SOCS3 negatively regulates LIF signaling in neural precursor cells

B. Emery, T. D. Merson, C. Snell, K. M. Young, M. Ernst, T. J. Kilpatrick

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Cytokines that signal through the LIFRβ/gp130 receptor complex, including LIF and CNTF, promote the self-renewal of embryonic and adult neural precursor cells (NPCs). In non-CNS tissues, the protein suppressor of cytokine signaling-3 (SOCS3) negatively regulates signaling through gp130. Here, we analyze the role of SOCS3 in inhibiting LIF signaling in NPCs in vitro. SOCS3 is rapidly expressed by NPCs in response to LIF stimulation, with this expression largely dependent on recruitment of STAT proteins to the activated gp130 receptor. Proliferating NPC cultures can be generated from SOCS3 knockout (SOCS3KO/KO) embryos and display prolonged STAT3 phosphorylation and induction of the GFAP gene in response to LIF. In comparison with SOCS3 wild-type (SOCS3WT/WT) NPCs, SOCS3KO/KO cultures display enhanced self-renewal capacity. However, the clonal potential of SOCS3 WT/WT but not SOCS3KO/KO NPCs is enhanced by exogenous LIF. Thus, SOCS3 acts as a negative regulator of LIF signaling in NPCs.

Original languageEnglish (US)
Pages (from-to)739-747
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Emery, B., Merson, T. D., Snell, C., Young, K. M., Ernst, M., & Kilpatrick, T. J. (2006). SOCS3 negatively regulates LIF signaling in neural precursor cells. Molecular and Cellular Neuroscience, 31(4), 739-747. https://doi.org/10.1016/j.mcn.2006.01.005