SNT-2与ERK2相互作用，并在表皮生长因子（EGF）刺激下负向调节ERK2信号通路。
SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation.
作者信息
Huang Lin, Gotoh Noriko, Zhang Shengliang, Shibuya Masabumi, Yamamoto Tadashi, Tsuchida Nobuo
机构信息
Department of Molecular Cellular Oncology and Microbiology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yujima, Bunkyo-ku, Tokyo 113-8510, Japan.
出版信息
Biochem Biophys Res Commun. 2004 Nov 19;324(3):1011-7. doi: 10.1016/j.bbrc.2004.09.152.
The control of cellular responses with fibroblast growth factors and neurotrophins is mediated through membrane-linked docking proteins, SNT (suc1-binding neurotrophic target)-1/FRS2alpha and SNT-2/FRS2beta. ERK1/2 are members of the mitogen-activated protein kinase family that regulate diverse cellular activities in response to various stimuli. Here, we demonstrate that SNT-2 does not become tyrosine phosphorylated significantly in response to EGF but forms a complex with ERK2 via the region of 186-252 amino acid residues, and the complex formation is enhanced upon EGF stimulation. SNT-2 downregulates ERK2 phosphorylation, suppresses and delays ERK2 nuclear accumulation which occurs following EGF stimulation. In contrast, the mutant SNT-2 which carries deletion of 186-252 amino acids and lacks ERK2 binding does not have these effects. These observations suggest that SNT-2 negatively regulates ERK2 signaling activated via EGF stimulation through direct binding to ERK2.
成纤维细胞生长因子和神经营养因子对细胞反应的控制是通过膜连接对接蛋白SNT（suc1结合神经营养靶标）-1/FRS2α和SNT-2/FRS2β介导的。ERK1/2是丝裂原活化蛋白激酶家族的成员，可响应各种刺激调节多种细胞活动。在此，我们证明SNT-2在响应表皮生长因子（EGF）时不会显著发生酪氨酸磷酸化，但通过186-252个氨基酸残基区域与ERK2形成复合物，且在EGF刺激后复合物形成增强。SNT-2下调ERK2磷酸化，抑制并延迟EGF刺激后发生的ERK2核积累。相反，携带186-252个氨基酸缺失且缺乏ERK2结合的突变型SNT-2没有这些作用。这些观察结果表明，SNT-2通过直接结合ERK2对EGF刺激激活的ERK2信号传导起负调节作用。
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