TY - JOUR
T1 - Persulfide signaling in stress-initiated calmodulin kinase response
AU - Takata, Tsuyoshi
AU - Araki, Shoma
AU - Tsuchiya, Yukihiro
AU - Watanabe, Yasuo
N1 - Funding Information:
This work was supported, in part, by a Grant-in-Aid for Scientific Research on Innovative Areas ‘‘Oxygen Biology: a new criterion for integrated understanding of life’’ (No. 26111008; Y.W.); JSPS KAKENHI Grants-in-Aid for Scientific Research (C) and Young Scientists (B); Program for the Strategic Research Foundation at Private Universities (No. S1311012; Y.T and Y.W.) of the MEXT, Japan; and Grant-in-Aid from the Showa Pharmaceutical University for Young Scientists (R1-2—S.A.; H27-3, H28-2—T.T.; H23-2—Y.T.).
Publisher Copyright:
ª Mary Ann Liebert, Inc.
PY - 2020/12/20
Y1 - 2020/12/20
N2 - Significance: Calcium ion (Ca2+)/calmodulin (CaM)-dependent protein kinases (CaMKs) are activated by phosphorylation of a crucial threonine residue either by itself (CaMKII) or by upstream kinases, CaMK kinases (CaMKKs) (CaMKI and CaMKIV). CaMKs, present in most mammalian tissues, can phosphorylate many downstream targets, thereby regulating numerous cellular functions. Recent Advances: Aside from canonical post-translational modifications, cysteine-based redox switches in CaMKs affect their enzyme activities. In addition to reactive oxygen species (ROS) and reactive nitrogen species (RNS), reactive sulfur species (RSS) are also recognized as key signaling molecules, regulating protein function through polysulfidation, formation of polysulfides [-S-(S)n-H] on their reactive cysteine residues. To comprehend the biological significance of RSS signaling-related CaMK regulation, here we introduce a novel concept defining CaMKs as RSS targets in stress responses. The stress responses include an irreversible electrophile attack for CaMKI, inflammation for CaMKII, and endoplasmic reticulum stress for CaMKIV. Critical Issues: Development of various human diseases is associated with increased ROS, RNS, and RSS generation. Therefore, depending on specific pathophysiology, RSS could have very particular effects on CaMK functions. Future Directions: How multiple sources and mutual reactions of ROS, RNS, and RSS are coordinated is obscure. Elucidating the mechanisms through applications of enzymology, chemical biology, and mass spectrometry enables to uncover the complexities of redox regulation of CaMK cascades. Antioxid. Redox Signal. 33, 1308–1319.
AB - Significance: Calcium ion (Ca2+)/calmodulin (CaM)-dependent protein kinases (CaMKs) are activated by phosphorylation of a crucial threonine residue either by itself (CaMKII) or by upstream kinases, CaMK kinases (CaMKKs) (CaMKI and CaMKIV). CaMKs, present in most mammalian tissues, can phosphorylate many downstream targets, thereby regulating numerous cellular functions. Recent Advances: Aside from canonical post-translational modifications, cysteine-based redox switches in CaMKs affect their enzyme activities. In addition to reactive oxygen species (ROS) and reactive nitrogen species (RNS), reactive sulfur species (RSS) are also recognized as key signaling molecules, regulating protein function through polysulfidation, formation of polysulfides [-S-(S)n-H] on their reactive cysteine residues. To comprehend the biological significance of RSS signaling-related CaMK regulation, here we introduce a novel concept defining CaMKs as RSS targets in stress responses. The stress responses include an irreversible electrophile attack for CaMKI, inflammation for CaMKII, and endoplasmic reticulum stress for CaMKIV. Critical Issues: Development of various human diseases is associated with increased ROS, RNS, and RSS generation. Therefore, depending on specific pathophysiology, RSS could have very particular effects on CaMK functions. Future Directions: How multiple sources and mutual reactions of ROS, RNS, and RSS are coordinated is obscure. Elucidating the mechanisms through applications of enzymology, chemical biology, and mass spectrometry enables to uncover the complexities of redox regulation of CaMK cascades. Antioxid. Redox Signal. 33, 1308–1319.
KW - Ca/calmodulin-dependent protein kinase (CaMK)
KW - Cysteine-based redox switches
KW - Phosphorylation
KW - Polysulfidation
KW - Reactive sulfur species (RSS)
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U2 - 10.1089/ars.2020.8138
DO - 10.1089/ars.2020.8138
M3 - Review article
C2 - 32460522
AN - SCOPUS:85093885957
VL - 33
SP - 1308
EP - 1319
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 18
ER -