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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / chemistry
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Antigens, Neoplasm / metabolism*
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CD55 Antigens / metabolism*
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Cell Adhesion Molecules / metabolism*
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Cell Cycle Proteins / metabolism
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Cell Division
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Cell Line
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Cyclin D2
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Cyclin E / metabolism
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclins / metabolism
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Down-Regulation
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Fibroblasts / metabolism
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Flow Cytometry
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G1 Phase
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Gene Expression Regulation
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Humans
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Mice
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / metabolism
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NIH 3T3 Cells
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Neoplasm Proteins / metabolism*
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Platelet-Derived Growth Factor / metabolism*
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Proto-Oncogene Proteins c-raf / metabolism
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Rats
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Resting Phase, Cell Cycle
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Retroviridae / genetics
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Signal Transduction
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Time Factors
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Tumor Suppressor Proteins / metabolism
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Up-Regulation
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ras Proteins / metabolism
Substances
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Antibodies, Monoclonal
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Antigens, Neoplasm
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CCND2 protein, human
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CD55 Antigens
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Ccnd2 protein, mouse
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Ccnd2 protein, rat
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Cdkn1b protein, mouse
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Cdkn1b protein, rat
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Cell Adhesion Molecules
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Cell Cycle Proteins
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Cyclin D2
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Cyclin E
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Cyclins
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Neoplasm Proteins
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Platelet-Derived Growth Factor
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Taa1 protein, mouse
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Proto-Oncogene Proteins c-raf
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Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase Kinases
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ras Proteins