Dev Biol 2016 Aug 01;4161:42-51. doi: 10.1016/j.ydbio.2016.06.014.

JNK does not regulate meiotic progression in Xenopus oocytes: The strange case of pJNK and pERK.

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Xenopus ERK2, also known as Xp42 MAPK, is activated by progesterone and regulates meiotic progression in the oocytes through activation of the phosphatase Cdc25C and inhibition of the protein kinase Myt1, thus promoting dephosphorylation and activation of cyclinB/Cdc2 (MPF). Indeed, it has been reported that stress protein kinases p38 and JNK are activated during meiotic progression and, more specifically, that p38γ regulates meiosis through activation of Cdc25C. However, the role of JNK in meiotic progression is not so clear, and despite a 42kDa protein is detected with pJNK antibodies (XpJNK-p42), the specific isoform activated by progesterone has not been characterized in detail. The serine/threonine kinase MEKK1, an upstream activator of JNK and p38, is activated during stress conditions and regulates apoptosis in different cell types. Here we show that ectopic expression of a constitutively active MEKK1 in Xenopus oocytes induces phosphorylation of p38, JNK and ERK and accelerates meiotic progression induced by progesterone. Inhibition of each individual pathway reduces the acceleration of meiosis induced by MEKK1. However, constitutively active MEKK1 induces phosphorylation of two JNK isoforms (p40 and p49, corresponding to JNK1-1 and JNK1-2 respectively) distinct to the p42 protein detected with pJNK antibodies during meiotic progression (XpJNK-p42). Moreover, a constitutively active MKK7, which specifically activates the JNK signaling pathway and induces phosphorylation of the p40 and p49 isoforms, does not accelerate meiotic progression. Immunoprecipitation of the p42 protein with pJNK antibodies and subsequent analysis by mass spectrometry shows that XpJNK-p42 is, in fact, pERK2. Ectopic expression of ERK2 in oocytes treated with progesterone or hyperosmotic shock indicates that ERK2 is phosphorylated in both conditions but is only detected with pJNK antibodies in progesterone-treated oocytes. In addition, mature oocytes only present a moderate increase of Jun kinase activity, which is not inhibited by SP600125. In conclusion, JNKs are not activated during meiotic progression and XpJNK-p42 is a post-translational modification of pERK induced by progesterone.

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Species referenced: Xenopus
Genes referenced: cdc25c cdk20 grap2 il12b jun map2k7 map3k1 mapk1 mapk14 mapk8 myt1 prim1 rpsa