Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-1-5
pubmed:abstractText
Enhanced phosphorylation of the ribosomal protein s6 kinase, p70(s6k), and the translational repressor, 4E-BP1, are associated with either insulin-induced or amino acid-induced protein synthesis. Hyperphosphorylation of p70(s6k) and 4E-BP1 in response to insulin or amino acids is mediated through the mammalian target of rapamycin (mTOR). In several cell lines, mTOR or its downstream targets can be regulated by phosphatidylinositol (PI) 3-kinase; protein kinases A, B, and C; heterotrimeric G-proteins; a PD98059-sensitive kinase or calcium; as well as by amino acids. Regulation by amino acids appears to involve detection of levels of charged t-RNA or t-RNA synthetase activity and is sensitive to inhibition by amino acid alcohols. In the present article, however, we show that the rapamycin-sensitive regulation of 4E-BP1 and p70(s6k) in freshly isolated rat adipocytes is not inhibited by either L-leucinol or L-histidinol. This finding is in agreement with other recent studies from our laboratory suggesting that the mechanism by which amino acids regulate mTOR in freshly isolated adipocytes may be different than the mechanism found in a number of cell lines. Therefore we investigated the possible role of growth factor-regulated and G-protein-regulated signaling pathways in the rapamycin-sensitive, amino acid alcohol-insensitive actions of amino acids on 4E-BP1 phosphorylation. We found, in contrast to previously published results using 3T3-L1 adipocytes or other cell lines, that the increase in 4E-BP1 phosphorylation promoted by amino acids was insensitive to agents that regulate protein kinase A, mobilize calcium, or inhibit protein kinase C. Furthermore, amino acid-induced 4E-BP1 phosphorylation was not blocked by pertussis toxin nor was it mimicked by the G-protein agonists fluoroaluminate or MAS-7. However, amino acids failed to activate either PI 3-kinase, protein kinase B, or mitogen-activated protein kinase and failed to promote tyrosine phosphorylation of cellular proteins, similar to observations made using cell lines. In summary, amino acids appear to use an amino acid alcohol-insensitive mechanism to regulate mTOR in freshly isolated adipocytes. This mechanism is independent of cell-signaling pathways implicated in the regulation of mTOR or its downstream targets in other cells. Overall, our study emphasizes the need for caution when extending results obtained using established cell lines to the differentiated nondividing cells found in most tissues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate Ribose, http://linkedlifedata.com/resource/pubmed/chemical/Aluminum, http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Eif4ebp1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Fluorine, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha..., http://linkedlifedata.com/resource/pubmed/chemical/Histidinol, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Leucine, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group..., http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus, http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine, http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella, http://linkedlifedata.com/resource/pubmed/chemical/fluoroaluminum, http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, rat
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0730-2312
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
427-41
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10972980-Adenosine Diphosphate Ribose, pubmed-meshheading:10972980-Adipocytes, pubmed-meshheading:10972980-Aluminum, pubmed-meshheading:10972980-Amino Acids, pubmed-meshheading:10972980-Animals, pubmed-meshheading:10972980-Carrier Proteins, pubmed-meshheading:10972980-Cells, Cultured, pubmed-meshheading:10972980-Enzyme Inhibitors, pubmed-meshheading:10972980-Fluorine, pubmed-meshheading:10972980-GTP-Binding Protein alpha Subunits, Gi-Go, pubmed-meshheading:10972980-Histidinol, pubmed-meshheading:10972980-Insulin, pubmed-meshheading:10972980-Leucine, pubmed-meshheading:10972980-Male, pubmed-meshheading:10972980-Mitogen-Activated Protein Kinases, pubmed-meshheading:10972980-Pertussis Toxin, pubmed-meshheading:10972980-Phosphatidylinositol 3-Kinases, pubmed-meshheading:10972980-Phosphoproteins, pubmed-meshheading:10972980-Phosphorylation, pubmed-meshheading:10972980-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:10972980-Protein Kinases, pubmed-meshheading:10972980-Protein Processing, Post-Translational, pubmed-meshheading:10972980-Protein-Serine-Threonine Kinases, pubmed-meshheading:10972980-Proto-Oncogene Proteins, pubmed-meshheading:10972980-Proto-Oncogene Proteins c-akt, pubmed-meshheading:10972980-Rats, pubmed-meshheading:10972980-Rats, Sprague-Dawley, pubmed-meshheading:10972980-Ribosomal Protein S6 Kinases, pubmed-meshheading:10972980-Signal Transduction, pubmed-meshheading:10972980-Sirolimus, pubmed-meshheading:10972980-Staurosporine, pubmed-meshheading:10972980-TOR Serine-Threonine Kinases, pubmed-meshheading:10972980-Virulence Factors, Bordetella
pubmed:year
2000
pubmed:articleTitle
Assessment of cell-signaling pathways in the regulation of mammalian target of rapamycin (mTOR) by amino acids in rat adipocytes.
pubmed:affiliation
Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't