Katoh Masaru
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Int J Oncol. 2002 May;20(5):993-8.
WNT signaling pathway is implicated in carcinogenesis and embryogenesis. WNT signal is transduced to the beta-catenin - TCF pathway, the JNK pathway, or the Ca2+-releasing pathway through seven-transmembrane-type WNT receptors encoded by Frizzled (FZD) genes. Xenopus Strabismus (Stbm) is a tetra-spanning transmembrane protein interacting with Dishevelled, and is a negative regulator of the WNT - beta-catenin - TCF signaling pathway. STB1/KIAA1215/VANGL2 is a human orthologue of Xenopus Stbm (90.6% total-amino-acid identity). Here, STB2/VANGL1 gene fragments were identified in human genome draft sequences by using bioinformatics, and STB2 cDNAs were isolated by using cDNA-PCR. STB2 gene consisted of at lest 7 exons, and encoded a 524-amino-acid protein with 4 transmembrane domains and the C-terminal Ser/Thr-X-Val motif. Human STB2 was homologous to human STB1 (73.1% total-amino-acid identity) and Xenopus Stbm (72.7% total-amino-acid identity). STB2 gene was clustered with Calsequestrin 2 (CASQ2) gene in tail-to-tail manner (interval less than 5.0 kb), and CASQ2 gene is mapped to human chromosome 1p11-p13.3 or linked to human chromosome 1p13-p21. STB2 mRNAs of 4.8- and 6.8-kb in size were expressed almost ubiquitously in various normal tissues. STB2 mRNA was significantly up-regulated in gastric cancer cell lines MKN28, MKN74, pancreatic cancer cell lines BxPC-3, PSN-1 and Hs766T. On the other hand, STB2 mRNA was significantly down-regulated in a pancreatic cancer cell line AsPC-1. This is the first report on molecular cloning and characterization of STB2.
WNT信号通路与肿瘤发生和胚胎发育有关。WNT信号通过由卷曲蛋白（FZD）基因编码的七跨膜型WNT受体转导至β-连环蛋白-TCF通路、JNK通路或Ca2+释放通路。非洲爪蟾斜视蛋白（Stbm）是一种与散乱蛋白相互作用的四跨膜蛋白，是WNT-β-连环蛋白-TCF信号通路的负调节因子。STB1/KIAA1215/VANGL2是非洲爪蟾Stbm的人类同源物（总氨基酸同一性为90.6%）。在此，通过生物信息学在人类基因组草图序列中鉴定出STB2/VANGL1基因片段，并通过cDNA-PCR分离出STB2 cDNA。STB2基因至少由7个外显子组成，编码一个含4个跨膜结构域和C末端丝氨酸/苏氨酸-X-缬氨酸基序的524个氨基酸的蛋白质。人类STB2与人类STB1同源（总氨基酸同一性为73.1%），与非洲爪蟾Stbm同源（总氨基酸同一性为72.7%）。STB2基因与肌集钙蛋白2（CASQ2）基因以尾对尾的方式成簇（间隔小于5.0 kb），且CASQ2基因定位于人类染色体1p11-p13.3或与人类染色体1p13-p21连锁。大小为4.8 kb和6.8 kb的STB2 mRNA在各种正常组织中几乎普遍表达。在胃癌细胞系MKN28、MKN74、胰腺癌细胞系BxPC-3、PSN-1和Hs766T中，STB2 mRNA显著上调。另一方面，在胰腺癌细胞系AsPC-1中，STB2 mRNA显著下调。这是关于STB2分子克隆和特性的首次报道。
