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A protein kinase involved in the regulation of inflammatory cytokine biosynthesis

Nature volume 372, pages 739–746 (1994)Cite this article

Abstract

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.

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Author information

Author notes

  1. David Green

    Present address: Bristol-Myers-Squibb Pharmaceutical Research Institute, Princeton, New Jersey, 08543, USA

  2. James E. Strickler

    Present address: Ares Advanced Technology, Randolph, Massachusetts, 02368, USA

Affiliations

  1. Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, 19406, USA

    John C. Lee, Jeffrey T. Laydon & Mary Jane Blumenthal

  2. Department of Molecular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, 19406, USA

    Peter C. McDonnell, Sanjay Kumar, John R. White & Peter R. Young

  3. Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, 19406, USA

    Timothy F. Gallagher & Jerry L. Adams

  4. Department of Radiochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, 19406, USA

    J. Richard Keys & Scott W. Land vatter

  5. Department of Protein Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, 19406, USA

    David Green, Dean McNulty, James E. Strickler, Ivo R. Siemens & Seth M. Fisher

  6. Department of Gene Expression Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, 19406, USA

    Megan M. McLaughlin & George P. Livi

Authors
  1. John C. Lee
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  2. Jeffrey T. Laydon
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  6. David Green
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  7. Dean McNulty
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  8. Mary Jane Blumenthal
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  9. J. Richard Keys
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  11. James E. Strickler
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  12. Megan M. McLaughlin
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  14. Seth M. Fisher
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  15. George P. Livi
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  18. Peter R. Young
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Cite this article

Lee, J., Laydon, J., McDonnell, P. et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372, 739–746 (1994). https://doi.org/10.1038/372739a0

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