A protein kinase involved in the regulation of inflammatory cytokine biosynthesis

Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitoge...

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Bibliographic Details
Published in:	Nature (London) Vol. 372; no. 6508; pp. 739 - 746
Main Authors:	Lee, John C, Laydon, Jeffrey T, McDonnell, Peter C, Gallagher, Timothy F, Kumar, Sanjay, Green, David, McNulty, Dean, Blumenthal, Mary Jane, Keys, J. Richard, Land vatter, Scott W, Strickler, James E, McLaughlin, Megan M, Siemens, Ivo R, Fisher, Seth M, Livi, George P, White, John R, Adams, Jerry L, Young, Peter R
Format:	Journal Article
Language:	English
Published:	London Nature Publishing 22-12-1994 Nature Publishing Group
Subjects:	Amino Acid Sequence Analysis of the immune response. Humoral and cellular immunity Base Sequence Biochemistry Biological and medical sciences Biosynthesis Calcium-Calmodulin-Dependent Protein Kinases - genetics Calcium-Calmodulin-Dependent Protein Kinases - metabolism cDNA Cell Line Cellular biology Chromosomes, Human, Pair 6 cloning Cloning, Molecular CSBP protein Cytokines - antagonists & inhibitors Cytokines - biosynthesis Deoxyribonucleic acid DNA DNA, Complementary Fundamental and applied biological sciences. Psychology Fundamental immunology genes Humans Imidazoles - pharmacology Immunobiology inflammation Inflammation Mediators Interleukin-1 - biosynthesis Lymphokines, interleukins ( function, expression) man Mitogen-Activated Protein Kinases Molecular Sequence Data monocytes Monocytes - drug effects Monocytes - metabolism nucleotide sequence p38 Mitogen-Activated Protein Kinases Peptide Fragments prediction Probes protein kinase Proteins Pyridines - pharmacology Radioligand Assay Recombinant Proteins - genetics Recombinant Proteins - metabolism Regulatory factors and their cellular receptors Tumor Necrosis Factor-alpha - biosynthesis Human Imidazole derivatives Monocyte Ligand Cytokine Antiinflammatory agent Biosynthesis In vitro Characterization Regulation(control) Pyridine Tumor necrosis factor Interleukin 1 Inhibition Molecular cloning Mechanism of action
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Summary:	Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0028-0836 1476-4687
DOI:	10.1038/372739a0