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Inactivation of Ca 2+ /calmodulin‐dependent protein kinase I by S ‐glutathionylation of the active‐site cysteine residue
Author(s) -
Kambe Toshie,
Song Tao,
Takata Tsuyoshi,
Hatano Naoya,
Miyamoto Yoshiaki,
Nozaki Naohito,
Naito Yasuhito,
Tokumitsu Hiroshi,
Watanabe Yasuo
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.04.059
Subject(s) - calmodulin , cysteine , glutathione , protein kinase a , biochemistry , enzyme , chemistry , kinase , mutagenesis , signal transduction , mutant , gene
We show that Ca 2+ /calmodulin(CaM)‐dependent protein kinase I (CaMKI) is directly inhibited by its S ‐glutathionylation at the Cys 179 . In vitro studies demonstrated that treatment of CaMKI with diamide and glutathione results in inactivation of the enzyme, with a concomitant S ‐glutathionylation of CaMKI at Cys 179 detected by mass spectrometry. Mutagenesis studies confirmed that S ‐glutathionylation of Cys 179 is both necessary and sufficient for the inhibition of CaMKI by diamide and glutathione. In transfected cells expressing CaMKI, treatment with diamide caused a reversible decrease in CaMKI activity. Cells expressing mutant CaMKI (179CV) proved resistant in this regard. Thus, our results indicate that the reversible regulation of CaMKI via its modification at Cys 179 is an important mechanism in processing calcium signal transduction in cells.