S-nitrosylation induces both autonomous activation and inhibition of calcium/calmodulin-dependent protein Kinase II δ

Jeffrey R. Erickson, C. Blake Nichols, Hitoshi Uchinoumi, Matthew L. Stein, Julie B C Bossuyt, Donald M Bers

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

NO is known to modulate calcium handling and cellular signaling in the myocardium, but key targets for NO in the heart remain unidentified. Recent reports have implied that NO can activate calcium/calmodulin (Ca2+/CaM)-dependent protein kinase II (CaMKII) in neurons and the heart. Here we use our novel sensor of CaMKII activation, Camui, to monitor changes in the conformation and activation of cardiac CaMKII (CaMKIIS) activity after treatment with the NO donor S-nitrosoglutathione (GSNO). We demonstrate that exposure to NO after Ca2+/CaM binding to CaMKIIS results in autonomous kinase activation, which is abolished by mutation of the Cys-290 site. However, exposure of CaMKIIS to GSNO prior to Ca2+/CaM exposure strongly suppresses kinase activation and conformational change by Ca2+/CaM. This NO-induced inhibition was ablated by mutation of the Cys-273 site. We found parallel effects of GSNO on CaM/CaMKIIS binding and CaMKIIS-de-pendent ryanodine receptor activation in adult cardiac myocytes. We conclude that NO can play a dual role in regulating cardiac CaMKIIS activity.

Original languageEnglish (US)
Pages (from-to)25646-25656
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number42
DOIs
StatePublished - Oct 16 2015

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Protein Kinases
Chemical activation
Phosphotransferases
S-Nitrosoglutathione
Calcium
Ryanodine Receptor Calcium Release Channel
Mutation
Calmodulin
Cardiac Myocytes
Myocardium
Cell signaling
Neurons
Conformations
Thermodynamic properties
Sensors

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

S-nitrosylation induces both autonomous activation and inhibition of calcium/calmodulin-dependent protein Kinase II δ. / Erickson, Jeffrey R.; Nichols, C. Blake; Uchinoumi, Hitoshi; Stein, Matthew L.; Bossuyt, Julie B C; Bers, Donald M.

In: Journal of Biological Chemistry, Vol. 290, No. 42, 16.10.2015, p. 25646-25656.

Research output: Contribution to journalArticle

Erickson, Jeffrey R. ; Nichols, C. Blake ; Uchinoumi, Hitoshi ; Stein, Matthew L. ; Bossuyt, Julie B C ; Bers, Donald M. / S-nitrosylation induces both autonomous activation and inhibition of calcium/calmodulin-dependent protein Kinase II δ. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 42. pp. 25646-25656.
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