Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation

cGMP‐inhibited cAMP phosphodiesterase 3A (PDE3A) is expressed in mouse oocytes, and its function is indispensable for meiotic maturation as demonstrated by genetic ablation. Moreover, PDE3 activity is required for insulin/insulin‐like growth factor‐1 stimulation of Xenopus oocyte meiotic resumption....

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Veröffentlicht in:The EMBO journal 2006-12, Vol.25 (24), p.5716-5725
Hauptverfasser: Han, Seung Jin, Vaccari, Sergio, Nedachi, Taku, Andersen, Carsten B, Kovacina, Kristina S, Roth, Richard A, Conti, Marco
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Sprache:eng
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Zusammenfassung:cGMP‐inhibited cAMP phosphodiesterase 3A (PDE3A) is expressed in mouse oocytes, and its function is indispensable for meiotic maturation as demonstrated by genetic ablation. Moreover, PDE3 activity is required for insulin/insulin‐like growth factor‐1 stimulation of Xenopus oocyte meiotic resumption. Here, we investigated the cAMP‐dependent protein kinase B (PKB)/Akt regulation of PDE3A and its impact on oocyte maturation. Cell‐free incubation of recombinant mouse PDE3A with PKB/Akt or cAMP‐dependent protein kinase A catalytic subunits leads to phosphorylation of the PDE3A protein. Coexpression of PDE3A with constitutively activated PKB/Akt (Myr‐Akt) increases PDE activity as well as its phosphorylation state. Injection of pde3a mRNA potentiates insulin‐dependent maturation of Xenopus oocytes and rescues the phenotype of pde3 −/− mouse oocytes. This effect is greatly decreased by mutation of any of the PDE3A serines 290–292 to alanine in both Xenopus and mouse. Microinjection of myr‐Akt in mouse oocytes causes in vitro meiotic maturation and this effect requires PDE3A. Collectively, these data indicate that activation of PDE3A by PKB/Akt‐mediated phosphorylation plays a role in the control of PDE3A activity in mammalian oocytes.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601431