title: Imipramine administration induces changes in the phosphorylation of FAK and PYK2 and modulates signaling pathways related to their activity.
abstract: BACKGROUND
  Antidepressants can modify neuronal functioning by affecting many levels of signal transduction pathways that are involved in neuroplasticity. We investigated whether the phosphorylation status of focal adhesion kinase (FAK/PTK2) and its homolog, PYK2/PTK2B, and their complex with the downstream effectors (Src kinase, p130Cas, and paxillin) are affected by administration of the antidepressant drug, imipramine. The treatment influence on the levels of ERK1/2 kinases and their phosphorylated forms (pERK1/2) or the Gαq, Gα11 and Gα12 proteins were also assessed.
  
  
  METHODS
  Rats were injected with imipramine (10 mg/kg, twice daily) for 21 days. The levels of proteins investigated in their prefrontal cortices were measured by Western blotting.
  
  
  RESULTS
  Imipramine induced contrasting changes in the phosphorylation of FAK and PYK2 at Tyr397 and Tyr402, respectively. The decreased FAK phosphorylation and increased PYK2 phosphorylation were reflected by changes in the levels of their complex with Src and p130Cas, which was observed predominantly after chronic imipramine treatment. Similarly only chronic imipramine decreased the Gαq expression while Gα11 and Gα12 proteins were untouched. Acute and chronic treatment with imipramine elevated ERK1 and ERK2 total protein levels, whereas only the pERK1 was significantly affected by the drug.
  
  
  CONCLUSIONS
  The enhanced activation of PYK2 observed here could function as compensation for FAK inhibition.
  
  
  CONCLUSIONS
  These data demonstrate that treatment with imipramine, which is a routine in counteracting depressive disorders, enhances the phosphorylation of PYK2, a non-receptor kinase instrumental in promoting synaptic plasticity. This effect documents as yet not considered target in the mechanism of imipramine action.
authors.affiliation: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Zalewska
authors.affiliation: Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Bielawski
authors.affiliation: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Luiza
authors.initials: L
authors.lastname: Stanaszek
authors.affiliation: Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wieczerzak
authors.affiliation: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Ziemka-Nałęcz
authors.affiliation: Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. Electronic address: nfnalepa@cyf-kr.edu.pl.
authors.forename: Irena
authors.initials: I
authors.lastname: Nalepa
mesh_terms: D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000032:analysis; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051419:Paxillin; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D007099:Imipramine
keywords: Antidepressant drug; ERK1/2; Focal adhesion kinases; G proteins; Rat prefrontal cortex