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  • Title: Glucocorticoid suppresses BDNF-stimulated MAPK/ERK pathway via inhibiting interaction of Shp2 with TrkB.
    Author: Kumamaru E, Numakawa T, Adachi N, Kunugi H.
    Journal: FEBS Lett; 2011 Oct 20; 585(20):3224-8. PubMed ID: 21946312.
    Abstract:
    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.
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