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Imipramine administration induces changes in the phosphorylation of FAK and PYK2 and modulates signaling pathways

Teresa Zalewska1, Adam Bielawski2, Luiza Stanaszek1

  • 1NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

Biochimica Et Biophysica Acta
|December 2, 2015
PubMed
Abstract

Insights

Imipramine treatment alters focal adhesion kinase (FAK) and PYK2 phosphorylation, enhancing PYK2 activation. This suggests a novel mechanism for imipramine

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Antidepressants modulate neuronal signaling pathways crucial for neuroplasticity.
  • Focal adhesion kinase (FAK/PTK2) and its homolog PYK2/PTK2B are key regulators of neuronal function.
  • Investigating imipramine's effects on FAK, PYK2, and associated signaling proteins is essential for understanding its mechanism of action.

Purpose of the Study:

  • To determine how imipramine affects the phosphorylation status of FAK and PYK2.
  • To analyze the impact of imipramine on the complex formation of FAK/PYK2 with downstream effectors like Src kinase, p130Cas, and paxillin.
  • To assess imipramine's influence on ERK1/2 kinases and G-protein subunits (Gαq, Gα11, Gα12).

Main Methods:

  • Rats received imipramine (10 mg/kg, twice daily) for 21 days.
  • Protein levels in prefrontal cortices were quantified using Western blotting.

Main Results:

  • Imipramine induced differential phosphorylation of FAK (decreased at Tyr397) and PYK2 (increased at Tyr402).
  • Chronic imipramine treatment altered the complex formation of FAK/PYK2 with Src and p130Cas.
  • Imipramine increased total ERK1/2 levels and specifically phosphorylated ERK1, while decreasing Gαq expression.

Conclusions:

  • Enhanced PYK2 activation may compensate for imipramine-induced FAK inhibition.
  • Imipramine promotes PYK2 phosphorylation, a critical kinase for synaptic plasticity.
  • This study identifies a previously unrecognized target of imipramine's action in treating depressive disorders.
Keywords:
Antidepressant drugERK1/2Focal adhesion kinasesG proteinsRat prefrontal cortex

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