Molecular cloning and characterization of WRCH2 on human chromosome 15q15.
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.
Katoh
Masaru
M
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan. mkatoh@ncc.go.jp
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000648:ultrastructure*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D015894:Genome, Human; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010641:Phenotype; D011061:Poly A / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins
D018076:DNA, Complementary; D009363:Neoplasm Proteins; C465202:RHOV protein, human; D012333:RNA, Messenger; D011061:Poly A; D019204:GTP-Binding Proteins; C432668:RHOU protein, human; D020741:rho GTP-Binding Proteins; D002118:Calcium