细胞因子信号转导抑制因子3（SOCS3）对神经前体细胞中的白血病抑制因子（LIF）信号传导起负向调节作用。
SOCS3 negatively regulates LIF signaling in neural precursor cells.
作者信息
Emery B, Merson T D, Snell C, Young K M, Ernst M, Kilpatrick T J
机构信息
Multiple Sclerosis Group, The Howard Florey Institute, University of Melbourne, Melbourne, Victoria 3010, Australia.
出版信息
Mol Cell Neurosci. 2006 Apr;31(4):739-47. doi: 10.1016/j.mcn.2006.01.005. Epub 2006 Feb 23.
Cytokines that signal through the LIFRbeta/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 SOCS3WT/WT but not SOCS3KO/KO NPCs is enhanced by exogenous LIF. Thus, SOCS3 acts as a negative regulator of LIF signaling in NPCs.
通过白血病抑制因子受体β/糖蛋白130（LIFRβ/gp130）受体复合物发出信号的细胞因子，包括白血病抑制因子（LIF）和睫状神经营养因子（CNTF），可促进胚胎和成体神经前体细胞（NPC）的自我更新。在非中枢神经系统组织中，细胞因子信号传导抑制蛋白3（SOCS3）对通过gp130的信号传导起负调节作用。在此，我们分析了SOCS3在体外抑制NPC中LIF信号传导的作用。NPC对LIF刺激反应迅速表达SOCS3，这种表达很大程度上依赖于信号转导和转录激活因子（STAT）蛋白募集到活化的gp130受体。可从SOCS3基因敲除（SOCS3KO/KO）胚胎中生成增殖性NPC培养物，其对LIF反应显示出延长的STAT3磷酸化和胶质纤维酸性蛋白（GFAP）基因的诱导。与SOCS3野生型（SOCS3WT/WT）NPC相比，SOCS3KO/KO培养物显示出增强的自我更新能力。然而，外源性LIF增强了SOCS3WT/WT而非SOCS3KO/KO NPC的克隆潜力。因此，SOCS3在NPC中作为LIF信号传导的负调节因子发挥作用。
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