A comparison of demethoxyviridin and wortmannin as inhibitors of phosphatidylinositol 3-kinase.

Abstract:

: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 (p85 alpha) 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 cerevisiae (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 Schizosaccharomyces pombe.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Woscholski R,Kodaki T,McKinnon M,Waterfield MD,Parker PJ

doi

10.1016/0014-5793(94)80482-6

subject

Has Abstract

pub_date

1994-04-04 00:00:00

pages

109-14

issue

2

eissn

0014-5793

issn

1873-3468

pii

0014-5793(94)80482-6

journal_volume

342

pub_type

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