Inhibition of Xenopus oocyte meiotic maturation by catalytically inactive protein kinase A
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Communicated by Joan V. Ruderman, Harvard Medical School, Boston, MA (received for review October 25, 2001)
Abstract
Progesterone induces G2-arrested Xenopus oocytes to develop into fertilizable eggs in a process called meiotic maturation. Protein kinase A (PKA), the cAMP-dependent protein kinase, has long been known to be a potent inhibitor of meiotic maturation, but little information is available on how PKA functions. We have cloned two Xenopus PKA catalytic subunit isoforms, XPKAα and XPKAβ. These proteins are 89% identical and both inhibit progesterone-induced meiotic maturation when overexpressed at low levels, suggesting that PKA activity is tightly regulated in the oocyte. Unexpectedly, catalytically inactive XPKA mutants are able to block progesterone-induced maturation as efficiently as the wild-type active XPKA. These mutants also block meiotic maturation induced by Mos, but are less efficient at inhibiting Cdc25C-induced maturation. Our results indicate that PKA can inhibit meiotic maturation by a novel mechanism, which does not require its kinase activity and is also independent of binding to the PKA regulatory subunits.
Footnotes
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↵ * To whom reprint requests should be addressed. E-mail: nebreda{at}EMBL-heidelberg.de.
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Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AJ413218 and AJ413219).
- Abbreviations:
- GST,
- glutathione S-transferase;
- GVBD,
- germinal vesicle breakdown;
- H1K,
- histone H1 kinase;
- MAPK,
- mitogen-activated protein kinase;
- PDK1,
- 3-phosphoinositide-dependent kinase-1;
- PKA,
- protein kinase A;
- PKAc,
- PKA catalytic subunit;
- PKA-R,
- PKA regulatory subunit;
- PKI,
- PKA inhibitor
- Copyright © 2002, The National Academy of Sciences
