Activation of the SAPK Pathway by the Human STE20 Homologue Germinal Centre Kinase

Nature. 1995 Oct 26;377(6551):750-4. doi: 10.1038/377750a0.

Abstract

Eukaryotic cells respond to different extracellular stimuli by recruiting homologous signalling pathways that use members of the MEKK, MEK and ERK families of protein kinases. The MEKK-->MEK-->ERK core pathways of Saccharomyces cerevisiae may themselves be regulated by members of the STE20 family of protein kinases. Here we report specific activation of the mammalian stress-activated protein kinase (SAPK) pathway by germinal centre kinase (GCK), a human STE20 homologue. SAPKs, members of the ERK family, are activated in situ by inflammatory stimuli, including tumour-necrosis factor (TNF) and interleukin-1, and phosphorylate and probably stimulate the transactivation function of c-Jun. Although GCK is found in many tissues, its expression in lymphoid follicles is restricted to the cells of the germinal centre, where it may participate in B-cell differentiation. Activation of the SAPK pathway by GCK illustrates further the striking conservation of eukaryotic signalling mechanisms and defines the first physiological function of a mammalian Ste20.

Publication types

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

MeSH terms

  • Anisomycin / pharmacology
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Enzyme Activation
  • Germinal Center Kinases
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • MAP Kinase Kinase 4*
  • MAP Kinase Kinase Kinases
  • Mitogen-Activated Protein Kinase Kinases*
  • Molecular Sequence Data
  • Protein Kinases / agonists
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • DNA Primers
  • Germinal Center Kinases
  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • Anisomycin
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases
  • STE20 protein, S cerevisiae
  • MAP Kinase Kinase 4
  • MAP2K4 protein, human
  • Mitogen-Activated Protein Kinase Kinases