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PKB/Akt interacts with inosine-5′ monophosphate dehydrogenase through its pleckstrin homology domain
Journal article   Peer reviewed

PKB/Akt interacts with inosine-5′ monophosphate dehydrogenase through its pleckstrin homology domain

E. Ingley and B.A. Hemmings
FEBS Letters, Vol.478(3), pp.253-259
2000
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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.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.25 Molecular & Cell Biology - Cancer, Autophagy & Apoptosis
1.25.803 PI3K/AKT/mTOR Pathway
Web Of Science research areas
Biochemistry & Molecular Biology
Biophysics
Cell Biology
ESI research areas
Biology & Biochemistry
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