Insulin stimulates mitogen-activated protein kinase by a Ras-independent pathway in 3T3-L1 adipocytes.

The Journal of Biological Chemistry
K CarelB Draznin

Abstract

To characterize tissue-specific differences in insulin signaling, we compared the mechanisms of mitogen-activated protein (MAP) kinase activation by insulin in the mitogenically active 3T3-L1 fibroblasts with the metabolically active 3T3-L1 adipocytes. In both cell lines, insulin significantly increased p21(ras).GTP loading (1.5-2-fold) and MAP kinase activity (5-8-fold). Inhibition of Ras farnesylation with lovastatin blocked activation of p21(ras) and Raf-1 kinase in both 3T3-L1 fibroblasts and 3T3-L1 adipocytes. In 3T3-L1 fibroblasts, this was accompanied by an inhibition of the stimulatory effect of insulin on MAP kinase. In contrast, in 3T3-L1 adipocytes, despite an inhibition of activation of p21(ras) and Raf-1 by lovastatin, insulin continued to stimulate MAP kinase activity. Fractionation of the cell lysates on the FPLC Mono-Q column revealed that lovastatin inhibited insulin stimulation of ERK2 (and, to a lesser extent, ERK1) in 3T3-L1 fibroblasts and had no effect on the insulin-stimulated ERK2 in 3T3-L1 adipocytes. These results demonstrate an important distinction between the mechanism of insulin signaling in the metabolically and mitogenically active cells. Insulin activates MAP kinase by the Ras-dependent pathway ...Continue Reading

References

Jul 30, 1992·Nature·J M KyriakisJ Avruch
May 26, 1995·The Journal of Biological Chemistry·G ZhouJ E Dixon
Apr 1, 1995·Endocrine Reviews·B Cheatham, C R Kahn
Jun 23, 1995·The Journal of Biological Chemistry·M H Cobb, E J Goldsmith
Feb 3, 1995·The Journal of Biological Chemistry·J E ReuschB Draznin
Nov 1, 1994·Trends in Biochemical Sciences·G DaumU R Rapp
Sep 2, 1994·Science·C A Lange-Carter, G L Johnson
Jun 1, 1994·Trends in Biochemical Sciences·K J Blumer, G L Johnson
Feb 9, 1996·The Journal of Biological Chemistry·J HanR J Ulevitch
Jun 28, 1996·The Journal of Biological Chemistry·C SchubertB Draznin

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Citations

Mar 19, 1999·Journal of Cellular Physiology·R G JainP H Pekala
Nov 26, 2008·BMC Biochemistry·Simon S Wing
Apr 29, 1998·Molecular Neurobiology·K Fukunaga, E Miyamoto
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Jan 18, 2003·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·C S SolomonM L Goalstone
May 20, 2008·The Journal of Biological Chemistry·Lise MadsenKarsten Kristiansen
Jan 13, 2006·European Journal of Cell Biology·Lunhua LiuLiguang Lou
May 26, 2006·Journal of Cell Science·Linda AnderssonSven-Olof Olofsson

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