Role of IRS-1 and SHC activation in 3T3-L1 fibroblasts differentiation.
The early steps of 3T3-L1 fibroblasts differentiation to adipocytes are characterized by a proliferation phase, termed clonal expansion, that ends after the first 48 h of exposure of confluent cells to high doses of insulin, dexamethasone, 3-methyl-isobutylxanthine and FCS (differentiation mix). Since insulin is a key hormone for adipocyte conversion, and IRS-1 (insulin receptor substrate -1) and Shc (Src homology collagen)-proximal intracellular substrates of the insulin receptor-control cell proliferation, the aim of this study was to investigate the role of IRS-1 and Shc in the early steps of differentiation. At the end of clonal expansion, 48 h after induction of differentiation with differentiation mix, p66 Shc phosphorylation and IRS-1 amounts were reduced in those cells committed to fully differentiate. Conversely, in cells treated with insulin alone or dexamethasone alone (unable to be differentiated), p66 Shc and IRS-1 activities were maintained unaltered, compared to basal values. These observations suggest that the modifications of p66 Shc and IRS-1 in the first 48 h of 3T3-L1 conversion into adipocytes could play a role on this process, or alternatively they could represent an early cellular marker of differentiation.
Laurino
C
C
Di. S.E.M., University of Genova, Italy.
Cordera
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D003907:Dexamethasone; D019869:Phosphatidylinositol 3-Kinases; D015056:1-Methyl-3-isobutylxanthine