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 r etinoblastoma protein (Rb) are observed. We investigated the role of these phenomena in insulin-induced adipocyte differentiation of 3T3-L1 cells. Ins ulin-induced clonal expansion, Rb phosphorylation and adipocyte differentia tion were all inhibited by the PI 3 kinase inhibitors and rapamycin, but no t the MEK inhibitor, whereas the MEK inhibitor, but not PI 3-kinase inhibit ors or rapamycin, decreased c-fos induction. We conclude that insulin induc es hyperphosphorylation of Rb via PI 3-kinase and mTOR dependent pathway, w hich promotes clonal expansion and adipocyte differentiation of 3T3-L1 cell s. (C) 2000 Academic Press.