LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein.
LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein.
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DOI：
10.1242/jcs.222257
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发表时间：
2018-09-20
影响因子：
4
通讯作者：
Burdon T
中科院分区：
文献类型：
--
作者：
Sutherland L;Ruhe M;Gattegno-Ho D;Mann K;Greaves J;Koscielniak M;Meek S;Lu Z;Waterfall M;Taylor R;Tsakiridis A;Brown H;Maciver SK;Joshi A;Clinton M;Chamberlain LH;Smith A;Burdon T
细胞因子白血病抑制因子 (LIF) 通过激活转录因子 Stat3 促进小鼠胚胎干细胞 (ESC) 的自我更新。然而，ESC 中 LIF 刺激的其他辅助途径（例如 MAPK 和 PI3K 途径）的贡献尚不清楚。我们在此表明，幼稚型小鼠 ESC 表达高水平的 MAPK 和 PI3K 途径的新型效应子。该效应子是 Gab1（Grb2 相关结合蛋白 1）衔接蛋白的同种型，缺乏 N 端 pleckstrin 同源 (PH) 膜结合域。虽然新的 Gab1 变体 (Gab1β) 对于 ESC 在最佳条件下快速无限制生长不是必需的，但它是 LIF 介导的细胞在营养供应有限的条件下生存所必需的。这种存活率的提高绝对依赖于直接将 Gab1β 靶向 ESC 膜的潜在棕榈酰化位点。这些结果表明，Gab1 通过一种新机制与细胞膜的组成性关联可促进小鼠 ESC 在营养不良的条件下依赖 LIF 的存活。 胚胎干细胞依靠新型脂质修饰 Gab1 接头蛋白的表达来促进营养不良条件下的存活。
The cytokine leukaemia inhibitory factor (LIF) promotes self-renewal of mouse embryonic stem cells (ESCs) through activation of the transcription factor Stat3. However, the contribution of other ancillary pathways stimulated by LIF in ESCs, such as the MAPK and PI3K pathways, is less well understood. We show here that naive-type mouse ESCs express high levels of a novel effector of the MAPK and PI3K pathways. This effector is an isoform of the Gab1 (Grb2-associated binder protein 1) adaptor protein that lacks the N-terminal pleckstrin homology (PH) membrane-binding domain. Although not essential for rapid unrestricted growth of ESCs under optimal conditions, the novel Gab1 variant (Gab1β) is required for LIF-mediated cell survival under conditions of limited nutrient availability. This enhanced survival is absolutely dependent upon a latent palmitoylation site that targets Gab1β directly to ESC membranes. These results show that constitutive association of Gab1 with membranes through a novel mechanism promotes LIF-dependent survival of murine ESCs in nutrient-poor conditions. Embryonic stem cells rely upon expression of a novel lipid-modified Gab1 adaptor protein to promote survival under nutrient-poor conditions.
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影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
5.9
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Guo G;von Meyenn F;Santos F;Chen Y;Reik W;Bertone P;Smith A;Nichols J
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Nichols J
影响因子：
64.8
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Bulut-Karslioglu, Aydan;Biechele, Steffen;Jin, Hu;Macrae, Trisha A.;Hejna, Miroslav;Gertsenstein, Marina;Song, Jun S.;Ramalho-Santos, Miguel
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Ramalho-Santos, Miguel
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
4.6
作者：
Guo, Ge;Yang, Jian;Smith, Austin
通讯作者：
Smith, Austin