PKB/Akt interacts with inosine-5′ monophosphate dehydrogenase through its pleckstrin homology domain
Ingley, E.ORCID: 0000-0002-8112-9134 and Hemmings, B.A.
(2000)
PKB/Akt interacts with inosine-5′ monophosphate dehydrogenase through its pleckstrin homology domain.
FEBS Letters, 478
(3).
pp. 253-259.
*No subscription required
Abstract
The pleckstrin homology (PH) domain of the protooncogenic serine/threonine protein kinase PKB/Akt can bind phosphoinositides. A yeast- based two-hybrid system was employed which identified inosine-5' monophosphate dehydrogenase (IMPDH) type II as specifically interacting with PKB/Akts PH domain. IMPDH catalyzes the rate-limiting step of de novo guanosine-triphosphate (GTP) biosynthesis. Using purified fusion proteins, PKB/Akts PH domain and IMPDH associated in vitro and this association moderately activated IMPDH. Purified PKB/Akt also associated with IMPDH in vitro. We could specifically pull-down PKB/Akt or IMPDH from mammalian cell lysates using glutathione-S-transferase (GST)-IMPDH or GST-PH domain fusion proteins, respectively. Additionally, PKB/Akt and IMPDH could be co- immunoprecipitated from COS cell lysates and active PKB/Akt could phosphorylate IMPDH in vitro. These results implicate PKB/Akt in the regulation of GTP biosynthesis through its interaction with IMPDH, which is involved in providing the GTP pool used by signal transducing G-proteins.
Item Type: | Journal Article |
---|---|
Publisher: | Wiley |
Copyright: | © 2000 Federation of European Biochemical Societies. |
URI: | http://researchrepository.murdoch.edu.au/id/eprint/39576 |
![]() |
Item Control Page |