Brefeldin A provokes indirect activation of cdc2 kinase (MPF) in Xenopus oocytes, resulting in meiotic cell division.
Brefeldin A, a fungal metabolite which disrupts protein traffic, provokes indirect activation of cdc2 protein kinase in Xenopus oocytes. Cdc2 protein kinase activation was judged by MPF (M-phase factor) transfer activity, histone H1 kinase activity, and phosphorylation in vivo of the guanine-nucleotide exchange complex EF-1 beta gamma delta. Oocytes resumed complete meiosis upon brefeldin A treatment. Cdc2 protein kinase, MAP kinase, cyclin B, MPF, and protein synthesis changes were all comparable in brefeldin A-treated oocytes and in progesterone-induced oocytes. ED50 for brefeldin A was 0.6 microM. Brefeldin A activation of cdc2 protein kinase occurs with a long time course. Simultaneous treatment of the oocytes at a subthreshold concentration of 1 nM progesterone and 30 microM brefeldin A considerably shortened the kinetics of maturation. Brefeldin A induction of maturation was sensitive to drugs that act on cAMP metabolism. ID50 for IBMX was 0.1 mM, compared to 1 mM for progesterone-treated oocytes. Brefeldin A inhibited protein traffic in oocytes as determined from protein export experiments. ID50 was between 0.1 and 1 microM. Our results give new insights into the possible mechanism of induction of meiotic maturation and further demonstrate that brefeldin A acts on cell cycle regulatory elements.
Mulner-Lorillon
O
O
Biologie Cellulaire de l'ovocyte, CNRS URA 1449, Université Pierre et Marie Curie, Paris, France.
Bellé
R
R
Cormier
P
P
Drewing
S
S
Minella
O
O
Poulhe
R
R
Schmalzing
G
G
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D020126:Brefeldin A; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D016200:Maturation-Promoting Factor / Q000378:metabolism*; D008540:Meiosis / Q000187:drug effects*; D009865:Oocytes / Q000187:drug effects* / Q000201:enzymology; D009866:Oogenesis / Q000187:drug effects; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology; D006656:Protamine Kinase / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014982:Xenopus laevis
D003517:Cyclopentanes; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D005576:Colforsin; D020126:Brefeldin A; D011374:Progesterone; D002772:Cholera Toxin; D003513:Cycloheximide; D000242:Cyclic AMP; D006656:Protamine Kinase; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; C047983:1,9-dideoxyforskolin; D015056:1-Methyl-3-isobutylxanthine