TY - JOUR
T1 - Xp38gamma/SAPK3 promotes meiotic G(2)/M transition in Xenopus oocytes and activates Cdc25C.
AU - Perdiguero, Eusebio
AU - Pillaire, Marie-Jeanne
AU - Bodart, Jean-Francois
AU - Hennersdorf, Florian
AU - Frödin, Morten
AU - Duesbery, Nicholas S
AU - Alonso, Gema
AU - Nebreda, Angel R
N1 - Keywords: Animals; Cell Cycle Proteins; Cyclic AMP-Dependent Protein Kinases; Enzyme Activation; Female; G2 Phase; Gene Expression; Meiosis; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 12; Mitogen-Activated Protein Kinases; Mitosis; Oocytes; Oogenesis; Phosphorylation; Progesterone; Ribosomal Protein S6 Kinases, 90-kDa; Xenopus; Xenopus Proteins; cdc25 Phosphatases
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
U2 - 10.1093/emboj/cdg559
DO - 10.1093/emboj/cdg559
M3 - Journal article
C2 - 14592973
SN - 0261-4189
VL - 22
SP - 5746
EP - 5756
JO - EMBO Journal
JF - EMBO Journal
IS - 21
ER -