肾脏多巴胺D1受体在机体血压调控中具有重要作用，但高血压状态下D1受体过度磷酸化导致其功能受损。G蛋白激酶4（GRK4）和蛋白磷酸酶2A（PP2A）分别使D1受体磷酸化和去磷酸化。目前研究显示仅抑制GRK4并不能使D1受体磷酸化水平回复正常，同时发现高血压状态下PP2A活性增高，提示PP2A调控D1受体去磷酸化的功能出现异常，其原因不明。我们前期工作发现过度磷酸化的D1受体与PP2A相互作用减弱，其自身SUMO-1修饰增强。因此，我们设想高血压状态下D1受体的过度磷酸化诱导了SUMO-1对其特定部位的SUMO化修饰，由此影响了PP2A同磷酸化的D1受体相互作用，导致D1受体去磷酸化受阻、功能障碍。本研究拟在细胞和整体动物水平，观察D1受体磷酸化与其SUMO化的调控关系，并探讨D1受体SUMO化对PP2A与D1受体相互作用的影响，以期为高血压的防治提供新思路。

The renal dopamine D1 receptor plays a crucial role in blood pressure regulation. However, there exists a defect in D1 receptor function in spontaneously hypertension that is associated with hyperphosphorylation of the D1 receptor. G protein-coupled receptor kinase 4 (GRK4) and protein phosphatase 2A (PP2A) are critical in the regulation of phosphorylation and dephosphorylation of the renal D1 receptor, respectively. Studies have shown that PP2A activity and protein levels were increased in renal cortical tubules in hypertension, which does not cause D1 receptor dephosphorylation efficiently. In addition, selective renal reduction of GRK4 expression and activity does not make level of D1 receptor phosphorylation returned to normal. The exact underlying mechanism is not clear.Our preliminary study discovered that hyperphosphorylated D1 receptor was shown to attenuate its interaction with PP2A and promote its SUMO-1 modification. SUMO-1 is the small unbiquitin-like modify poly-peptide which can affect protein-protein interaction. Therefore, we hypothesized that D1 receptor phosphorylation promotes SUMO-1 modification of D1 receptor, thus interfering its interaction with PP2A, which led to impaired dephosphorylation and function of D1 receptor. Through cellular and animal experiments, we will clarify an interplay between phosphorylation and sumoylation of D1 receptor, and interaction of D1 receptor and PP2A resulted in sumoylation of dopamine D1 receptor. The results of the project will be beneficial to development of new understandings for prevention and treatment of hypertension.