Molecular cloning and characterization of FRAT2, encoding a positive regulator of the WNT signaling pathway
Molecular cloning and characterization of FRAT2, encoding a positive regulator of the WNT signaling pathway
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DOI：
10.1006/bbrc.2001.4421
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发表时间：
2001-03-02
影响因子：
3.1
通讯作者：
Katoh, M
中科院分区：
文献类型：
--
作者：
Saitoh, T;Moriwaki, J;Katoh, M
FRAT1通过与糖原合成酶-3β结合来稳定β-连环蛋白，从而正向调节WNT信号通路。在这里，我们从人胎肺的cDNA文库中克隆了FRAT2的cDNAs，其编码序列完整。FRAT2编码233个氨基酸，与FRAT1的氨基酸同源性为77.3%。FRAT2和FRAT1在酸性结构域(96%的同源性)、富含Pro的结构域(92%的同源性)和GSK-3的β结合结构域(100%的同源性)上有更高的同源性。FRAT2基因定位于人类染色体10q24.1。在MKN45(胃癌)、HeLa S3(宫颈癌)和K-562(慢性粒细胞白血病)中，2.4kb的FRAT2mRNA表达水平较高。Xenopus轴复制分析表明，野生型FRAT2具有诱导次生轴的能力，而缺失酸性结构域和富含Pro结构域的突变型FRAT2不具有诱导次生轴的能力。这些结果表明，FRATS和FRAT1一样，是WNT信号通路的正向调节因子。因此，FRAT2在人类癌症中的上调可能通过激活WNT信号通路而参与肿瘤的发生。(C)2001年学术出版社。
FRAT1 positively regulates the WNT signaling pathway by stabilizing beta -catenin through the association with glycogen synthase kinase-3 beta. Here, we have cloned FRAT2 cDNAs, spanning the complete coding sequence, from a human fetal lung cDNA library. FRAT2 encoded 233 amino-acid protein, which showed 77.3% total amino-acid identity with FRAT1. FRAT2 and FRAT1 were more homologous in the acidic domain (96% identity), the proline-rich domain (92% identity), and the GSK-3 beta binding domain (100% identity). The FRAT2 gene was mapped to human chromosome 10q24.1. The FRAT2 mRNA of 2.4-kb in size was relatively highly expressed in MKN45 (gastric cancer), HeLa S3 (cervical cancer), and K-562 (chronic myelogenous leukemia). Xenopus axis duplication assay revealed that the wild-type FRAT2 mRNA,but not the mutant FRAT2 mRNA lacking the acidic domain and the proline-rich domain, has the capacity to induce the secondary axis. These results indicate that FRATS, just like FRAT1, functions as a positive regulator of the WNT signaling pathway. Thus, up-regulation of FRAT2 in human cancer might be implicated in carcinogenesis through activation of the WNT signaling pathway. (C) 2001 Academic Press.