Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine
Graduate School of Biomedical Sciences; Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Biology; Program in Molecular Medicine
Medical Subject Headings
Animals; Calcium-Calmodulin-Dependent Protein Kinases; purification; Cell Line; Cercopithecus aethiops; Enzyme Activation; Hela Cells; Humans; Inflammation; Interleukin-1; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Mitogen-Activated Protein Kinase 3; *Mitogen-Activated Protein Kinases; Molecular Weight; Osmolar Concentration; Phosphorylation; Phosphothreonine; Phosphotyrosine; Recombinant Proteins; Sequence Deletion; Stress; Subcellular Fractions; Substrate Specificity; *Threonine; Transfection; Tumor Necrosis Factor-alpha; *Tyrosine
Life Sciences | Medicine and Health Sciences
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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Citation: J Biol Chem. 1995 Mar 31;270(13):7420-6.
The Journal of biological chemistry
Raingeaud, Joel; Gupta, Shashi; Rogers, Jeffrey Scott; Dickens, Martin; Han, Jiahuai; Ulevitch, Richard J.; and Davis, Roger J., "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine" (1995). GSBS Student Publications. 1009.