Wnt11/5a Complex Formation Caused by Tyrosine Sulfation Increases Canonical Signaling Activity
Wnt11/5a Complex Formation Caused by Tyrosine Sulfation Increases Canonical Signaling Activity
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DOI：
10.1016/j.cub.2009.07.062
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发表时间：
2009-09-29
期刊：
影响因子：
9.2
通讯作者：
Heasman, Janet
中科院分区：
文献类型：
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作者：
Cha, Sang-Wook;Tadjuidje, Emmanuel;Heasman, Janet
Wnt信号传导在胚胎发育、组织分化和癌症中起重要作用[1-7]。在正常和恶性组织中，Wnt家族成员通常组合表达[8-11]，尽管其意义尚不清楚。我们最近发现，Wnt 11和Wnt 5a都是启动胚胎轴形成所必需的，并且这两种蛋白质相互作用[12]。然而，很少有人知道Wnt-Wnt蛋白相互作用的机制或生物学意义。在这里，我们表明，在三个试验中，与非洲爪蟾卵母细胞，小鼠L细胞，和人类胚胎干细胞，分泌非洲爪蟾Wnt 11/5a复合物有更多的典型Wnt信号传导活性比分泌Wnt 11或Wnt 5a单独行动。我们表明，酪蛋白磺基转移酶-1（TPST-1）的硫酸化活性是非洲爪蟾背轴形成所必需的，并且特定酪氨酸残基的O-硫酸化对于Wnt 11与Wnt 5a的相互作用和增强的典型信号传导活性是必要的。这些发现表明了Wnt生物学的一个新的方面Wnt家族成员的相互作用，依赖于酪氨酰硫酸化。
Wnt signaling plays important roles in embryonic development, tissue differentiation, and cancer [1-7]. In both normal and malignant tissue, Wnt family members are often expressed combinatorially [8-11], although the significance of this is not understood. We recently showed that Wnt11 and Wnt5a are both required for the initiation of embryonic axis formation and that the two proteins physically interact with each other [12]. However, little is known about the mechanism or biological significance of Wnt-Wnt protein interaction. Here we show in three assays, with Xenopus oocytes, mouse L cells, and human embryonic stem cells, that secreted Xenopus Wnt11/5a complexes have more canonical Wnt signaling activity than secreted Wnt11 or Wnt5a acting alone. We demonstrate that the sulfation activity of tyrosylprotein sulfotransferase-1 (TPST-1) is required for Xenopus dorsal axis formation and that O-sulfation of specific tyrosine residues is necessary for the interaction of Wnt11 with Wnt5a and for enhanced canonical signaling activity. These findings demonstrate a novel aspect of Wnt biology-Wnt family member interaction that depends on tyrosyl sulfation.