Xp38gamma/SAPK3 promotes meiotic G(2)/M transition in Xenopus oocytes and activates Cdc25C.
We have studied the role of p38 mitogen-activated protein kinases (MAPKs) in the meiotic maturation of Xenopus oocytes. Overexpression of a constitutively active mutant of the p38 activator MKK6 accelerates progesterone-induced maturation. Immunoprecipit ation experiments indicate that p38gamma/SAPK3 is the major p38 activated by MKK6 in the oocytes. We have cloned Xenopus p38gamma (Xp38gamma) and show that co-expression of active MKK6 with Xp38gamma induces oocyte maturation in the absence of progesterone. The maturation induced by Xp38gamma requires neither protein synthesis nor activation of the p42 MAPK-p90Rsk pathway, but it is blocked by cAMP-dependent protein kinase. A role for the endogenous Xp38gamma in progesterone-induced maturation is supported by the inhibitory effect of kinase-dead mutants of MKK6 and Xp38gamma. Furthermore, MKK6 can rescue the inhibition of oocyte maturation by anthrax lethal factor, a protease that inactivates MAPK kinases. We also show that Xp38gamma can activate the phosphatase XCdc25C, and we identified Ser205 of XCdc25C as a major phosphorylation site for Xp38gamma. Our results indicate that phosphorylation of XCdc25C by Xp38gamma/SAPK3 is important for the meiotic G(2)/M progression of Xenopus oocytes.
Perdiguero
Eusebio
E
European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Pillaire
Marie-Jeanne
MJ
Bodart
Jean-Francois
JF
Hennersdorf
Florian
F
Frödin
Morten
M
Duesbery
Nicholas S
NS
Alonso
Gema
G
Nebreda
Angel R
AR
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D016195:G2 Phase; D015870:Gene Expression; D066298:In Vitro Techniques; D008540:Meiosis / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048291:Mitogen-Activated Protein Kinase 12; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009866:Oogenesis / Q000502:physiology; D010766:Phosphorylation; D011374:Progesterone / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism*
D018797:Cell Cycle Proteins; D029867:Xenopus Proteins; D011374:Progesterone; D048291:Mitogen-Activated Protein Kinase 12; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; C448499:p42 MAP kinase, Xenopus; D020687:cdc25 Phosphatases