A comparison of demethoxyviridin and wortmannin as inhibitors of phosphatidylinositol 3‐kinase

FEBS Letters

Waterfield, Michael D.¹  McKinnon, Murray²  Parker, Peter J.²  Kodaki, Tsutomu²  Woscholski, Ruediger² 

[1] Ludwig Institute for Cancer Research, 91 Riding House Street, London, W1P 8BT, UK;Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK

关键词: Demethoxyviridin;    Wortmannin;    Lipid kinase;    Phosphatidylinositol 3-kinase;    DMV: demethoxyviridin;    Ptdlns: phosphatidylinositol;    MLCK: myosin light chain kinase;   

DOI  :  10.1016/0014-5793(94)80482-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The mammalian Ptdlns 3-kinase is shown to be inhibited by low nanomolar concentrations of demethoxyviridin, an antifungal agent structurally related to wortmannin. The inhibitory potency of both compounds could be observed in purified Ptdlns 3-kinase whether or not the regulatory subunit (p85α) was present, suggesting that the inhibitors bind to the catalytic subunit (p110) of the Ptdlns 3-kinase. These inhibitors also show similar potency against the intrinsic p85-phosphorylating activity of the p110-kinase. However, the structurally related Ptdlns 3-kinase from Saccharomyces cerevisae (Vps34p) is not inhibited by either compound. Both inhibitors target the mammalian Ptdlns 3-kinase in vitro and in vivo, implying that these compounds should be useful in suppressing Ptdlns 3-kinase in mammalian systems. The inhibitors did not affect the mammalian Ptdlns 4-kinase, but they are able to inhibit a membrane-associated Ptdlns 4-kinase from Schizosacchromyces pombe.

【 授权许可】

Unknown