Calcium/calmodulin-dependent protein kinase I inhibits neuronal nitric-oxide synthase activity through serine 741 phosphorylation

FEBS Letters
Tao SongYasuo Watanabe

Abstract

We demonstrate here that neuronal nitric-oxide synthase (nNOS) is phosphorylated and inhibited by a constitutively active form of Ca2+/calmodulin (CaM)-dependent protein kinase I (CaM-K I1-293). Substitution of Ser741 to Ala in nNOS blocked the phosphorylation and the inhibitory effect. Mimicking phosphorylation at Ser741 by Ser to Asp mutation resulted in decreased binding of and activation by CaM, since the mutation was within the CaM-binding domain. CaM-K I1-293 gave phosphorylation of nNOS at Ser741 in transfected cells, resulting in 60-70% inhibition of nNOS activity. Wild-type CaM-K I also did phosphorylate nNOS at Ser741 in transfected cells, but either CaM-K II or CaM-K IV did not. These results raise the possibility of a novel cross-talk between nNOS and CaM-K I through the phosphorylation of Ser741 on nNOS.

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Citations

Jun 1, 2011·Journal of Ocular Biology, Diseases, and Informatics·Jan J BlomWilliam D Eldred
Jan 29, 2011·Neuroscience Bulletin·Chun-Xia Luo, Dong-Ya Zhu
Jan 25, 2011·Nitric Oxide : Biology and Chemistry·Tsuyoshi TakataYasuo Watanabe
Mar 21, 2009·Nitric Oxide : Biology and Chemistry·Li Zhou, Dong-Ya Zhu
Feb 10, 2009·Journal of Neurochemistry·Noriko MaedaHideyuki Yamamoto
Jul 1, 2008·The European Journal of Neuroscience·John Garthwaite
Aug 29, 2006·Nitric Oxide : Biology and Chemistry·Ramkumar KavyaMadhu Dikshit
Oct 8, 2013·Nitric Oxide : Biology and Chemistry·Jing LeiTimothy R Billiar
Sep 27, 2008·Neuron·Gary A WaymanThomas R Soderling
Jun 18, 2016·Frontiers in Physiology·Eduardo D CostaVirginia S Lemos
Sep 8, 2010·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Joern R SteinertIan D Forsythe
Mar 9, 2005·Hypertension·Marcela Herrera, Jeffrey L Garvin
May 29, 2020·Antioxidants & Redox Signaling·Tsuyoshi TakataYasuo Watanabe
Feb 15, 2008·The Biochemical Journal·Tao SongYasuo Watanabe
Sep 21, 2006·The Biochemical Journal·Tao SongYasuo Watanabe
May 18, 2016·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Yasuo Watanabe
Nov 25, 2020·International Journal of Molecular Sciences·Tsuyoshi TakataYasuo Watanabe
Oct 31, 2020·International Journal of Molecular Sciences·Shoma ArakiYasuo Watanabe

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