Retinoblastoma protein phosphorylation via PI 3-kinase and mTOR pathway regulates adipocyte differentiation.
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.
Usui
I
I
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194, Japan.
Haruta
T
T
Iwata
M
M
Takano
A
A
Uno
T
T
Kawahara
J
J
Ueno
E
E
Sasaoka
T
T
Kobayashi
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin
D015056:1-Methyl-3-isobutylxanthine; D000730:Androstadienes; D003907:Dexamethasone; D005419:Flavonoids; D007328:Insulin; D007329:Insulin Antagonists; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016760:Proto-Oncogene Proteins c-fos; D016160:Retinoblastoma Protein; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin; C546843:mTOR protein, mouse; C482127:Map2k1 protein, mouse; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one