定量蛋白质组学揭示了胰腺β细胞中PP2A催化亚基的新型蛋白质相互作用伙伴。
Quantitative proteomics reveals novel protein interaction partners of PP2A catalytic subunit in pancreatic β-cells.
作者信息
Zhang Xiangmin, Damacharla Divyasri, Ma Danjun, Qi Yue, Tagett Rebecca, Draghici Sorin, Kowluru Anjaneyulu, Yi Zhengping
机构信息
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, 48201, USA.
Department of Computer Science, College of Engineering, Wayne State University, Detroit, MI, USA.
出版信息
Mol Cell Endocrinol. 2016 Mar 15;424:1-11. doi: 10.1016/j.mce.2016.01.008. Epub 2016 Jan 9.
Protein phosphatase 2A (PP2A) is one of the major serine/threonine phosphatases. We hypothesize that PP2A regulates signaling cascades in pancreatic β-cells in the context of glucose-stimulated insulin secretion (GSIS). Using co-immunoprecipitation (co-IP) and tandem mass spectrometry, we globally identified the protein interaction partners of the PP2A catalytic subunit (PP2Ac) in insulin-secreting pancreatic β-cells. Among the 514 identified PP2Ac interaction partners, 476 were novel. This represents the first global view of PP2Ac protein-protein interactions caused by hyperglycemic conditions. Additionally, numerous PP2Ac partners were found involved in a variety of signaling pathways in the β-cell function, such as insulin secretion. Our data suggest that PP2A interacts with various signaling proteins necessary for physiological insulin secretion as well as signaling proteins known to regulate cell dysfunction and apoptosis in the pancreatic β-cells.
蛋白磷酸酶2A（PP2A）是主要的丝氨酸/苏氨酸磷酸酶之一。我们推测，在葡萄糖刺激的胰岛素分泌（GSIS）过程中，PP2A调节胰腺β细胞中的信号级联反应。我们使用免疫共沉淀（co-IP）和串联质谱法，全面鉴定了胰岛素分泌胰腺β细胞中PP2A催化亚基（PP2Ac）的蛋白质相互作用伙伴。在鉴定出的514个PP2Ac相互作用伙伴中，有476个是新发现的。这代表了高血糖条件下PP2Ac蛋白质-蛋白质相互作用的首个全局视图。此外，发现许多PP2Ac伙伴参与β细胞功能中的多种信号通路，如胰岛素分泌。我们的数据表明，PP2A与生理胰岛素分泌所需的各种信号蛋白以及已知调节胰腺β细胞功能障碍和凋亡的信号蛋白相互作用。
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