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[摘要]：Increased glucocorticoids (GCs) have been implicated in the pathophysiology of depressive disorder. We previously found that dexamethasone (DEX, a synthetic GC) repressed brain-derived neurotrophic factor (BDNF)-induced synaptic proteins via suppressing extracellular signal-regulated protein kinase (ERK) signaling. Here, we investigated the possible involvement of Src homology-2 domain-containing phosphatase2 (Shp2), an ERK signaling mediator. We found that DEX suppressed Shp2 interaction with TrkB, a receptor for BDNF, in cultured cortical neurons. NSC87877, a Shp2 inhibitor, mimicked DEX, and Shp2 overexpression reversed the effect of DEX, suggesting that GCs suppress ERK signaling through inhibiting the interaction of Shp2 with TrkB. Structured summary of protein interactions: TrkB physically interacts with Shp2 by anti bait coimmunoprecipitation (View interaction) FRS2 physically interacts with Shp2 by anti bait coimmunoprecipitation (View interaction) Grb2 physically interacts with Shp2 by anti bait coimmunoprecipitation (View interaction) (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. |
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