signaling complex / GTPase / lysosome / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / regulation of cholesterol efflux / Gtr1-Gtr2 GTPase complex / FNIP-folliculin RagC/D GAP / Ragulator complex / positive regulation of pentose-phosphate shunt / regulation of TORC1 signaling / positive regulation of odontoblast differentiation ...regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / regulation of cholesterol efflux / Gtr1-Gtr2 GTPase complex / FNIP-folliculin RagC/D GAP / Ragulator complex / positive regulation of pentose-phosphate shunt / regulation of TORC1 signaling / positive regulation of odontoblast differentiation / TORC1 complex / protein localization to lysosome / lysosome localization / Energy dependent regulation of mTOR by LKB1-AMPK / cellular response to L-leucine / Amino acids regulate mTORC1 / endosome organization / Dengue virus modulates apoptosis / positive regulation of osteoclast differentiation / TORC1 signaling / cellular response to osmotic stress / MTOR signalling / kinase activator activity / protein localization to membrane / lysosome organization / regulation of cell size / azurophil granule membrane / endosomal transport / regulation of TOR signaling / Macroautophagy / small GTPase-mediated signal transduction / RHOJ GTPase cycle / RHOQ GTPase cycle / positive regulation of transcription by RNA polymerase III / response to amino acid / CDC42 GTPase cycle / regulation of receptor recycling / social behavior / tertiary granule membrane / RHOG GTPase cycle / TOR signaling / RHOH GTPase cycle / mTORC1-mediated signalling / RAC3 GTPase cycle / HSF1-dependent transactivation / ficolin-1-rich granule membrane / RAC2 GTPase cycle / positive regulation of TOR signaling / enzyme-substrate adaptor activity / positive regulation of lipid biosynthetic process / protein kinase activator activity / protein serine/threonine kinase inhibitor activity / specific granule membrane / positive regulation of G1/S transition of mitotic cell cycle / cellular response to nutrient levels / RNA splicing / positive regulation of endothelial cell proliferation / cholesterol homeostasis / RAC1 GTPase cycle / 14-3-3 protein binding / protein-membrane adaptor activity / positive regulation of TORC1 signaling / guanyl-nucleotide exchange factor activity / positive regulation of glycolytic process / negative regulation of autophagy / viral genome replication / cellular response to amino acid starvation / cellular response to amino acid stimulus / cellular response to starvation / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / positive regulation of interleukin-8 production / TP53 Regulates Metabolic Genes / cellular response to glucose stimulus / regulation of cell growth / phosphoprotein binding / positive regulation of protein localization to nucleus / MAP2K and MAPK activation / response to virus / small GTPase binding / intracellular protein localization / cytoplasmic stress granule / GDP binding / glucose homeostasis / late endosome / late endosome membrane / positive regulation of cell growth / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / cellular response to hypoxia / molecular adaptor activity / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / positive regulation of MAPK cascade / positive regulation of canonical NF-kappaB signal transduction / lysosome / protein-macromolecule adaptor activity / intracellular signal transduction / response to xenobiotic stimulus / endosome membrane / apoptotic process 類似検索 - 分子機能
Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / LAMTOR1/MEH1 / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / RagA/B ...Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / LAMTOR1/MEH1 / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / RagA/B / RagC/D / Gtr1/RagA G protein / Gtr1/RagA G protein conserved region / Raptor, N-terminal CASPase-like domain / Ragulator complex protein LAMTOR2-like / Raptor N-terminal CASPase like domain / Raptor N-terminal CASPase like domain / Regulatory associated protein of TOR / HEAT repeat / Roadblock/LAMTOR2 domain / Roadblock/LC7 domain / Roadblock/LC7 domain / HEAT repeat / Armadillo-like helical / WD domain, G-beta repeat / Armadillo-type fold / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Ragulator complex protein LAMTOR5 / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR1 / Ras-related GTP-binding protein A / Regulatory-associated protein of mTOR / Ras-related GTP-binding protein C / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR2 類似検索 - 構成要素
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01 CA103866
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01 CA129105
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R37 AI47389
米国
Department of Defense (DOD, United States)
W81XWH-07-0448
米国
Lustgarten Foundation
米国
Tuberous Sclerosis Association
英国
Howard Hughes Medical Institute (HHMI)
米国
American Cancer Society
米国
引用
ジャーナル: Science / 年: 2019 タイトル: Structural basis for the docking of mTORC1 on the lysosomal surface. 著者: Kacper B Rogala / Xin Gu / Jibril F Kedir / Monther Abu-Remaileh / Laura F Bianchi / Alexia M S Bottino / Rikke Dueholm / Anna Niehaus / Daan Overwijn / Ange-Célia Priso Fils / Sherry X Zhou ...著者: Kacper B Rogala / Xin Gu / Jibril F Kedir / Monther Abu-Remaileh / Laura F Bianchi / Alexia M S Bottino / Rikke Dueholm / Anna Niehaus / Daan Overwijn / Ange-Célia Priso Fils / Sherry X Zhou / Daniel Leary / Nouf N Laqtom / Edward J Brignole / David M Sabatini / 要旨: The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where ...The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where its Raptor subunit interacts with the Rag guanosine triphosphatase (GTPase)-Ragulator complex. Nutrients switch the heterodimeric Rag GTPases among four different nucleotide-binding states, only one of which (RagA/B•GTP-RagC/D•GDP) permits mTORC1 association. We used cryo-electron microscopy to determine the structure of the supercomplex of Raptor with Rag-Ragulator at a resolution of 3.2 angstroms. Our findings indicate that the Raptor α-solenoid directly detects the nucleotide state of RagA while the Raptor "claw" threads between the GTPase domains to detect that of RagC. Mutations that disrupted Rag-Raptor binding inhibited mTORC1 lysosomal localization and signaling. By comparison with a structure of mTORC1 bound to its activator Rheb, we developed a model of active mTORC1 docked on the lysosome.