作者
Ruzica Bago, Nazma Malik, Michael J Munson, Alan R Prescott, Paul Davies, Eeva Sommer, Natalia Shpiro, Richard Ward, Darren Cross, Ian G Ganley, Dario R Alessi
发表日期
2014/11/1
期刊
Biochemical Journal
卷号
463
期号
3
页码范围
413-427
出版商
Portland Press Ltd.
简介
The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM IC50in vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Moreover, we explored whether SGK3 (serum- and glucocorticoid …
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R Bago, N Malik, MJ Munson, AR Prescott, P Davies… - Biochemical Journal, 2014