TY - JOUR
T1 - Calcium/calmodulin-dependent protein kinases as potential targets of nitric oxide
AU - Takata, Tsuyoshi
AU - Kimura, Jun
AU - Tsuchiya, Yukihiro
AU - Naito, Yasuhito
AU - Watanabe, Yasuo
N1 - Funding Information:
This work was supported in part by a Grants-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (Y.W.), from the Smoking Research Foundation (Y.W.) and from the Japan-China Medical Association (Y.W.). We thank Dr. Malcolm Moore for critical reading of the manuscript.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - Nitric oxide (NO) synthesis is controlled by Ca 2+/calmodulin (CaM) binding with and kinase-dependent phosphorylation of constitutive NO synthases, which catalyze the formation of NO and l-citrulline from l-arginine. NO operates as a mediator of important cell signaling pathways, such as cGMP signaling cascade. Another mechanism by which NO exerts biological effects is mediated via post-translational modification of redox-sensitive cysteine thiols of proteins. The Ca 2+/CaM-dependent protein kinases (CaM kinases) such as CaM kinase I, CaM kinase II, and CaM kinase IV, are a family of protein kinases which requires binding of Ca 2+/CaM to and subsequent phosphorylation of the enzymes to initiate its activation process. We report other regulation mechanisms of CaM kinases, such as S-glutathionylation of CaM kinase I at Cys 179 and S-nitrosylation of CaM kinase II at Cys 6/30. Such unique post-translational modification of CaMKs by NO shed light on a new area of mutual regulation of NO- and CaM kinases-signals. Based on the novel direct regulation of these kinases, we propose that CaM kinases/NO signaling would be good targets for understanding how they can participate in neuronal physiology and disease.
AB - Nitric oxide (NO) synthesis is controlled by Ca 2+/calmodulin (CaM) binding with and kinase-dependent phosphorylation of constitutive NO synthases, which catalyze the formation of NO and l-citrulline from l-arginine. NO operates as a mediator of important cell signaling pathways, such as cGMP signaling cascade. Another mechanism by which NO exerts biological effects is mediated via post-translational modification of redox-sensitive cysteine thiols of proteins. The Ca 2+/CaM-dependent protein kinases (CaM kinases) such as CaM kinase I, CaM kinase II, and CaM kinase IV, are a family of protein kinases which requires binding of Ca 2+/CaM to and subsequent phosphorylation of the enzymes to initiate its activation process. We report other regulation mechanisms of CaM kinases, such as S-glutathionylation of CaM kinase I at Cys 179 and S-nitrosylation of CaM kinase II at Cys 6/30. Such unique post-translational modification of CaMKs by NO shed light on a new area of mutual regulation of NO- and CaM kinases-signals. Based on the novel direct regulation of these kinases, we propose that CaM kinases/NO signaling would be good targets for understanding how they can participate in neuronal physiology and disease.
KW - Calmodulin-dependent protein kinase
KW - Redox regulation
KW - S-Glutathionylation
KW - S-Nitrosylation
UR - http://www.scopus.com/inward/record.url?scp=80051549483&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051549483&partnerID=8YFLogxK
U2 - 10.1016/j.niox.2011.01.004
DO - 10.1016/j.niox.2011.01.004
M3 - Article
C2 - 21255668
AN - SCOPUS:80051549483
VL - 25
SP - 145
EP - 152
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
SN - 1089-8603
IS - 2
ER -