TY - JOUR
T1 - SOCS3 negatively regulates LIF signaling in neural precursor cells
AU - Emery, B.
AU - Merson, T. D.
AU - Snell, C.
AU - Young, K. M.
AU - Ernst, M.
AU - Kilpatrick, T. J.
N1 - Funding Information:
This work was supported by the National Health and Medical Research Council of Australia and the National Multiple Sclerosis Society of the USA. We thank Dr. Warren Alexander, The Walter and Eliza Hall Institute, for providing the SOCS3 knockout mice.
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.mcn.2006.01.005
DO - 10.1016/j.mcn.2006.01.005
M3 - Article
C2 - 16497512
AN - SCOPUS:33645352788
SN - 1044-7431
VL - 31
SP - 739
EP - 747
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 4
ER -