The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.
Tóm tắt
The serine/threonine kinase Xgsk-3 and the intracellular protein beta-catenin are necessary for the establishment of the dorsal-ventral axis in Xenopus. Although genetic evidence from Drosophila indicates that Xgsk-3 is upstream of beta-catenin, direct interactions between these proteins have not been demonstrated. We demonstrate that phosphorylation of beta-catenin in vivo requires an in vitro amino-terminal Xgsk-3 phosphorylation site, which is conserved in the Drosophila protein armadillo. beta-catenin mutants lacking this site are more active in inducing an ectopic axis in Xenopus embryos and are more stable than wild-type beta-catenin in the presence of Xgsk-3 activity, supporting the hypothesis that Xgsk-3 is a negative regulator of beta-catenin that acts through the amino-terminal site. Inhibition of endogenous Xgsk-3 function with a dominant-negative mutant leads to an increase in the steady-state levels of ectopic beta-catenin, indicating that Xgsk-3 functions to destabilize beta-catenin and thus decrease the amount of beta-catenin available for signaling. The levels of endogenous beta-catenin in the nucleus increases in the presence of the dominant-negative Xgsk-3 mutant, suggesting that a role of Xgsk-3 is to regulate the steady-state levels of beta-catenin within specific subcellular compartments. These studies provide a basis for understanding the interaction between Xgsk-3 and beta-catenin in the establishment of the dorsal-ventral axis in early Xenopus embryos.
Từ khóa
Tài liệu tham khảo
1990, An early embryonic product of the gene shaggy encodes a serine/threonine protein kinase related to the CDC28/cdc2 + subfamily., EMBO J., 9, 2877, 10.1002/j.1460-2075.1990.tb07477.x
1995, Xwnt8b: A maternally expressed Xenopus Wnt gene with a potential role in establishing the dorso-ventral axis., Development, 121, 2177, 10.1242/dev.121.7.2177
1994, β-catenin localization during Xenopus embryogenesis: Accumulation at tissue and somite boundaries., Development, 120, 3667, 10.1242/dev.120.12.3667
1989, Cortical rotation of the Xenopus egg: Consequences for the anteroposterior pattern of embryonic dorsal development., Development, 107, 37, 10.1242/dev.107.Supplement.37
Heasman, J., Crawford, A. Goldstone, K. Garner-Hamrick, P. Gumbiner, B. McCrea, P. Kintner, C. Noro, C.Y. and Wylie. C. 1994. Overexpression of cadherins and underexpression of β-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. Cell 79: 791–803.
1995, Zebrafish wnt8 and wnt8b share a common activity but are involved in distinct developmental pathways., Development, 121, 1787, 10.1242/dev.121.6.1787
1993, Xwnt-11: A maternally expressed Xenopus Wnt gene., Development, 119, 1161, 10.1242/dev.119.4.1161
1989, Microinjection and expression of synthetic mRNAs in Xenopus embryos., Technique, 1, 76
1993, Xwnt 5A: A maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis., Development, 119, 97, 10.1242/dev.119.1.97
Moon, R.T., Christian, J.L. Campbell, R.M. McGrew, L.L. DeMarais, A.A. Torres, M. Lai, C.-J. Olson, D. and Kelly. G.M. 1993b. Dissecting Wnt signalling pathways and Wnt-sensitive developmental processes through transient misexpression anlyses in embryos of Xenopus laevis. Development (Suppl): 85–94.
1993, Glycogen synthase kinase 3 phospho-rylates Jun family members in vitro and negatively regulates their transactivating potential in cells., Oncogene, 8, 833
1991, The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation., Development, 111, 1029, 10.1242/dev.111.4.1029
1994, Wingless signal and zeste-white 3 kinase trigger opposing changes in the intracellular distribution of armadillo., Development, 120, 369, 10.1242/dev.120.2.369
1995, Regulation of Spemann organizer formation by the intracellular kinase Xgsk-3., Development, 121, 755, 10.1242/dev.121.3.755
1992, Glycogen synthase kinase-3: Functions in oncogenesis and development., Biochim. Biophys. Acta, 1114, 147
1995, Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled., Development, 121, 1637, 10.1242/dev.121.6.1637
1994, dishevelled is required during wingless signaling to establish both cell polarity and cell identity., Development, 120, 347, 10.1242/dev.120.2.347
1987, Autonomous requirements for the segment polarity gene armadillo during Drosophila embryogenesis., Cell, 49, 117