ID 58585
著者
Takabatake, Shota Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Fukumoto, Yusei Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Ohtsuka, Satomi Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Kanayama, Naoki Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID Kaken ID
Magari, Masaki Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Sakagami, Hiroyuki Department of Anatomy, Kitasato University School of Medicine
Hatano, Naoya Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Tokumitsu, Hiroshi pplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID Kaken ID publons researchmap
抄録
Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) acts as a regulatory kinase that phosphorylates and activates multiple downstream kinases including CaMKI, CaMKIV, 5′AMP-activated protein kinase (AMPK) and protein kinase B (PKB), resulting in regulation of wide variety of Ca2+-dependent physiological responses under normal and pathological conditions. CaMKKβ is regulated by Ca2+/calmodulin-binding, autophosphorylation, and transphosphorylation by multiple protein kinases including cAMP-dependent protein kinase (PKA). In this report, we found that phosphorylation of CaMKKβ is dynamically regulated by protein phosphatase/kinase system in HeLa cells. Global phosphoproteomic analysis revealed the constitutive phosphorylation at 8 Ser residues including Ser128, 132, and 136 in the N-terminal regulatory domain of rat CaMKKβ in unstimulated HeLa cells as well as inducible phosphorylation of Thr144 in the cells treated with a phosphatase inhibitor, okadaic acid (OA). Thr144 phosphorylation in CaMKKβ has shown to be rapidly induced by OA treatment in a time- and dose-dependent manner in transfected HeLa cells, indicating that Thr144 in CaMKKβ is maintained unphosphorylated state by protein phosphatase(s). We confirmed that in vitro dephosphorylation of pThr144 in CaMKKβ by protein phosphatase 2A and 1. We also found that the pharmacological inhibition of protein phosphatase(s) significantly induces CaMKKβ-phosphorylating activity (at Thr144) in HeLa cell lysates as well as in intact cells; however, it was unlikely that this activity was catalyzed by previously identified Thr144-kinases, such as AMPK and PKA. Taken together, these results suggest that the phosphorylation and dephosphorylation of Thr144 in CaMKKβ is dynamically regulated by multiple kinases/phosphatases signaling resulting in fine-tuning of the enzymatic property.
キーワード
CaMKKβ
Phosphorylation
Dephosphorylation
PP1
PP2A
Okadaic acid
備考
This fulltext is available in Feb. 2021.
発行日
2020-04-23
出版物タイトル
Biochemical and Biophysical Research Communications
525巻
1号
出版者
Academic Press
開始ページ
251
終了ページ
257
ISSN
0006-291X
NCID
AA00564395
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
author
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1016/j.bbrc.2020.02.056
助成機関名
文部科学省
助成番号
JP18K06113
JP18K02255
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