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Title
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Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine.
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Authors
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J.Raingeaud,
S.Gupta,
J.S.Rogers,
M.Dickens,
J.Han,
R.J.Ulevitch,
R.J.Davis.
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Ref.
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J Biol Chem, 1995,
270,
7420-7426.
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PubMed id
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Abstract
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Protein kinases activated by dual phosphorylation on Tyr and Thr (MAP kinases)
can be grouped into two major classes: ERK and JNK. The ERK group regulates
multiple targets in response to growth factors via a Ras-dependent mechanism. In
contrast, JNK activates the transcription factor c-Jun in response to
pro-inflammatory cytokines and exposure of cells to several forms of
environmental stress. Recently, a novel mammalian protein kinase (p38) that
shares sequence similarity with mitogen-activated protein (MAP) kinases was
identified. Here, we demonstrate that p38, like JNK, is activated by treatment
of cells with pro-inflammatory cytokines and environmental stress. The mechanism
of p38 activation is mediated by dual phosphorylation on Thr-180 and Tyr-182.
Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in
both the nucleus and cytoplasm of activated cells. Together, these data
establish that p38 is a member of the mammalian MAP kinase group.
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