Phosphoproteomic analysis of neurotrophin receptor TrkB signaling pathways in mouse brain.

Cellular and Molecular Neurobiology
Artour SemenovE Castrén

Abstract

1. The signaling pathways activated by trkB neurotrophin receptor have been studied in detail in cultured neurons, but little is known about the pathways activated by trkB in intact brain. TrkB is a tyrosine kinase and protein phosphorylation is a key regulatory process in the neuronal signal transduction pathways. 2. We have investigated trkB signaling in the transgenic mice overexpressing trkB in postnatal neurons (trkB.TK) using phosphoproteomics. 3. We found that several proteins are overphosphorylated on tyrosine residues in the brain of trkB.TK mice and identified some of these proteins. 4. We demonstrate that the well characterized signaling molecules mitogen-activated protein kinase (MAPK) and cyclic AMP responsive element binding protein (CREB) were phosphorylated at a higher level in the brain of trkB.TK mice when compared to the wild type littermates. Furthermore, we found that beta-actin was tyrosine phosphorylated in the brain of the transgenic mice. 5. Our results demonstrate that phosphoproteomics is a sensitive approach to investigate signaling pathways activated in mouse brain.

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Citations

Jan 3, 2012·Neurobiology of Aging·Susanna KemppainenHeikki Tanila
Sep 14, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Nurhan OzluJudith A J Steen
May 28, 2011·Journal of Psychiatric Research·Daniel Martins-de-SouzaSabine Bahn

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