Involvement of non-receptor protein kinases in the mechanism of imipramine action

• Autorzy: Zalewska T. , Zajac H. , Bielawski A. , Nalepa I.
• Języki publikacji: EN

Abstrakty

EN

Chronic treatment with antidepressant imipramine increases synaptic plasticity and connectivity in the rat brain. Signals that orchestrate changes associated with neuronal plasticity derive in part from extracellular matrix (ECM). Two homologous tyrosine kinases ñ FAK and PYK2 are thought to play a major role in transducing signals from extracellular matrix to the cell interior. This prompted us to examine the effect of acute and chronic imipramine treatment on the activity of FAK and PYK2-dependent signaling pathway in the rat brain cortex. To approach this problem we aimed to quantify the level of FAK and PYK2 phosphorylation of their tyrosine residues as well as interaction of these kinases with downstream signaling substrates such as the Src kinase, adaptor protein p130Cas, and cytoskeletal protein-paxilin. Our results demonstrate different responses of the two kinases to the imipramine administration. Imipramine leads to the suppression of FAK-dependent pathway with simultaneous stimulation of the pathway coupled with PYK2 kinase. The reduction in FAK Tyr 397 phosphorylation, in particular after chronic administration of the drug, was translated into a decreased association of FAK with downstream molecular partners, Src kinase and p130Cas. In contrast, the acute and chronic treatment with imipramine leads to activation of 402 tyrosine phosphorylation of PYK2 kinase and in consequence increased interaction with kinase Src and adaptor protein p130Cas. Because both kinases appear to be well suited to play a role in synaptic plasticity, it seems probably that PYK2 may function in a compensatory manner for the FAK inhibition and may be responsible for neuronal plasticity-connected events after imipramine treatment. Supported by Polish MNSW Scientifi c Network Fund

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.86

Twórcy

autor

Zalewska T.

• NeroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Zajac H.

• NeroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Bielawski A.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Nalepa I.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland