Xp38 /SAPK3 promotes meiotic G2/M transition in Xenopus oocytes and activates Cdc25C

• Published in: The EMBO journal 2003-11, Vol.22 (21), p.5746-5756
• Main Author: Perdiguero, E.
• Format: Article
• Language: English
• Subjects: Protein synthesis
• ISSN: 1460-2075; 0261-4189; 1460-2075
• DOI: 10.1093/emboj/cdg559

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 p38[gamma]/SAPK3 is the major p38 activated by MKK6 in the oocytes. We have cloned Xenopus p38[gamma] (Xp38[gamma]) and show that co-expression of active MKK6 with Xp38[gamma] induces oocyte maturation in the absence of progesterone. The maturation induced by Xp38[gamma] 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 Xp38[gamma] in progesterone-induced maturation is supported by the inhibitory effect of kinase-dead mutants of MKK6 and Xp38[gamma]. Furthermore, MKK6 can rescue the inhibition of oocyte maturation by anthrax lethal factor, a protease that inactivates MAPK kinases. We also show that Xp38[gamma] can activate the phosphatase XCdc25C, and we identified Ser205 of XCdc25C as a major phosphorylation site for Xp38[gamma]. Our results indicate that phosphorylation of XCdc25C by Xp38[gamma]/SAPK3 is important for the meiotic G2/M progression of Xenopus oocytes.