Btk29A Promotes Wnt4 Signaling in the Niche to Terminate Germ Cell Proliferation in Drosophila
Btk29A Promotes Wnt4 Signaling in the Niche to Terminate Germ Cell Proliferation in Drosophila
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DOI：
10.1126/science.1244512
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发表时间：
2014-01-17
期刊：
影响因子：
56.9
通讯作者：
Yamamoto, Daisuke
中科院分区：
文献类型：
--
作者：
Hamada-Kawaguchi, Noriko;Nore, Beston F.;Yamamoto, Daisuke
Btk 29 A是哺乳动物布鲁顿酪氨酸激酶（Btk）的果蝇直系同源物，其突变在人类中引起遗传性免疫缺陷疾病。Btk 29 A突变稳定了增殖的成囊细胞的命运，导致卵巢肿瘤。这种表型通过野生型Btk 29 A的过表达而被拯救，并且通过体细胞护送细胞中Wnt 4-β-连环蛋白信号传导或其推定的下游核蛋白Piwi的干扰而被表型化。Btk 29 A和哺乳动物Btk直接磷酸化β-catenin的酪氨酸残基，导致其转录活性上调。因此，我们确定了一个涉及激酶Btk 29 A/Btk及其磷酸化靶点β-连环蛋白的转录开关，该蛋白在护送细胞中的Wnt 4下游发挥作用，通过上调piwi表达来终止果蝇生殖细胞增殖。这种信号传导机制可能代表了一种多功能的发育开关。
Btk29A is the Drosophila ortholog of the mammalian Bruton's tyrosine kinase (Btk), mutations of which in humans cause a heritable immunodeficiency disease. Btk29A mutations stabilized the proliferating cystoblast fate, leading to an ovarian tumor. This phenotype was rescued by overexpression of wild-type Btk29A and phenocopied by the interference of Wnt4-beta-catenin signaling or its putative downstream nuclear protein Piwi in somatic escort cells. Btk29A and mammalian Btk directly phosphorylated tyrosine residues of beta-catenin, leading to the up-regulation of its transcriptional activity. Thus, we identify a transcriptional switch involving the kinase Btk29A/Btk and its phosphorylation target, beta-catenin, which functions downstream of Wnt4 in escort cells to terminate Drosophila germ cell proliferation through up-regulation of piwi expression. This signaling mechanism likely represents a versatile developmental switch.