Grb14 inhibits FGF receptor signaling through the regulation of PLCγ recruitment and activation
Grb14 inhibits FGF receptor signaling through the regulation of PLCγ recruitment and activation
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DOI：
10.1016/j.febslet.2010.09.048
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发表时间：
2010-11-05
期刊：
影响因子：
3.5
通讯作者：
Burnol, Anne-Francoise
中科院分区：
文献类型：
--
作者：
Browaeys-Poly, Edith;Blanquart, Christophe;Burnol, Anne-Francoise
为了破解Grb14与活化的成纤维细胞生长因子受体（FGFR）结合的机制，我们使用了生物发光共振能量转移（BRET）技术和非洲爪蟾卵母细胞模型。我们发现Grb14被募集到FGFR1上，形成一个三聚体复合体，也含有磷脂酶C γ (PLC γ)。Grb14的存在改变了fgf诱导的PLC γ磷酸化和激活。Grb14-FGFR相互作用涉及Grb14-SH2结构域和FGFR pY766残基，后者是PLC γ结合位点。我们的数据导致了一个分子模型，其中Grb14结合磷酸化的FGFR诱导构象变化，揭示了Grb14上的PLC γ结合基序，允许PLC γ的捕获和失活。结构化摘要：MINT-8019680: Grb14 （uniprotkb:O88900）通过抗标签共免疫沉淀（MI: 0007）与FGFR1 （uniprotkb:P11362）物理相互作用（MI:0915） MINT-8019693, MINT-8019727: Grb14 （uniprotkb:O88900）通过生物发光共振能量转移（MI:0012）与FGFR1 （uniprotkb:P11362）物理相互作用（MI:0915） MINT-8019714, MINT-8019746: PLC gamma1 （uniprotkb:P19174）物理相互作用（MI:0915）与FGFR1 (uniprotkb:P11362) （uniprotkb:P11362）P11362)生物发光共振能量转移（MI: 0012） (C) 2010欧洲生化学会联合会。Elsevier B.V.版权所有。
To decipher the mechanism involved in Grb14 binding to the activated fibroblast growth factor receptor (FGFR), we used the bioluminescence resonance energy transfer (BRET) technique and the Xenopus oocyte model. We showed that Grb14 was recruited to FGFR1 into a trimeric complex containing also phospholipase C gamma (PLC gamma). The presence of Grb14 altered FGF-induced PLC gamma phosphorylation and activation. Grb14-FGFR interaction involved the Grb14-SH2 domain and the FGFR pY766 residue, which is the PLC gamma binding site. Our data led to a molecular model whereby Grb14 binding to the phosphorylated FGFR induces a conformational change that unmasks a PLC gamma binding motif on Grb14, allowing trapping and inactivation of PLC gamma.Structured summary:MINT-8019680: Grb14 (uniprotkb:O88900) physically interacts (MI:0915) with FGFR1 (uniprotkb:P11362) by anti tag coimmunoprecipitation (MI: 0007)MINT-8019693, MINT-8019727: Grb14 (uniprotkb:O88900) physically interacts (MI: 0915) with FGFR1 (uniprotkb: P11362) by bioluminescence resonance energy transfer (MI:0012)MINT-8019714, MINT-8019746: PLC gamma1 (uniprotkb:P19174) physically interacts (MI: 0915) with FGFR1 (uniprotkb: P11362) by bioluminescence resonance energy transfer (MI: 0012) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.