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10.1172/JCI89452 http://scihub22266oqcxt.onion/10.1172/JCI89452 C5373863!5373863 !28319048     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28319048 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Clin+Invest 2017 ; 127 (4 ): 1405-1413 Nephropedia Template TP {{tp|p=28319048 |t=2017. Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells |pdf=|usr=}}{{28319048 }} gab.com Text Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells JO: J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=28319048 #FOAvip The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity. Here, we have evaluated differential nutrient-sensing dependence through RagA and mTORC1 in hematopoietic progenitors, which dynamically drive mature cell production, and hematopoietic stem cells (HSC), which provide a quiescent cellular reserve. In nutrient-abundant conditions, RagA-deficient HSC were functionally unimpaired and upregulated mTORC1 via nutrient-insensitive mechanisms. RagA was also dispensable for HSC function under nutritional stress conditions. Similarly, hyperactivation of RagA did not affect HSC function. In contrast, RagA deficiency markedly altered progenitor population function and mature cell output. Therefore, RagA is a molecular mechanism that distinguishes the functional attributes of reactive progenitors from a reserve stem cell pool. The indifference of HSC to nutrient sensing through RagA contributes to their molecular resilience to nutritional stress, a characteristic that is relevant to organismal viability in evolution and in modern HSC transplantation approaches. Twit Text FOAVip Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells ????J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=28319048 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28319048 #FOAvip English Wikipedia <ref>{{Cite pmid|28319048 }}</ref> Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells #MMPMID28319048 Kalaitzidis D ; Lee D ; Efeyan A ; Kfoury Y ; Nayyar N ; Sykes DB ; Mercier FE ; Papazian A ; Baryawno N ; Victora GD ; Neuberg D ; Sabatini DM ; Scadden DT J Clin Invest 2017[Apr]; 127 (4 ): 1405-1413 PMID28319048 show ga The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity. Here, we have evaluated differential nutrient-sensing dependence through RagA and mTORC1 in hematopoietic progenitors, which dynamically drive mature cell production, and hematopoietic stem cells (HSC), which provide a quiescent cellular reserve. In nutrient-abundant conditions, RagA-deficient HSC were functionally unimpaired and upregulated mTORC1 via nutrient-insensitive mechanisms. RagA was also dispensable for HSC function under nutritional stress conditions. Similarly, hyperactivation of RagA did not affect HSC function. In contrast, RagA deficiency markedly altered progenitor population function and mature cell output. Therefore, RagA is a molecular mechanism that distinguishes the functional attributes of reactive progenitors from a reserve stem cell pool. The indifference of HSC to nutrient sensing through RagA contributes to their molecular resilience to nutritional stress, a characteristic that is relevant to organismal viability in evolution and in modern HSC transplantation approaches. |Adaptation, Physiological [MESH] |Amino Acids/physiology [MESH] |Animals [MESH] |Cell Differentiation [MESH] |Cells, Cultured [MESH] |Hematopoietic Stem Cells/*physiology [MESH] |Homeostasis [MESH] |Mechanistic Target of Rapamycin Complex 1 [MESH] |Mice, Inbred C57BL [MESH] |Mice, Transgenic [MESH] |Monomeric GTP-Binding Proteins/metabolism [MESH] |Multiprotein Complexes/*metabolism [MESH] |Stress, Physiological [MESH]Amino acid-insensitive mTORC1 regulation enables nutritional stress re(epmc).pdf DeepDyve Pubget Overpricing