Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine

J Biol Chem. 1995 Mar 31;270(13):7420-6. doi: 10.1074/jbc.270.13.7420.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / analysis
  • Calcium-Calmodulin-Dependent Protein Kinases / isolation & purification
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Chlorocebus aethiops
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • Inflammation
  • Interleukin-1 / pharmacology*
  • JNK Mitogen-Activated Protein Kinases
  • Lipopolysaccharides / pharmacology*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Molecular Weight
  • Osmolar Concentration
  • Phosphorylation
  • Phosphothreonine / metabolism
  • Phosphotyrosine
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Stress, Physiological
  • Subcellular Fractions / enzymology
  • Substrate Specificity
  • Threonine*
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Tyrosine* / analogs & derivatives
  • Tyrosine* / metabolism

Substances

  • Interleukin-1
  • Lipopolysaccharides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Phosphothreonine
  • Phosphotyrosine
  • Threonine
  • Tyrosine
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases