RagA, but not RagB, is essential for embryonic development and adult mice.
RagA, but not RagB, is essential for embryonic development and adult mice.
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DOI：
10.1016/j.devcel.2014.03.017
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发表时间：
2014-05-12
影响因子：
11.8
通讯作者：
Sabatini, David M.
中科院分区：
文献类型：
--
作者：
Efeyan, Alejo;Schweitzer, Lawrence D.;Bilate, Angelina M.;Chang, Steven;Kirak, Oktay;Lamming, Dudley W.;Sabatini, David M.
雷帕霉素复合体1的机制靶点是整合生长因子和营养物质的信号来控制新陈代谢。与生长因子的输入相反，哺乳动物中mTORC1依赖营养的激活的遗传干扰仍未被探索。我们改造了缺乏raga和ragB基因的小鼠，这两个基因编码的GTP酶负责通过营养激活mTORC1。RagB的表达是有限的，其缺失对哺乳动物的生理没有影响。RAGA缺乏会导致E10.5胚胎死亡、mTORC1活性丧失和严重的生长缺陷。来源于这些小鼠的原代细胞不受营养物质的调节，并对生长因子保持高度敏感。成年小鼠中raga基因的缺失是致命的。当RAGA丢失时，周围组织中的髓系群体扩大。肝脏中RAGA特异性缺失增加了细胞对生长因子的反应。这些结果表明了营养传感对小鼠mTORC1活性及其对PI3K/Akt信号通路的抑制的重要性。
The mechanistic target of rapamycin complex 1 (mTORC1) integrates cues from growth factors and nutrients to control metabolism. In contrast to the growth factor input, genetic disruption of nutrient-dependent activation of mTORC1 in mammals remains unexplored. We engineered mice lacking RagA and RagB genes, which encode the GTPases responsible for mTORC1 activation by nutrients. RagB has limited expression and its loss shows no effects on mammalian physiology. RagA deficiency leads to E10.5 embryonic death, loss of mTORC1 activity, and severe growth defects. Primary cells derived from these mice exhibit no regulation of mTORC1 by nutrients, and maintain high sensitivity to growth factors. Deletion of RagA in adult mice is lethal. Upon RagA loss, a myeloid population expands in peripheral tissues. RagA-specific deletion in liver increases cellular responses to growth factors. These results show the essentiality of nutrient sensing for mTORC1 activity in mice and its suppression of PI3K/Akt signalling.
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影响因子：
3.7
作者：
Groenewoud MJ;Goorden SM;Kassies J;Pellis-van Berkel W;Lamb RF;Elgersma Y;Zwartkruis FJ
通讯作者：
Zwartkruis FJ
P14-MP1-MEK1信号传导调节组织稳态期间的内体流量和细胞增殖。
影响因子：
7.8
作者：
Teis, David;Taub, Nicole;Kurzbauer, Robert;Hilber, Diana;de Araujo, Mariana E.;Erlacher, Miriam;Offterdinger, Martin;Villunger, Andreas;Geley, Stephan;Bohn, Georg;Klein, Christoph;Hess, Michael W.;Huber, Lukas A.
通讯作者：
Huber, Lukas A.
DOI：
10.1083/jcb.200403069
发表时间：
2004-07-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Harrington LS;Findlay GM;Gray A;Tolkacheva T;Wigfield S;Rebholz H;Barnett J;Leslie NR;Cheng S;Shepherd PR;Gout I;Downes CP;Lamb RF
通讯作者：
Lamb RF
影响因子：
7.5
作者：
Polak, Pazit;Hall, Michael N.
通讯作者：
Hall, Michael N.
影响因子：
5.3
作者：
Goorden, Susanna M. I.;Hoogeveen-Westerveld, Marianne;Elgersma, Ype
通讯作者：
Elgersma, Ype