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The activation loop phosphorylation of protein kinase D is an early marker of neuronal DNA damage

Cagri G Besirli1, Eugene M Johnson

  • 1Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.

Journal of Neurochemistry
|August 17, 2006
PubMed

Insights

Protein kinase D (PKD) is an early indicator of neuronal DNA damage, activating rapidly after genotoxic stress. Its downstream signaling may be crucial for neuron survival following DNA damage.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • DNA damage in neurons triggers apoptosis via the mitochondrial pathway.
  • Signaling pathways activated by genotoxic stress upstream of mitochondria are not well understood.

Purpose of the Study:

  • To identify early molecular markers of neuronal DNA damage.
  • To investigate the role of protein kinase D (PKD) in the response to genotoxic stress in neurons.

Main Methods:

  • Assessed protein kinase D (PKD) phosphorylation as a marker of DNA damage.
  • Utilized genotoxic stress stimuli and measured PKD activation kinetics.
  • Examined PKD activation in vivo in rat neuronal tissues after etoposide injection.

Main Results:

  • PKD activation, indicated by phosphorylation, was detected within 15 minutes of genotoxic stress, concurrent with ATM activation.
  • PKD stimulation was specific to DNA damage and not observed with other stress types.
  • In vivo studies confirmed increased phosphorylated PKD levels in rat neuronal tissues post-etoposide treatment.

Conclusions:

  • Protein kinase D (PKD) is an early responder to neuronal DNA damage.
  • PKD activation is a selective marker for genotoxic stress in neurons.
  • Signaling pathways downstream of PKD are potentially critical for neuronal survival after DNA damage.

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