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A comparison of demethoxyviridin and wortmannin as inhibitors of phosphatidylinositol 3‐kinase
Author(s) -
Woscholski Ruediger,
Kodaki Tsutomu,
McKin Murray,
Waterfield Michael D.,
Parker Peter J.
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)80482-6
Subject(s) - wortmannin , biochemistry , kinase , phosphatidylinositol , biology , cyclin dependent kinase 7 , protein kinase a , mitogen activated protein kinase kinase
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 .