Mechanism of PI 3-kinase activation during adipocyte differentiation

脂肪细胞的分化是能量平衡和胰岛素敏感性的重要方面。在本研究项目中，我们发现PI 3-激酶在脂肪细胞分化过程中通过与酪氨酸磷酸化IRS-1结合而被激活。我们现在正试图鉴定一种在脂肪细胞分化过程中使IRS-1磷酸化的酪氨酸激酶。我们还发现PI 3-激酶在脂肪细胞特异性蛋白的翻译步骤中促进脂肪形成，并且丝氨酸苏氨酸激酶Akt诱导的4 E-BP 1磷酸化是PI 3-激酶介导的翻译起始中的重要步骤。cAMP的细胞内浓度对于脂肪细胞中的脂肪形成以及胰岛素作用是至关重要的。我们证明磷酸二酯酶（PDE）3B在cAMP的调节中起着重要作用。此外，Akt通过直接磷酸化酶介导PDE 3B的活化。

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.