Jun NH2-terminal kinase (JNK) prevents nuclear β-catenin accumulation and regulates axis formation in Xenopus embryos
Jun NH2-terminal kinase (JNK) prevents nuclear β-catenin accumulation and regulates axis formation in Xenopus embryos
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DOI：
10.1073/pnas.0602557103
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发表时间：
2006-10-31
影响因子：
11.1
通讯作者：
Kuan, Chia-Yi
中科院分区：
文献类型：
--
作者：
Liao, Guanghong;Tao, Qinghua;Kuan, Chia-Yi
nh2末端激酶（JNKs）通过非规范的Wnt/平面细胞极性通路调节非洲爪蟾胚胎的趋同伸展运动。此外，从卵母细胞成熟到未定义功能的原肠胚形成，母体JNK的活性水平很高。在这里，我们发现母体JNK的激活需要dishevelded， JNK在爪蟾胚胎的细胞核中富集。尽管糖原合成酶激酶-3介导的β -连环蛋白降解不需要JNK活性，但通过morpholino-反义寡核苷酸抑制母体JNK信号会导致爪蟾胚胎过度活化和Wnt/ β -连环蛋白靶基因的异位表达。这些影响与细胞核和非膜结合β -连环蛋白水平的增加有关。此外，腹侧注射构成型活性Jnk mRNA可阻断β -catenin诱导的轴复制，背侧注射活性Jnk mRNA可降低爪蟾胚胎背侧标记基因的表达。在哺乳动物细胞中，JNK信号的激活降低了wnt3a诱导的和β -连环蛋白介导的基因表达。此外，JNK信号的激活可迅速诱导β -连环蛋白的核输出。综上所述，这些结果表明JNK通过调节β -连环蛋白的核质转运而不是其细胞质稳定性来拮抗典型的Writ途径。因此，早期爪蟾胚胎中母体JNK的高水平持续活性可能为控制背轴形成提供了一种定时机制。
Jun NH2-terminal kinases (JNKs) regulate convergent extension movements in Xenopus embryos through the noncanonical Wnt/planar cell polarity pathway. In addition, there is a high level of maternal JNK activity spanning from oocyte maturation until the onset of gastrulation that has no defined functions. Here, we show that maternal JNK activation requires Dishevelled and JNK is enriched in the nucleus of Xenopus embryos. Although JNK activity is not required for the glycogen synthase kinase-3-mediated degradation of beta-catenin, inhibition of the maternal JNK signaling by morpholino-antisense oligos causes hyperdorsalization of Xenopus embryos and ectopic expression of the Wnt/beta-catenin target genes. These effects are associated with an increased level of nuclear and nonmembrane-bound beta-catenin. Moreover, ventral injection of the constitutive-active Jnk mRNA blocks beta-catenin-induced axis duplication, and dorsal injection of active Jnk mRNA into Xenopus embryos decreases the dorsal marker gene expression. In mammalian cells, activation of JNK signaling reduces Wnt3A-induced and beta-catenin-mediated gene expression. Furthermore, activation of JNK signaling rapidly induces the nuclear export of beta-catenin. Taken together, these results suggest that JNK antagonizes the canonical Writ pathway by regulating the nucleocytoplasmic transport of beta-catenin rather than its cytoplasmic stability. Thus, the high level of sustained maternal JNK activity in early Xenopus embryos may provide a timing mechanism for controlling the dorsal axis formation.