著者

Eiji Hiraoka Kengo Tanabe Shinichiro Izuta Tadao Kubota Shun Kohsaka Amane Kozuki Kazuhiro Satomi Hiroki Shiomi Toshiro Shinke Toshiyuki Nagai Susumu Manabe Yasuhide Mochizuki Taku Inohara Mitsuhiko Ota Tetsuma Kawaji Yutaka Kondo Yumiko Shimada Yohei Sotomi Tomofumi Takaya Atsushi Tada Tomohiko Taniguchi Kazuya Nagao Kenichi Nakazono Yukiko Nakano Kazuhiko Nakayama Yuichiro Matsuo Takashi Miyamoto Yoshinao Yazaki Kazuyuki Yahagi Takuya Yoshida Kohei Wakabayashi Hideki Ishii Minoru Ono Akihiro Kishida Takeshi Kimura Tetsuro Sakai Yoshihiro Morino on behalf of the Japanese Society Joint Working Group

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-22-0609, (Released:2023-08-10)

参考文献数

439

被引用文献数

6

著者

Hideyuki Yamamoto Sayomi Higa-Nakamine Nobuhiro Noguchi Noriko Maeda Yutaka Kondo Seikichi Toku Ichiro Kukita Kazuhiro Sugahara

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

pp.13R11CP, (Released:2014-02-19)

参考文献数

28

被引用文献数

2 15

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Four transmembrane tyrosine kinases constitute the ErbB protein family: epidermal growth factor receptor (EGFR) or ErbB1, ErbB2, ErbB3, and ErbB4. In general, the structure and mechanism of the activation of these members are similar. However, significant differences in homologous desensitization are known between EGFR and ErbB4. Desensitization of ligand-occupied EGFR occurs by endocytosis, while that of ErbB4 occurs by selective cleavage at the cell surface. Because ErbB4 is abundantly expressed in neurons from fetal to adult brains, elucidation of the desensitization mechanism is important to understand neuronal development and synaptic functions. Recently, it has become clear that heterologous desensitization of EGFR and ErbB4 are induced by endocytosis and cleavage, respectively, similar to homologous desensitization. It has been reported that heterologous desensitization of EGFR is induced by serine phosphorylation of EGFR via the p38 mitogen-activated protein kinase (p38 MAP kinase) pathway in various cell lines, including alveolar epithelial cells. In contrast, the protein kinase C pathway is involved in ErbB4 cleavage. In this review, we will describe recent advances in the desensitization mechanisms of EGFR and ErbB4, mainly in alveolar epithelial cells and hypothalamic neurons, respectively.