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dc.contributor.authorKozma, Lynn M.
dc.contributor.authorBaltensperger, Kurt
dc.contributor.authorKlarlund, Jes K.
dc.contributor.authorPorras, A
dc.contributor.authorSantos, E
dc.contributor.authorCzech, Michael P.
dc.date2022-08-11T08:09:36.000
dc.date.accessioned2022-08-23T16:37:19Z
dc.date.available2022-08-23T16:37:19Z
dc.date.issued1993-05-15
dc.date.submitted2009-04-02
dc.identifier.citation<p>Proc Natl Acad Sci U S A. 1993 May 15;90(10):4460-4.</p>
dc.identifier.issn0027-8424 (Print)
dc.identifier.pmid8389451
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38988
dc.description.abstractRecent observations suggest that insulin increases cellular levels of activated, GTP-bound Ras protein. We tested whether the acute actions of insulin on hexose uptake and glucose-transporter redistribution to the cell surface are mimicked by activated Ras. 3T3-L1 fibroblasts expressing an activated mutant (Lys-61) N-Ras protein exhibited a 3-fold increase in 2-deoxyglucose uptake rates compared with non-transfected cells. Insulin stimulated hexose uptake by approximately 2-fold in parental fibroblasts but did not stimulate hexose uptake in the N-Ras61K-expressing fibroblasts. Overexpression of N-Ras61K also mimicked the large effect of insulin on 2-deoxyglucose transport in 3T3-L1 adipocytes, and again the effects of the two agents were not additive. Total glucose transporter protein (GLUT) 1 was similar between parental and N-Ras61K-expressing 3T3-L1 fibroblasts or adipocytes, whereas total GLUT-4 protein was actually lower in the N-Ras61K-expressing compared with parental adipocytes. However, expression of N-Ras61K in 3T3-L1 adipocytes markedly elevated both GLUT-1 and GLUT-4 in plasma membranes relative to intracellular membranes, and insulin had no further effect. These modulations of glucose transporters by N-Ras61K expression are not due to upstream regulation of insulin receptors because receptor tyrosine phosphorylation and association of phosphatidylinositol 3-kinase with tyrosine-phosphorylated proteins were unaffected. These results show that activated Ras mimics the actions of insulin on membrane trafficking of glucose transporters, consistent with the concept that Ras proteins function as intermediates in this insulin signaling pathway.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=8389451&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC46531/
dc.subject1-Phosphatidylinositol 3-Kinase
dc.subject3T3 Cells
dc.subjectAnimals
dc.subjectBiological Transport
dc.subjectCell Membrane
dc.subjectDeoxyglucose
dc.subjectGlucose
dc.subjectInsulin
dc.subjectMice
dc.subjectMonosaccharide Transport Proteins
dc.subjectPhosphotransferases
dc.subjectProto-Oncogene Proteins p21(ras)
dc.subjectReceptor, Insulin
dc.subjectSignal Transduction
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleThe ras signaling pathway mimics insulin action on glucose transporter translocation
dc.typeArticle
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume90
dc.source.issue10
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1815
dc.identifier.contextkey808581
html.description.abstract<p>Recent observations suggest that insulin increases cellular levels of activated, GTP-bound Ras protein. We tested whether the acute actions of insulin on hexose uptake and glucose-transporter redistribution to the cell surface are mimicked by activated Ras. 3T3-L1 fibroblasts expressing an activated mutant (Lys-61) N-Ras protein exhibited a 3-fold increase in 2-deoxyglucose uptake rates compared with non-transfected cells. Insulin stimulated hexose uptake by approximately 2-fold in parental fibroblasts but did not stimulate hexose uptake in the N-Ras61K-expressing fibroblasts. Overexpression of N-Ras61K also mimicked the large effect of insulin on 2-deoxyglucose transport in 3T3-L1 adipocytes, and again the effects of the two agents were not additive. Total glucose transporter protein (GLUT) 1 was similar between parental and N-Ras61K-expressing 3T3-L1 fibroblasts or adipocytes, whereas total GLUT-4 protein was actually lower in the N-Ras61K-expressing compared with parental adipocytes. However, expression of N-Ras61K in 3T3-L1 adipocytes markedly elevated both GLUT-1 and GLUT-4 in plasma membranes relative to intracellular membranes, and insulin had no further effect. These modulations of glucose transporters by N-Ras61K expression are not due to upstream regulation of insulin receptors because receptor tyrosine phosphorylation and association of phosphatidylinositol 3-kinase with tyrosine-phosphorylated proteins were unaffected. These results show that activated Ras mimics the actions of insulin on membrane trafficking of glucose transporters, consistent with the concept that Ras proteins function as intermediates in this insulin signaling pathway.</p>
dc.identifier.submissionpathoapubs/1815
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages4460-4


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