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      Necdin controls EGFR signaling linked to astrocyte differentiation in primary cortical progenitor cells.

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          Abstract

          Cellular signaling mediated by the EGF receptor (EGFR) plays a key role in controlling proliferation and differentiation of cortical progenitor cells (CPCs). However, regulatory mechanisms of EGFR signaling in CPCs remain largely unknown. Here we demonstrate that necdin, a MAGE (melanoma antigen) family protein, interacts with EGFR in primary CPCs and represses its downstream signaling linked to astrocyte differentiation. EGFR was autophosphorylated and interacted with necdin in EGF-stimulated CPCs. Necdin bound to autophosphorylated EGFR via its tyrosine kinase domain. EGF-induced phosphorylation of ERK was enhanced in necdin-null CPCs, where the interaction between EGFR and the adaptor protein Grb2 was strengthened, suggesting that endogenous necdin suppresses the EGFR/ERK signaling pathway in CPCs. In necdin-null CPCs, astrocyte differentiation induced by the gliogenic cytokine cardiotrophin-1 was significantly accelerated in the presence of EGF, and inhibition of EGFR/ERK signaling abolished the acceleration. Furthermore, necdin strongly suppressed astrocyte differentiation induced by overexpression of EGFR or its ligand binding-defective mutant equivalent to a glioblastoma-associated EGFR variant. These results suggest that necdin acts as an intrinsic suppressor of the EGFR/ERK signaling pathway in EGF-responsive CPCs to restrain astroglial development in a cell-autonomous manner.

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          Author and article information

          Journal
          Cell. Signal.
          Cellular signalling
          1873-3913
          0898-6568
          Feb 2016
          : 28
          : 2
          Affiliations
          [1 ] Laboratory of Regulation of Neuronal Development, Institute for Protein Research, Osaka University, Osaka, Japan.
          [2 ] Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Osaka, Japan.
          [3 ] Laboratory of Regulation of Neuronal Development, Institute for Protein Research, Osaka University, Osaka, Japan. Electronic address: yoshikaw@protein.osaka-u.ac.jp.
          Article
          S0898-6568(15)30006-1
          10.1016/j.cellsig.2015.11.016
          26655377
          8810e5ac-c478-4e30-b133-b9eeb021c4be
          Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
          History

          EGFR,ERK,Gliogenesis,MAGE family,Necdin
          EGFR, ERK, Gliogenesis, MAGE family, Necdin

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