Katoh Yuriko, Katoh Masaru
M and M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Oncol. 2005 May;26(5):1435-40.
WNT signals are transduced to the beta-catenin pathway or the planar cell polarity (PCP) pathway. WNT - beta-catenin pathway is implicated in carcinogenesis, while WNT-PCP pathway is implicated in cell motility and metastasis. Drosophila Van Gogh (Vang), Frizzled (Fz), Starry night (Stan), Prickle (Pk) and Diego (Dgo) are PCP signaling molecules. Vangl1 (Strabismus 2) and Vangl2 (Strabismus 1 or Ltap) are mammalian homologs of Drosophila Vang interacting with PRICKLE1, PRICKLE2, ANKRD6, DVL1, DVL2, DVL3, KAI1 and MAGI3. Here we identified and characterized rat Vangl1 and Vangl2 genes by using bioinformatics. Rat Vangl1 gene, consisting of eight exons, was located within AC098913.7 and AC108524.6 genome sequences. Rat Vangl2 gene, consisting of eight exons, was located within AC118856.3 and AC115243.5 genome sequences. Exon-intron structure of mammalian Vangl1 and Vangl2 orthologs was well conserved. E47 and double ELK1-binding sites were conserved among promoters of mammalian Vangl1 orthologs. PAX4, NFkappaB, HNF4, SOX9, RFX1, and POU2F1 (OCT1)-binding sites were conserved among promoters of mammalian Vangl2 orthologs. Rat Vangl1 (526 aa) and Vangl2 (521 aa) were four-transmembrane proteins with 71.5% total-amino-acid identity. Ser cluster motif (SxxSxxSxxSxxSxxS) in the N-terminal cytoplasmic region and PDZ-binding motif in the C-terminal cytoplasmic tail were evolutionarily conserved among vertebrate Vangl1 and Vangl2 orthologs. This is the first report on rat Vangl1 and Vangl2 genes as well as on comparative genomics for Vangl1 and Vangl2 orthologs.
WNT信号被转导至β-连环蛋白通路或平面细胞极性(PCP)通路。WNT-β-连环蛋白通路与癌症发生有关,而WNT-PCP通路与细胞运动和转移有关。果蝇中的梵高(Vang)、卷曲蛋白(Fz)、星夜(Stan)、刺蛋白(Pk)和迭戈(Dgo)是PCP信号分子。Vangl1(斜视2)和Vangl2(斜视1或Ltap)是果蝇Vang的哺乳动物同源物,它们与PRICKLE1、PRICKLE2、ANKRD6、DVL1、DVL2、DVL3、KAI1和MAGI3相互作用。在此,我们通过生物信息学方法鉴定并表征了大鼠Vangl1和Vangl2基因。大鼠Vangl1基因由八个外显子组成,位于AC098913.7和AC108524.6基因组序列内。大鼠Vangl2基因由八个外显子组成,位于AC118856.3和AC115243.5基因组序列内。哺乳动物Vangl1和Vangl2直系同源物的外显子-内含子结构高度保守。E47和双ELK1结合位点在哺乳动物Vangl1直系同源物的启动子中保守。PAX4、NFκB、HNF4、SOX9、RFX1和POU2F1(OCT1)结合位点在哺乳动物Vangl2直系同源物的启动子中保守。大鼠Vangl1(526个氨基酸)和Vangl2(521个氨基酸)是具有71.5%总氨基酸同一性的四跨膜蛋白。N端细胞质区域的丝氨酸簇基序(SxxSxxSxxSxxSxxS)和C端细胞质尾巴中的PDZ结合基序在脊椎动物Vangl1和Vangl2直系同源物中进化保守。这是关于大鼠Vangl1和Vangl2基因以及Vangl1和Vangl2直系同源物比较基因组学的首次报道。