Mechanism of PI 3-kinase activation during adipocyte differentiation

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Differentiation of adipocytes is an important aspect of energy homeostasis as well as insulin sensitivity. In this research project, we have found that PI 3-kinase is activated during adpocyte differentiation by associating with tyrosine-phosphorylated IRS-1. We have now trying to identify a tyrosine kinase that phosphorylates IRS-1 during adpipocyte differentiation. We also found that PI 3-kinase promotes adipogenesis at the step of translation of adipocyte-specific proteins and that phosphorylation of 4E-BP1 induced by a serine threonin kinase Akt is an important step in PI 3-kinase-mediated translational initiation. Intracellular concentration of cAMP is critical for adipogenesis as well as insulin action in adipocytes. We demonstrated that phosphodiesterase (PDE) 3B plays a major role in regulation of cAMP. Furthermore, Akt mediates activation of PDE 3B by directly phosphorylating the enzyme.