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The neuronal adaptor protein Fe65 is phosphorylated by mitogen-activated protein kinase (ERK1/2)

Claire L Standen1, Michael S Perkinton, Helen L Byers

  • 1Department of Neuroscience, The Institute of Psychiatry, Kings College, London, UK.

Molecular and Cellular Neurosciences
|December 31, 2003
PubMed

Insights

Fe65, a neuronal adaptor protein, is phosphorylated by ERK1/2 kinases. This phosphorylation at specific in vivo sites provides a mechanism for regulating Fe65

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Fe65 is a neuronal adaptor protein involved in nuclear signaling and cell motility.
  • Its diverse functions are mediated by interactions with various binding partners, forming complexes like Fe65/APP/TIP60 and Fe65/APP/Mena.
  • The regulatory mechanisms governing Fe65's distinct roles remain largely unknown.

Purpose of the Study:

  • To investigate the post-translational modifications of Fe65.
  • To identify specific in vivo phosphorylation sites on Fe65.
  • To determine if Fe65 is a substrate for mitogen-activated protein kinases (MAPKs).

Main Methods:

  • Phosphoproteomic analysis using mass spectrometry sequencing.
  • In vitro kinase assays to test Fe65 phosphorylation by ERK1/2.

Main Results:

  • Fe65 was identified as a phosphoprotein.
  • Novel in vivo phosphorylation sites within Fe65 were mapped using mass spectrometry.
  • Fe65 was confirmed as a direct substrate for phosphorylation by ERK1/2.

Conclusions:

  • Phosphorylation by ERK1/2 represents a key regulatory mechanism for Fe65 function.
  • This finding elucidates how Fe65's roles in transcription and cell migration may be modulated.
  • The study provides a molecular basis for understanding Fe65's involvement in neuronal processes.

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