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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kishimoto, Megumi Ikeda, Wataru Takai, Yoshimi Kawano, Satoshi Ogita, Hisakazu |
| Description | Author Affiliation: Kawano S ( Division of Molecular and Cellular Biology, Department of Biochemistry, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan.) |
| Abstract | ErbB2 and ErbB3, members of the EGF receptor/ErbB family, form a heterodimer upon binding of a ligand, inducing the activation of Rac small G protein and Akt protein kinase for cell movement and survival, respectively. The enhanced ErbB3/ErbB2 signaling causes tumorigenesis, invasion, and metastasis. We found here that the ErbB3/ErbB2 signaling is regulated by immunoglobulin-like Necl-2, which is down-regulated in various cancer cells and serves as a tumor suppressor. The extracellular region of ErbB3, but not ErbB2, interacted in cis with that of Necl-2. This interaction reduced the ligand-induced, ErbB2-catalyzed tyrosine phosphorylation of ErbB3 and inhibited the consequent ErbB3-mediated activation of Rac and Akt, resulting in the inhibition of cancer cell movement and survival. These inhibitory effects of Necl-2 were mediated by the protein-tyrosine phosphatase PTPN13 which interacted with the cytoplasmic tail of Necl-2. We describe here this novel mechanism for silencing of the ErbB3/ErbB2 signaling by Necl-2. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 35 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-08-28 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Immunoglobulins Metabolism Membrane Proteins Receptor, ErbB-2 Receptor, ErbB-3 Signal Transduction Animals Cell Adhesion Molecules Cell Line Dimerization Genetics Mice Mice, Inbred C57BL Phosphorylation Protein Binding Chemistry Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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