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

• Published in: The Journal of biological chemistry 2004-08, Vol.279 (35), p.36419-36425
• Main Authors: Kakunaga, Shigeki, Ikeda, Wataru, Shingai, Tatsushi, Fujito, Tsutomu, Yamada, Akio, Minami, Yukiko, Imai, Toshio, Takai, Yoshimi
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Antigens, Neoplasm - metabolism; CD55 Antigens - metabolism; Cell Adhesion Molecules - metabolism; Cell Cycle Proteins - metabolism; Cell Division; Cell Line; Cyclin D2; Cyclin E - metabolism; Cyclin-Dependent Kinase Inhibitor p27; Cyclins - metabolism; Down-Regulation; Fibroblasts - metabolism; Flow Cytometry; G1 Phase; Gene Expression Regulation; Humans; Mice; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogen-Activated Protein Kinases - metabolism; Neoplasm Proteins - metabolism; NIH 3T3 Cells; Platelet-Derived Growth Factor - metabolism; Poliovirus; Proto-Oncogene Proteins c-raf - metabolism; ras Proteins - metabolism; Rats; Resting Phase, Cell Cycle; Retroviridae - genetics; Signal Transduction; Time Factors; Tumor Suppressor Proteins - metabolism; Up-Regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M406340200

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.