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Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1

M Yan1, T Dai, J C Deak

  • 1Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.

Nature
|December 22, 1994
PubMed

Insights

MEK kinase-1 (MEKK) activates stress-activated protein kinases (SAPKs), also known as Jun amino-terminal kinase, not MAPK. MEKK phosphorylates SEK1, which then activates SAPK, revealing a new signaling cascade.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Signal transduction

Background:

  • Mitogen-activated protein kinase (MAPK) signaling is crucial for cellular processes.
  • Raf and MEK kinase-1 (MEKK) are known activators of the MAPK pathway.
  • MEKK was identified by homology to yeast mating pathway kinases.

Purpose of the Study:

  • To investigate the signaling pathway activated by MEKK in NIH3T3 cells.
  • To determine if MEKK activates MAPK or other related kinases.
  • To elucidate the mechanism by which MEKK exerts its cellular effects.

Main Methods:

  • Generation of NIH3T3 cell sublines with inducible MEKK expression.
  • Analysis of kinase activation (MAPK, SAPK/JNK) upon MEKK induction.
  • Investigation of MEKK's role in phosphorylating downstream signaling components like SEK1.

Main Results:

  • Induction of MEKK in NIH3T3 cells did not activate MAPK.
  • MEKK induction led to the activation of stress-activated protein kinases (SAPKs), identified as Jun amino-terminal kinase.
  • MEKK was shown to phosphorylate SEK1, an activator of SAPK, establishing a novel signaling cascade.

Conclusions:

  • MEKK represents an alternative pathway to MAPK activation, specifically targeting the SAPK/JNK cascade.
  • MEKK regulates a distinct signaling pathway involving SEK1 and SAPK.
  • This finding expands our understanding of cellular stress responses and kinase signaling networks.

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