title: Glucocorticoid suppresses BDNF-stimulated MAPK/ERK pathway via inhibiting interaction of Shp2 with TrkB.
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.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Kumamaru
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Adachi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009474:Neurons / Q000201:enzymology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D003907:Dexamethasone; D020813:Receptor, trkB; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11