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An Integrated System to Remotely Trigger Intracellular Signal Transduction by Upconversion Nanoparticle-mediated Kinase Photoactivation
Published on: August 30, 2017
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
Summary
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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