PKB/Akt interacts with inosine‐5′ monophosphate dehydrogenase through its pleckstrin homology domain
- 31 July 2000
- journal article
- Published by Wiley in FEBS Letters
- Vol. 478 (3) , 253-259
- https://doi.org/10.1016/s0014-5793(00)01866-4
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.Keywords
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