Mitra, PrasenjitZheng, XuexiuCzech, Michael P.2022-08-232022-08-232004-07-202008-08-04J Biol Chem. 2004 Sep 3;279(36):37431-5. Epub 2004 Jul 16. <a href="http://dx.doi.org/10.1074/jbc.C400180200">Link to article on publisher's site</a>0021-9258 (Print)10.1074/jbc.C40018020015258163https://hdl.handle.net/20.500.14038/42347Stimulation of glucose transport by insulin in cultured adipocytes through translocation of intracellular GLUT4 glucose transporters to the plasma membrane has been suggested to require phosphatidylinositol (PI) 3-kinase-dependent and independent mechanisms. To test the involvement of a PI 3-kinase-independent pathway leading to activation of the TC10 GTPase, the putative intermediates CAP, c-Cbl, Cbl-b, and CrkII were selectively depleted in 3T3-L1 adipocytes using highly efficient small interfering (si) RNAs. Simultaneous depletion of the ubiquitination factors c-Cbl plus Cbl-b in cultured adipocytes had the expected effect of delaying dephosphorylation of EGF receptors upon removal of EGF. However, siRNA-mediated gene silencing of both Cbl isoforms or CAP or CrkII in these cells failed to attenuate insulin-stimulated deoxyglucose transport or Myc-tagged GLUT4-GFP translocation at either sub-maximal or maximal concentrations of insulin. The dose-response relationship for insulin stimulation of deoxyglucose transport in primary adipocytes derived from c-Cbl knock-out mice was also identical to insulin action on adipocytes from wild type mice. These data are consistent with the hypothesis that CAP, Cbl iso-forms, and CrkII are not required components of insulin signaling to GLUT4 transporters.en-US3T3 CellsAnimalsCytoskeletal ProteinsGlucose Transporter Type 4InsulinMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-cblProto-Oncogene Proteins c-crk*RNA InterferenceUbiquitin-Protein LigasesLife SciencesMedicine and Health SciencesJournal Articlehttps://escholarship.umassmed.edu/oapubs/704564514oapubs/704