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

FEBS Letters

Ingley, Evan¹  Hemmings, Brian A.¹ 

[1] Friedrich Miescher-Institut, Postfach 2543, Basel CH-4002, Switzerland

关键词: Inosine-5′ monophosphate dehydrogenase;    Pleckstrin homology domain;    Protein kinase B;    Akt;    Guanosine-triphosphate;   

DOI  :  10.1016/S0014-5793(00)01866-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown