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LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Gan, Wenjian[1,2] * ; Dai, Xiaoming[1] ; Dai, Xiangpeng[1] ; Xie, Jun[3,4,5] ; Yin, Shasha[2] ; Zhu, Junjie[6,7] ; Wang, Chen[6,7] ; Liu, Yuchen[8] ; Guo, Jianping[1] ; Wang, Min[1,9] ; Liu, Jing[1] ; Hu, Jia[1,10] ; Quinton, Ryan J.[11,12] ; Ganem, Neil J.[11,12] ; Liu, Pengda[13] ; Asara, John M.[14,15] ; Pandolfi, Pier Paolo[16] ; Yang, Yingzi[8] ; He, Zhigang[6,7] ; Gao, Guangping[3,4,5] ; Wei, Wenyi[1] ;
单位： [1]Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA [2]Med Univ South Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA [3]Univ Massachusetts, Sch Med, Li Weibo Inst Rare Dis Res, Worcester, MA USA [4]Univ Massachusetts, Sch Med, Horae Gene Therapy Ctr, Worcester, MA USA [5]Univ Massachusetts, Sch Med, Vector Core, Worcester, MA USA [6]Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA USA [7]Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA [8]Harvard Sch Dent Med, Harvard Stem Cell Inst, Dept Dev Biol, Boston, MA USA [9]Huazhong Univ Sci & Technol,Affiliated Tongji Hosp,Dept Biliary Pancreat Surg,Tongji Med Coll,Wuhan,Peoples R China [10]Huazhong Univ Sci & Technol,Affiliated Tongji Hosp,Dept Urol,Tongji Med Coll,Wuhan,Peoples R China [11]Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Canc Cell Biol Lab, Boston, MA 02118 USA [12]Boston Univ, Sch Med, Dept Med, Div Hematol & Oncol, Boston, MA 02118 USA [13]Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27515 USA [14]Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA [15]Harvard Med Sch, Dept Med, Boston, MA 02115 USA [16]Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol & Med, Canc Res Inst, Boston, MA 02115 USA
出处：
DOI： 10.1038/s41556-020-0463-6
ISSN：

摘要：
The Hippo and mTORC1 pathways regulate growth control for proper organ development. Here, Gan et al. find that the Hippo pathway kinases LATS1 and LATS2 phosphorylate the mTORC1 component Raptor to attenuate mTORC1 activation. The Hippo and mammalian target of rapamycin complex 1 (mTORC1) pathways are the two predominant growth-control pathways that dictate proper organ development. We therefore explored potential crosstalk between these two functionally relevant pathways to coordinate their growth-control functions. We found that the LATS1 and LATS2 kinases, the core components of the Hippo pathway, phosphorylate S606 of Raptor, an essential component of mTORC1, to attenuate mTORC1 activation by impairing the interaction of Raptor with Rheb. The phosphomimetic Raptor-S606D knock-in mutant led to a reduction in cell size and proliferation. Compared with Raptor(+/+) mice, Raptor(D/D) knock-in mice exhibited smaller livers and hearts, and a significant inhibition of elevation in mTORC1 signalling induced by Nf2 or Lats1 and Lats2 loss. Thus, our study reveals a direct link between the Hippo and mTORC1 pathways to fine-tune organ growth.

基金：
NRSA T-32 training grants; National Cancer Institute [R00CA181342]; NCI [R01CA222571]; NIH [R00CA207867, R01GM094777, R01CA177910, P30EY012196, P01CA120964, P30CA006516]; MUSC Digestive Diseases Research Core Center Pilot and Feasibility Program
语种：
外文
被引次数：
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中科院(CAS)分区：
出版当年[2019]版：
大类 | 1 区 生物
小类 | 1 区 细胞生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 1 区 细胞生物学
JCR分区：
出版当年[2018]版：
Q1 CELL BIOLOGY
最新[2023]版：
Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

第一作者：
第一作者单位： [1]Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA [2]Med Univ South Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA
通讯作者：
通讯机构： [1]Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA [2]Med Univ South Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA
推荐引用方式(GB/T 7714)：
Gan Wenjian,Dai Xiaoming,Dai Xiangpeng,et al.LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control[J].NATURE CELL BIOLOGY.2020,22(2):246-+.doi:10.1038/s41556-020-0463-6.
APA：
Gan, Wenjian,Dai, Xiaoming,Dai, Xiangpeng,Xie, Jun,Yin, Shasha...&Wei, Wenyi.(2020).LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control.NATURE CELL BIOLOGY,22,(2)
MLA：
Gan, Wenjian,et al."LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control".NATURE CELL BIOLOGY 22..2(2020):246-+

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