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):977-82.
WNT signals are transduced to the JNK pathway, the Ca2+-releasing pathway, or the beta-catenin - TCF pathway through seven-transmembrane-type WNT receptors encoded by Frizzled genes (FZD1-FZD10). WRCH1/ARHV and CDC42 are potentially implicated in the WNT-JNK pathway. Here, WRCH2/ARHV cDNAs were isolated by using bioinformatics and cDNA-PCR. WRCH2 gene, consisting of at least 3 exons, encoded a 236-amino-acid protein with proline-rich domain and GTPase domain. WRCH2 was homologous to WRCH1 (55.4% total-amino-acid identity) and CDC42 (43.5% total-amino-acid identity). WRCH2 gene was located on human chromosome 15q15, which is one of fragile sites in the human genome. A single nucleotide substitution (632 Gright curved arrow A) was identified between WRCH2 cDNA and human genome draft sequences, which resulted in Arg177Lys amino-acid substitution. WRCH2 mRNA was relatively highly expressed in pancreas, placenta, and fetal brain. WRCH2 mRNA was over-expressed in TMK1 (gastric cancer), Hs700T (pancreatic cancer), HeLa S3 (cervical cancer), and A549 (lung cancer). WRCH2 mRNA was moderately expressed in MKN74, MKN45, MKN28, KATO-III (gastric cancer), HL-60 (pro-myelocytic leukemia), Raji (Burkitt's lymphoma), and SW480 (colorectal cancer). WRCH2 mRNA was up-regulated in 3 out of 8 cases of primary gastric cancer. Because Wrch1 can activate PAK1 and JNK1, and induce filopodium formation and stress fiber dissolution, over-expression of WRCH2 mRNA in human cancer cells might also lead to more malignant phenotype.
WNT信号通过由卷曲蛋白基因（FZD1 - FZD10）编码的七跨膜型WNT受体转导至JNK途径、Ca2+释放途径或β-连环蛋白 - TCF途径。WRCH1/ARHV和CDC42可能参与WNT - JNK途径。在此，通过生物信息学和cDNA - PCR分离出了WRCH2/ARHV cDNA。WRCH2基因至少由3个外显子组成，编码一种含有富含脯氨酸结构域和GTPase结构域的236个氨基酸的蛋白质。WRCH2与WRCH1同源（总氨基酸同一性为55.4%），与CDC42同源（总氨基酸同一性为43.5%）。WRCH2基因位于人类染色体15q15上，这是人类基因组中的脆性位点之一。在WRCH2 cDNA与人类基因组草图序列之间鉴定出一个单核苷酸替换（632 G→A），这导致了Arg177Lys氨基酸替换。WRCH2 mRNA在胰腺、胎盘和胎儿脑中相对高表达。WRCH2 mRNA在TMK1（胃癌）、Hs700T（胰腺癌）、HeLa S3（宫颈癌）和A549（肺癌）中过表达。WRCH2 mRNA在MKN74、MKN45、MKN28、KATO - III（胃癌）、HL - 60（早幼粒细胞白血病）、Raji（伯基特淋巴瘤）和SW480（结直肠癌）中中度表达。在8例原发性胃癌中有3例WRCH2 mRNA上调。由于Wrch1可激活PAK1和JNK1，并诱导丝状伪足形成和应力纤维溶解，因此WRCH2 mRNA在人类癌细胞中的过表达可能也会导致更恶性的表型。
