediate phorbol ester-regulated tyrosine phosphorylation and phospholipase A2 activation : Potentiation by vanadate. / Zor, U.; Ferber, E.; Gergely, P.; Szucs, K.; Dombrádi, V.; Goldman, R.

In: Biochemical Journal, Vol. 295, No. 3, 1993, p. 879-888.

Research output: Contribution to journalArticle

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