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标题：Role of extracellular subdomains of p185c-neu and the epidermal growth factor receptor in ligand-independent association and transactivation
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作者：Toru Kumagai ; Makoto Katsumata ; Akihiro Hasegawa 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：16
页码：9220-9225
DOI：10.1073/pnas.1633546100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We investigated the assembly and activation of the epidermal growth factor receptor (EGFR)-p185c-neu heterodimer by using a sequential immunoprecipitation methodology. Using this approach we detected heterodimers and also higher-ordered oligomeric complexes. Phosphorylated EGFR-p185c-neu heterodimeric forms were detected in the absence of EGF, but the species became highly phosphorylated after EGF stimulation. To evaluate heterodimer formation and additional transactivation by EGF, we investigated the roles of the four extracellular subdomains of p185c-neu and the EGFR. Subdomains I-IV of the EGFR dimerized with subdomains I-IV of p185c-neu, respectively, in a parallel manner. In addition, subdomains I-IV of the EGFR also associated with p185c-neu subdomains III, IV, I, and II, respectively. A lack of one of the p185c-neu cysteine-rich domains (subdomains II or IV) resulted in a loss of EGF-induced transactivation. These data suggest that two cysteine-rich domains play defining roles in ligand-dependent transactivation and that both of these cysteine-rich extracellular subdomains as well as non-cysteine-rich extracellular subdomains are involved in ligand-independent interactions with the EGFR. Our studies provide biochemical evidence of the role of the cysteine-rich domains of p185c-neu in assembly and transactivation of erbB complexes and also indicate that these subdomains might be useful clinical targets.
关键词：heterodimer ; cysteine-rich domain