title: Enhancement of serum- and platelet-derived growth factor-induced cell proliferation by Necl-5/Tage4/poliovirus receptor/CD155 through the Ras-Raf-MEK-ERK signaling.
abstract: Necl-5/Tage4/poliovirus receptor/CD155 has been shown to be the poliovirus receptor and to be up-regulated in rodent and human carcinoma. We have found previously that mouse Necl-5 regulates cell motility. We show here that mouse Necl-5 is furthermore involved in the regulation of cell proliferation. Studies using a specific antibody against Necl-5 and a dominant negative mutant of Necl-5 revealed that Necl-5 enhanced the serum-induced proliferation of NIH3T3, Swiss3T3, and mouse embryonic fibroblast cells. Necl-5 enhanced the serum-induced activation of the Ras-Raf-MEK-ERK signaling, up-regulated cyclins D2 and E, and down-regulated p27(Kip1), eventually shortening the period of the G(0)/G(1) phase of the cell cycle in NIH3T3 cells. Necl-5 similarly enhanced the platelet-derived growth factor-induced activation of the Ras-Raf-MEK-ERK signaling and shortened the period of the G(0)/G(1) phase of the cell cycle in NIH3T3 cells. Necl-5 acted downstream of the platelet-derived growth factor receptor and upstream of Ras. Moreover, up-regulated Necl-5 was involved at least partly in the enhanced proliferation of transformed cells including NIH3T3 cells transformed by an oncogenic Ras or v-Src. These results indicate that Necl-5 plays roles not only in cell motility but also in cell proliferation.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kakunaga
authors.forename: Wataru
authors.initials: W
authors.lastname: Ikeda
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Shingai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujito
authors.forename: Akio
authors.initials: A
authors.lastname: Yamada
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minami
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000378:metabolism*; D018958:CD55 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D056742:Cyclin D2; D019927:Cyclin E / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D016192:Resting Phase, Cell Cycle; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C080336:CCND2 protein, human; D018958:CD55 Antigens; C486196:Ccnd2 protein, mouse; C486197:Ccnd2 protein, rat; C493961:Cdkn1b protein, mouse; C493962:Cdkn1b protein, rat; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D056742:Cyclin D2; D019927:Cyclin E; D016213:Cyclins; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; C476587:Taa1 protein, mouse; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins