Wnt signaling stabilizes the dual-function protein β-catenin in diverse cell types
Wnt signaling stabilizes the dual-function protein β-catenin in diverse cell types
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DOI：
10.1111/j.1749-6632.1998.tb10106.x
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Brown, AMC
中科院分区：
文献类型：
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作者：
Giarré, M;Semënov, MV;Brown, AMC
Wnt蛋白是一个分泌型信号传导因子大家族，在胚胎和出生后发育过程中具有多种诱导和调节功能。在哺乳动物中，这些包括在中枢神经系统、肾脏、四肢和乳腺的形态发生中的关键作用。近年来，通过对果蝇、C. elegans线虫，Xenopus爪蟾，and mammalian哺乳动物systems系统.这一途径的几个特征在进化中非常保守。Wnt途径的关键组分是细胞质蛋白β-连环蛋白，其稳定性由于Wnt信号传导而增加。虽然Wnt-1在细胞培养中的形态学效应只出现在有限数量的细胞系中，但我们在这里表明，在生物化学水平上对Wnt-1的反应是上皮细胞和间充质细胞的共同特性。β-连环蛋白丰度的增加可能具有至少两种功能性后果，这取决于蛋白质的亚细胞定位。在一些对Wnt-1有反应的细胞系中，与质膜相关的β-连环蛋白部分显著增加，其中该蛋白质充当细胞-细胞粘附连接的组分。在其他细胞类型中，Wnt信号传导的主要作用是β-连环蛋白的胞质池的增加。最近，该库的丰度增加与β-连环蛋白进入细胞核相关，在细胞核中该蛋白与Tcf转录因子形成复合物，并被认为调节特定基因的表达。Wnt信号对细胞粘附和/或基因表达的双重影响提供了至少两种潜在的机制，通过这种机制，这一关键途径可以在形态发生的调节中发挥作用。
The Wnt proteins constitute a large family of secreted signaling factors that perform a wide variety of inductive and regulatory functions in embryonic and postnatal development. In mammals, these include crucial roles in morphogenesis of the central nervous system, kidneys, limbs, and mammary glands. In recent years, much progress has been made in identifying components of the intracellular Wnt-1 signal transduction pathway through studies in Drosophila, C. elegans, Xenopus, and mammalian systems. Several features of this pathway are remarkably well conserved in evolution. A key component of the Wnt pathway is the cytoplasmic protein beta-catenin, whose stability is increased as a result of Wnt signaling. Although morphological effects of Wnt-1 in cell culture are seen in only a limited number of cell lines, we show here that responsiveness to Wnt-1 at the biochemical level is a common property of both epithelial and mesenchymal cells. The increased abundance of beta-catenin may have at least two functional consequences, depending on the subcellular localization of the protein. In some cell lines that respond to Wnt-1, there is a significant increase in the beta-catenin fraction associated with the plasma membrane, where the protein acts as a component of cell-cell adhesive junctions. In other cell types, the major effect of Wnt signaling is an increase in the cytosolic pool of beta-catenin. Increased abundance of this pool has recently been correlated with entry of beta-catenin into the nucleus, where the protein forms complexes with Tcf transcription factors and is thought to modulate the expression of specific genes. The dual consequences of Wnt signaling on cell adhesion and/or gene expression provide at least two potential mechanisms by which this key pathway can function in the regulation of morphogenesis.