SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation
SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation
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DOI：
10.1016/j.bbrc.2004.09.152
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发表时间：
2004-11-19
影响因子：
3.1
通讯作者：
Tsuchida, N
中科院分区：
文献类型：
--
作者：
Huang, L;Gotoh, N;Tsuchida, N
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的对接蛋白SNT（sucl结合神经营养靶标）-1/FRS2 β和SNT-2/FRS 2 β介导的。ERKI/2是丝裂原活化蛋白激酶家族的成员，其调节响应于各种刺激的多种细胞活性。在这里，我们证明，SNT-2不会成为酪氨酸磷酸化显着响应EGF，但形成一个复合物与ERK 2通过186-252个氨基酸残基的区域，和复合物的形成增强EGF刺激。SNT-2下调ERK 2磷酸化，抑制和延迟EGF刺激后发生的ERK 2核积累。相反，携带186-252个氨基酸缺失且缺乏ERK 2结合的突变体SNT-2不具有这些作用。这些观察结果表明，SNT-2通过直接结合ERK 2，负调节通过EGF刺激激活的ERK 2信号传导。(C)2004年由Elsevier Inc.出版
The control of cellular responses with fibroblast growth factors and neurotrophins is mediated through membrane-linked docking proteins, SNT (sucl-binding neurotrophic target)- 1/FRS2beta and SNT-2/FRS2beta. ERKI/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 lack i 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. (C) 2004 Published by Elsevier Inc.