同样的,在缺乏氨基酸或者生长因子的环境下敲低Rag GTPase也会恢复TORC1的活性。这些实验表明在营养受限的条件下,Rag GTPase从TORC1 的激活物变成抑制物。 德国癌症研究中心的Teleman 研究组在2014以HEK293T细胞为模型时发现,切断细胞的氨...
同时,还发现在缺乏氨基酸的情况下,GPR137B的过表达仍然能激活Rag;而GPR137B敲低可影响Rag对mTORC1的激活,进一步提示该蛋白对Rag A有直接调控作用。 RagGTPase A活化相应激活了mTORC1的溶酶体定位和活化。同时,作者还发现随着mTORC1溶酶...
The nutrient-sensing Rag-GTPase complex in B cells controls humoral immunity via TFEB/TFE3-dependent mitochondrial fitnessGerminal center (GC) formation, which is an integrant part of humoral immunity, involves energy-consuming metabolic reprogramming. Rag-GTPases are known to signal amino acid ...
Amino acid availability controls mTORC1 activity via a heterodimeric Rag GTPase complex that functions as a scaffold at the lysosomal surface, bringing together mTORC1 with its activators and effectors. Mammalian cells express four Rag proteins (RagA–D) that form dimers composed of RagA/B bound to...
Structural mechanism for amino acid-dependent Rag GTPase switching by SLC38A9The Rag GTPases (Rags) recruit mTORC1 to the lysosomal membrane in response to nutrients, where it is then activated in response to energy and growth factor availability. The lysosomal folliculin (FLCN) complex (LFC) ...
Our recent study demonstrated that the fission yeast Schizosaccharomyces pombe also has a Ragulator complex that anchors the Gtr1-Gtr2 Rag GTPase heterodimer to the vacuole, a lysosome-like organelle. Unexpectedly, however, neither vacuolar localization nor activation of TORC1 is...
Rag GTPasesnutrientsB cellslymphomasmall moleculesmiceThe identification of the Rag GTPases initiated the deciphering of the molecular puzzle of nutrient signaling to the mechanistic target of rapamycin (mTOR), and spurred interest in targeting this pathway to combat human disease. Recent mouse ...
This is a mechanism driving changes in excitability of nociceptors that is critical for the generation of chronic pain states; however, the mRNAs that are translated to lead to this plasticity have not been elucidated. To address this gap in knowledge, we used transl...
Oncogenic Rag GTPase signalling enhances B cell activation and drives follicular lymphoma sensitive to pharmacological inhibition of mTORThe humoral immune response requires that B cells undergo a sudden anabolic shift and high cellular nutrient levels, which are required to sustain the subsequent ...
Keywords: Crystal structure; EGO complex; Rag GTPase; TORC1 signaling; growth control Cell Research (2015) 25:1043-1059. doi:10.1038/cr.2015.86; published online 24 July 2015 Introduction The target of rapamycin complex 1 (TORC1) is a highly conserved protein kinase complex that couples a ...