A new phosphorylation site in cardiac L-type Ca<sup>2+</sup> channels (Cav1.2) responsible for its cAMP-mediated modulation
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- Etsuko Minobe
- Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan;
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- Sachiko Maeda
- Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan;
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- Liying Hao
- Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan;
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- Jianjun Xu
- Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan;
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- Asako Kameyama
- Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan;
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- Masaki Kameyama
- Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan;
書誌事項
- 公開日
- 2014-12-01
- 資源種別
- journal article
- DOI
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- 10.1152/ajpcell.00267.2014
- 公開者
- American Physiological Society
この論文をさがす
説明
<jats:p> Cardiac L-type Ca<jats:sup>2+</jats:sup> channels are modulated by phosphorylation by protein kinase A (PKA). To explore the PKA-targeted phosphorylation site(s), five potential phosphorylation sites in the carboxyl (COOH) terminal region of the α<jats:sub>1C</jats:sub>-subunit of the guinea pig Cav1.2 Ca<jats:sup>2+</jats:sup> channel were mutated by replacing serine (S) or threonine (T) residues with alanine (A): S1574A (C1 site), S1626A (C2), S1699A (C3), T1908A, (C4), S1927A (C5), and their various combinations. The wild-type Ca<jats:sup>2+</jats:sup> channel activity was enhanced three- to fourfold by the adenylyl cyclase activator forskolin (Fsk, 5 μM), and that of mutants at C3, C4, C5, and combination of these sites was also significantly increased by Fsk. However, Fsk did not modulate the activity of the C1 and C2 mutants and mutants of combined sites involving the C1 site. Three peptides of the COOH-terminal tail of α<jats:sub>1C</jats:sub>, termed CT1 [corresponding to amino acids (aa) 1509–1789, containing sites C1–3], CT2 (aa 1778–2003, containing sites C4 and C5), and CT3 (aa 1942–2169), were constructed, and their phosphorylation by PKA was examined. CT1 and CT2, but not CT3, were phosphorylated in vitro by PKA. Three CT1 mutants at two sites of C1-C3 were also phosphorylated by PKA, but the mutant at all three sites was not. The CT2 mutant at the C4 site was phosphorylated by PKA, but the mutant at C5 sites was not. These results suggest that Ser<jats:sup>1574</jats:sup> (C1 site) may be a potential site for the channel modulation mediated by PKA. </jats:p>
収録刊行物
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- American Journal of Physiology-Cell Physiology
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American Journal of Physiology-Cell Physiology 307 (11), C999-C1009, 2014-12-01
American Physiological Society
