A protein kinase involved in the regulation of inflammatory cytokine biosynthesis

Nature. 1994 Dec 22-29;372(6508):739-46. doi: 10.1038/372739a0.

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.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Chromosomes, Human, Pair 6
  • Cloning, Molecular
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis*
  • DNA, Complementary
  • Humans
  • Imidazoles / pharmacology
  • Inflammation Mediators*
  • Interleukin-1 / biosynthesis
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Peptide Fragments
  • Pyridines / pharmacology
  • Radioligand Assay
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Cytokines
  • DNA, Complementary
  • Imidazoles
  • Inflammation Mediators
  • Interleukin-1
  • Peptide Fragments
  • Pyridines
  • Recombinant Proteins
  • SB 206718
  • Tumor Necrosis Factor-alpha
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole

Associated data

  • GENBANK/L35263
  • GENBANK/L35264