Protein kinase D mediates a stress-induced NF-κB activation and survival pathway

Peter Storz, Alex Toker

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

The activation of the transcription factor NF-κB is critical for a number of physiological responses. Here, we provide evidence for a signaling pathway that mediates NF-κB activation in response to oxidative stress. We show that tyrosine phosphorylation of protein kinase D (PKD) at Y463 in the Pleckstrin Homology (PH) domain is mediated by the Src and Abl tyrosine kinase signaling pathway, and that this is both necessary and sufficient to activate NF-κB in response to oxidative stress. PKD activates NF-κB through the IKK complex and more specifically, IKKβ, leading to IκBα degradation. We also present evidence that this pathway is required for increased cellular survival in response to oxidative stress. We propose a model in which protection from oxidative stress-induced cell death requires the tyrosine phosphorylation of PKD leading to the activation of the transcription factor NF-κB.

Original languageEnglish (US)
Pages (from-to)109-120
Number of pages12
JournalEMBO Journal
Volume22
Issue number1
DOIs
StatePublished - Jan 2 2003
Externally publishedYes

Fingerprint

Oxidative stress
Oxidative Stress
Chemical activation
Phosphorylation
Protein-Tyrosine Kinases
Tyrosine
Transcription Factors
src-Family Kinases
Cell death
Cell Death
Degradation
protein kinase D

Keywords

  • Abl
  • IKK
  • NF-κB
  • PKD
  • Src

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Protein kinase D mediates a stress-induced NF-κB activation and survival pathway. / Storz, Peter; Toker, Alex.

In: EMBO Journal, Vol. 22, No. 1, 02.01.2003, p. 109-120.

Research output: Contribution to journalArticle

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