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NAK is an IkappaB kinase-activating kinase

Y Tojima1, A Fujimoto, M Delhase

  • 1Department of Geriatric Research, National Institute for Longevity Sciences, Obu, Aichi, Japan.

Nature
|April 28, 2000
PubMed

Insights

Researchers discovered a new kinase, NF-kappaB-activating kinase (NAK), that activates the IkappaB kinase (IKK) complex. This finding sheds light on how extracellular signals activate the NF-kappaB pathway.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Immunology

Background:

  • The IkappaB kinase (IKK) complex regulates the transcription factor NF-kappaB, crucial in inflammatory responses.
  • IKK activation involves phosphorylation of IKKbeta, but the upstream kinases remain largely unknown.
  • NF-kappaB activation is critical for immune responses and cellular processes.

Purpose of the Study:

  • To identify and characterize novel kinases that activate the IKK complex.
  • To elucidate the upstream signaling mechanisms controlling IKK and NF-kappaB activation by extracellular stimuli.

Main Methods:

  • Biochemical assays to identify kinase activity.
  • In vitro phosphorylation studies using recombinant proteins.
  • Cell-based assays to assess NF-kappaB activation and IkappaB degradation.

Main Results:

  • A novel IKK-related kinase, named NAK (NF-kappaB-activating kinase), was identified.
  • NAK directly phosphorylates and activates the IKK complex, leading to IkappaB degradation and NF-kappaB activation.
  • Endogenous NAK is activated by phorbol esters and growth factors, and its activity is linked to protein kinase C-epsilon (PKCepsilon).

Conclusions:

  • NAK is a key upstream kinase that mediates IKK and NF-kappaB activation.
  • NAK represents a potential therapeutic target for modulating inflammatory and cellular responses.
  • This study reveals a novel signaling axis involving NAK, IKK, and NF-kappaB.

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