Inhibition of Xenopus oocyte meiotic maturation by catalytically inactive protein kinase A.
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, XPKAalpha and XPKAbeta. 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.
Schmitt
Anja
A
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Nebreda
Angel R
AR
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000502:physiology*; D005260:Female; D008540:Meiosis / Q000187:drug effects; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology; D021122:Protein Subunits; D019893:Ribosomal Protein S6 Kinases / Q000502:physiology; D014981:Xenopus; D020687:cdc25 Phosphatases / Q000502:physiology
D018797:Cell Cycle Proteins; D021122:Protein Subunits; D011374:Progesterone; D019893:Ribosomal Protein S6 Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020687:cdc25 Phosphatases