National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Protein Cell. 2013 Jul;4(7):520-8. doi: 10.1007/s13238-013-3005-1. Epub 2013 Jun 6.
The peptide angiotensin IV (Ang IV) is a derivative of angiotensin II. While insulin regulated amino peptidase (IRAP) has been proposed as a potential receptor for Ang IV, the signalling pathways of Ang IV through IRAP remain elusive. We applied high-resolution mass spectrometry to perform a systemic quantitative phosphoproteome of Neura-2A (N2A) cells treated with and without Ang IV using sta ble-isotope labeling by amino acids in cell culture (SILAC), and identified a reduction in the phosphorylation of a major Ser/Thr protein phosphorylase 1 (PP1) upon Ang IV treatment. In addition, spinophilin (spn), a PP1 regulatory protein that plays important functions in the neural system, was expressed at higher levels. Immunoblotting revealed decreased phosphorylation of p70S6 kinase (p70(S6K)) and the major cell cycle modulator retinoblastoma protein (pRB). These changes are consistent with an observed decrease in cell proliferation. Taken together, our study suggests that Ang IV functions via regulating the activity of PP1.
肽血管紧张素 IV（Ang IV）是血管紧张素 II 的衍生物。虽然胰岛素调节氨肽酶（IRAP）已被提议为 Ang IV 的潜在受体，但 Ang IV 通过 IRAP 的信号通路仍然难以捉摸。我们应用高分辨率质谱法，使用细胞培养中的稳定同位素标记的氨基酸（SILAC），对用和不用 Ang IV 处理的 Neura-2A（N2A）细胞进行系统的定量磷酸化蛋白质组学分析，发现 Ang IV 处理后主要的丝氨酸/苏氨酸蛋白磷酸酶 1（PP1）的磷酸化减少。此外，在神经系统中发挥重要功能的 PP1 调节蛋白 spinophilin（spn）的表达水平更高。免疫印迹显示 p70S6 激酶（p70(S6K)) 和主要的细胞周期调节剂视网膜母细胞瘤蛋白（pRB）的磷酸化减少。这些变化与观察到的细胞增殖减少一致。综上所述，我们的研究表明，Ang IV 通过调节 PP1 的活性发挥作用。
