| http://purl.uniprot.org/citations/23263183 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23263183 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23263183 | http://www.w3.org/2000/01/rdf-schema#comment | "The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates organismal growth in response to many environmental cues, including nutrients and growth factors. Cell-based studies showed that mTORC1 senses amino acids through the RagA-D family of GTPases (also known as RRAGA, B, C and D), but their importance in mammalian physiology is unknown. Here we generate knock-in mice that express a constitutively active form of RagA (RagA(GTP)) from its endogenous promoter. RagA(GTP/GTP) mice develop normally, but fail to survive postnatal day 1. When delivered by Caesarean section, fasted RagA(GTP/GTP) neonates die almost twice as rapidly as wild-type littermates. Within an hour of birth, wild-type neonates strongly inhibit mTORC1, which coincides with profound hypoglycaemia and a decrease in plasma amino-acid concentrations. In contrast, mTORC1 inhibition does not occur in RagA(GTP/GTP) neonates, despite identical reductions in blood nutrient amounts. With prolonged fasting, wild-type neonates recover their plasma glucose concentrations, but RagA(GTP/GTP) mice remain hypoglycaemic until death, despite using glycogen at a faster rate. The glucose homeostasis defect correlates with the inability of fasted RagA(GTP/GTP) neonates to trigger autophagy and produce amino acids for de novo glucose production. Because profound hypoglycaemia does not inhibit mTORC1 in RagA(GTP/GTP) neonates, we considered the possibility that the Rag pathway signals glucose as well as amino-acid sufficiency to mTORC1. Indeed, mTORC1 is resistant to glucose deprivation in RagA(GTP/GTP) fibroblasts, and glucose, like amino acids, controls its recruitment to the lysosomal surface, the site of mTORC1 activation. Thus, the Rag GTPases signal glucose and amino-acid concentrations to mTORC1, and have an unexpectedly key role in neonates in autophagy induction and thus nutrient homeostasis and viability."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature11745"xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature11745"xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Chang S."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Chang S."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Sabatini D.M."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Sabatini D.M."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Sabatini D.D."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Sabatini D.D."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Wolfson R.L."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Wolfson R.L."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Zoncu R."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Zoncu R."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Efeyan A."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Efeyan A."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Gumper I."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Gumper I."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Kirak O."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Kirak O."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Snitkin H."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/author | "Snitkin H."xsd:string |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23263183 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |