Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt

被引:58
作者
Li, Xin [1 ]
Yang, Haihua [2 ]
Liu, Jianyu [1 ]
Schmidt, Micheal D. [4 ]
Gao, Tianyan [1 ,3 ]
机构
[1] Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA
[2] Taizhou Hosp, Dept Oncol, Taizhou 317000, Zhejian, Peoples R China
[3] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA
[4] Univ Kentucky, Dept Biol, Lexington, KY 40536 USA
基金
美国国家卫生研究院;
关键词
PHLPP; Scribble; Akt phosphorylation; scaffolding protein; PROTEIN-KINASE-C; TUMOR SUPPRESSORS; CELL POLARITY; LOCALIZATION; PHOSPHATASE; EXPRESSION; MECHANISM; GROWTH;
D O I
10.1038/embor.2011.106
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PHLPP1 (PH domain leucine-rich-repeats protein phosphatase) is a Ser/Thr protein phosphatase that acts as a tumour suppressor by negatively regulating Akt. Here, we show that PHLPP1 is recruited to the cell membrane by binding to a scaffolding protein: Scribble. Knockdown of Scribble (Scrib) results in redistribution of PHLPP1 from the membrane to the cytoplasm and an increase in Akt phosphorylation, whereas overexpression of Scrib has the opposite effect. Furthermore, PHLPP1-dependent inhibition of cell proliferation is facilitated by the formation of a Scrib, PHLPP1 and Akt trimeric complex. Thus, our findings identify a functional interaction between PHLPP1 and Scrib in negatively regulating Akt signalling.
引用
收藏
页码:818 / 824
页数:7
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