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XB-ART-34728
Proc Natl Acad Sci U S A October 31, 2006; 103 (44): 16313-8.

Jun NH2-terminal kinase (JNK) prevents nuclear beta-catenin accumulation and regulates axis formation in Xenopus embryos.

Liao G , Tao Q , Kofron M , Chen JS , Schloemer A , Davis RJ , Hsieh JC , Wylie C , Heasman J , Kuan CY .


Abstract
Jun NH(2)-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 Wnt 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.

PubMed ID: 17060633
PMC ID: PMC1637579
Article link: Proc Natl Acad Sci U S A
Grant support: [+]
Genes referenced: camk2g cdk1 cdk20 ctnnb1 dvl2 gsc gsk3a gsk3b hsp70 jun map2k7 mapk8 nfatc2 nodal3.1 nodal3.2 sia1 tcf3 tuba4b wnt11 wnt3a wnt5a
Morpholinos: mapk8 MO1


Article Images: [+] show captions
References [+] :
Bagowski, c-Jun N-terminal kinase activation in Xenopus laevis eggs and embryos. A possible non-genomic role for the JNK signaling pathway. 2001, Pubmed, Xenbase


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