Retinoblastoma protein phosphorylation via PI 3-kinase and mTOR pathway regulates adipocyte differentiation

Biochem Biophys Res Commun. 2000 Aug 18;275(1):115-20. doi: 10.1006/bbrc.2000.3201.

Abstract

In the early phase of adipocyte differentiation, transient increase of DNA synthesis, called clonal expansion, and transient hyperphosphorylation of retinoblastoma protein (Rb) are observed. We investigated the role of these phenomena in insulin-induced adipocyte differentiation of 3T3-L1 cells. Insulin-induced clonal expansion, Rb phosphorylation and adipocyte differentiation were all inhibited by the PI 3-kinase inhibitors and rapamycin, but not the MEK inhibitor, whereas the MEK inhibitor, but not PI 3-kinase inhibitors or rapamycin, decreased c-fos induction. We conclude that insulin induces hyperphosphorylation of Rb via PI 3-kinase and mTOR dependent pathway, which promotes clonal expansion and adipocyte differentiation of 3T3-L1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3T3 Cells
  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipocytes / enzymology
  • Adipocytes / metabolism
  • Androstadienes / pharmacology
  • Animals
  • Cell Differentiation* / drug effects
  • Clone Cells / cytology
  • Clone Cells / drug effects
  • Clone Cells / enzymology
  • Clone Cells / metabolism
  • Dexamethasone / pharmacology
  • Flavonoids / pharmacology
  • Insulin / pharmacology
  • Insulin Antagonists / pharmacology
  • MAP Kinase Kinase 1
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation / drug effects
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Kinases*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-fos / antagonists & inhibitors
  • Proto-Oncogene Proteins c-fos / metabolism
  • Retinoblastoma Protein / metabolism*
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases
  • Wortmannin

Substances

  • Androstadienes
  • Flavonoids
  • Insulin
  • Insulin Antagonists
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-fos
  • Retinoblastoma Protein
  • Dexamethasone
  • Protein Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Protein-Serine-Threonine Kinases
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • 1-Methyl-3-isobutylxanthine
  • Sirolimus
  • Wortmannin