Abstract
In Jurkat T lymphocytes, hydrogen peroxide (H(2)O(2)) potentiates the phosphorylation level of extracellular signal-regulated kinase 1 and 2 (ERK1/2) caused by T cell receptor (TCR) stimulation with anti-CD3 and anti-CD28 or anti-CD3 alone. Submillimolar concentrations of H(2)O(2)-induced phosphorylation of ERK1/2 and MAP/ERK kinase 1 and 2 (MEK1/2) without antigenic stimulation. H(2)O(2) also induced the electrophoretic mobility shift of Lck from 56 to 60 kDa. The MEK inhibitor, PD98059 attenuated ERK1/2 and MEK1/2 phosphorylation, as well as the migration shift of Lck induced by H(2)O(2). The phospholipase C (PLC) inhibitor, U73122, and EGTA reduced the phosphorylation of both ERK1/2 and MEK1/2 induced by H(2)O(2). Interestingly, an increase of intracellular cAMP level with forskolin or 8-(4-chlorophenylthio)-cAMP augmented ERK1/2 phosphorylation by H(2)O(2), while inhibiting MEK1/2 phosphorylation by H(2)O(2). These results demonstrate an alternative pathway that results in augmentation of ERK1/2 phosphorylation without concomitant MEK1/2 phosphorylation in T cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Colforsin / pharmacology
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Cyclic AMP / physiology*
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Drug Synergism
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Enzyme Inhibitors / pharmacology
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Estrenes / pharmacology
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Flavonoids / pharmacology
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Humans
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Hydrogen Peroxide / pharmacology*
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Jurkat Cells
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
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MAP Kinase Kinase 1
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MAP Kinase Kinase 2
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MAP Kinase Signaling System / drug effects
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinase Kinases / metabolism*
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Pyrrolidinones / pharmacology
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Receptors, Antigen, T-Cell / physiology
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T-Lymphocytes / immunology*
Substances
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Enzyme Inhibitors
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Estrenes
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Flavonoids
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Pyrrolidinones
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Receptors, Antigen, T-Cell
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Colforsin
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Hydrogen Peroxide
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Cyclic AMP
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MAP2K2 protein, human
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Protein-Tyrosine Kinases
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Protein Serine-Threonine Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 1
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MAP Kinase Kinase 2
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MAP2K1 protein, human
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Mitogen-Activated Protein Kinase Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one