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  • The EMBO Journal (2003) 22, 5746 - 5756
  • doi:10.1093/emboj/cdg559

Xp38big gamma/SAPK3 promotes meiotic G2/M transition in Xenopus oocytes and activates Cdc25C

Eusebio Perdiguero1, Marie-Jeanne Pillaire2, Jean-Francois Bodart3, Florian Hennersdorf1, Morten Frödin4, Nicholas S. Duesbery5, Gema Alonso1 and Angel R. Nebreda1

  1. European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
  2. Present address: Institut de Pharmacologie et de Biologie structurale, Toulouse, France
  3. Universite des Sciences et Technologies de Lille, Villeneuve, France
  4. Glostrup Hospital, Glostrup, Denmark
  5. Van Andel Research Institute, Grand Rapids, MI, USA

Correspondence to:

Angel R. Nebreda, E-mail: nebreda@EMBL.de

Received 28 March 2003; Accepted 11 September 2003; Revised 7 August 2003

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 G2/M progression of Xenopus oocytes.

  • Keywords:

    • Cdc25,
    • meiotic maturation,
    • p38,
    • SAPK3,
    • Xenopus oocyte