教員業績データベース |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読なし |
表題 | CCM2 and PAK4 act downstream of atrial natriuretic peptide signaling to promote cell spreading |
掲載誌名 | 正式名:The Biochemical journal 略 称:Biochem J ISSNコード:1470-8728(Electronic)0264-6021(Linking) |
掲載区分 | 国外 |
巻・号・頁 | 474(11),pp.1897-918 |
著者・共著者 | Miura Koichi, Nojiri Takashi, Akitake Yoshiharu, Ando Koji, Fukuhara Shigetomo, Zenitani Masahiro, Kimura Toru, Hino Jun, Miyazato Mikiya, Hosoda Hiroshi, Kangawa Kenji |
発行年月 | 2017/05 |
概要 | Atrial natriuretic peptide (ANP) is a cardiac hormone released by the atrium in response to stretching forces. Via its receptor, guanylyl cyclase-A (GC-A), ANP maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and hypotensive effects mediated, in part, by endothelial cells. Both in vivo and in vitro, ANP enhances endothelial barrier function by reducing RhoA activity and reorganizing the actin cytoskeleton. We established mouse endothelial cells that stably express GC-A and used them to analyze the molecular mechanisms responsible for actin reorganization. Stimulation by ANP resulted in phosphorylation of myosin light chain (MLC) and promotion of cell spreading. p21-activated kinase 4 (PAK4) and cerebral cavernous malformations 2 (CCM2), a scaffold protein involved in a cerebrovascular disease, were required for the phosphorylation of MLC and promotion of cell spreading by ANP. Finally, in addition to the GC domain, the kinase homology domain of GC-A was also required for ANP/GC-A signaling. Our results indicate that CCM2 and PAK4 are important downstream mediators of ANP/GC-A signaling involved in cell spreading, an important initial step in the enhancement of endothelial barrier function. |
DOI | 10.1042/BCJ20160841 |
PMID | 28432261 |