Roles of mTOR and JNK in serine phosphorylation, translocation, and degradation of IRS-1

Biochem Biophys Res Commun. 2005 Sep 30;335(3):836-42. doi: 10.1016/j.bbrc.2005.07.152.

Abstract

In 3T3-L1 adipocytes, insulin or anisomycin stimulated phosphorylation of IRS-1 at Ser(307) and Ser(636/639), both of which were partially reduced by the mTOR inhibitor, rapamycin, or the JNK inhibitor, SP600125, and were further inhibited by a combination of them. Interestingly, anisomycin-induced p70(S6K) phosphorylation was reduced by SP600125, while insulin-induced p70(S6K) phosphorylation was not. Furthermore, unlike insulin, anisomycin failed to elicit translocation or degradation of IRS-1. These results indicate that mTOR and JNK play roles in phosphorylating IRS-1 serine residues, and that insulin and anisomycin are different in terms of the relationship of activation between mTOR and JNK, and the effects on IRS-1 localization and stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Anisomycin / pharmacology
  • Hydrolysis
  • Insulin Receptor Substrate Proteins
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Kinase 4
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Protein Transport
  • Serine / metabolism*
  • TOR Serine-Threonine Kinases

Substances

  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Phosphoproteins
  • Serine
  • Anisomycin
  • Protein Kinases
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases