+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Nitric oxide synthase regulatory sites phosphorylation by cyclic amp dependent protein kinase protein kinase c and calcium calmodulin protein kinase identification of flavin and calmodulin binding sites



Nitric oxide synthase regulatory sites phosphorylation by cyclic amp dependent protein kinase protein kinase c and calcium calmodulin protein kinase identification of flavin and calmodulin binding sites



Journal of Biological Chemistry 267(16): 10976-10981



Nitric oxide (NO) is an important molecular messenger accounting for endothelial-derived relaxing activity in blood vessels, mediating cytotoxic actions of macrophages, and function as a neurotransmitter in the brain and periphery. NO synthase (NOS) from brain has been purified to homogeneity and molecularly cloned. We now report that NOS is stoichiometrically phosphorylated by cAMP dependent protein kinase, protein kinase C, and calcium/calmodulin-dependent protein kinase, with each kinase phosphorylating a different serine site on NOS. Activation of PKC in transfected cells reduces NOS enzyme activity by .apprxeq. 77% in intact cells and by 50% in protein homogenates from these cells. Utilizing fluorescence spectroscopy we find that purified monomer NOS contains 1 molar equivalent of both FMN and FAD. This stoichiometry is supported by enzymatic digestion of the flavins with phosphodiesterase, and titration of the FMN with a specific FMN binding protein. We demonstrate that purified NOS is labeled by a photoaffinity derivative of calmodulin. These recognition sites on NOS provide multiple means or regulation of NO levels and "cross-talk" between second messenger systems.

(PDF emailed within 1 workday: $29.90)

Accession: 007595776

Download citation: RISBibTeXText

PMID: 1375933


Related references

Phosphorylation by calcium calmodulin-dependent protein kinase II and protein kinase C modulates the activity of nitric oxide synthase. Biochemical and Biophysical Research Communications 180(3): 1396-1402, 1991

Calcium calmodulin independent autophosphorylation sites of calcium calmodulin dependent protein kinase ii studies on the effect of phosphorylation of threonine 305 306 and serine 314 on calmodulin binding using synthetic peptides. Journal of Biological Chemistry 265(19): 11213-11219, 1990

Phosphorylation of P1, a high mobility group-like protein, catalyzed by casein kinase II, protein kinase C, cyclic AMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II. Febs Letters 258(1): 106-108, 1989

Effect of nitric oxide synthase inhibition on nuclear Ca++/calmodulin-dependent protein kinase IV kinase and nuclear Ca++/calmodulin-dependent protein kinase IV activity during hypoxia in neuronal nuclei of newborn piglets. Pediatric Research 53(4 Part 2): 552A, 2003

Identification of phosphorylation sites on glial fibrillary acidic protein for cdc2 kinase and Ca(2+)-calmodulin-dependent protein kinase II. Journal of Biochemistry 116(2): 426-434, 1994

Regulation of calcineurin by phosphorylation identification of the regulatory site phosphorylated by calcium calmodulin dependent protein kinase ii and protein kinase c. Journal of Biological Chemistry 264(28): 16524-16529, 1989

Extracellular Protein Kinase A Modulates Intracellular Calcium/Calmodulin-Dependent Protein Kinase II, Nitric Oxide Synthase, and the Glutamate-Nitric Oxide-cGMP Pathway in Cerebellum. Differential Effects in Hyperammonemia. Acs Chemical Neuroscience 7(12): 1753-1759, 2016

Phosphorylation of connexin 32 a hepatocyte gap junction protein by cyclic amp dependent protein kinase protein kinase c and calcium ion calmodulin dependent protein kinase ii. European Journal of Biochemistry 192(2): 263-274, 1990

Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase. Embo Journal 14(15): 3679-3686, 1995

Human calcium-calmodulin dependent protein kinase I: cDna cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase. The Embo Journal 14(15): 3679-3686, 1995

Emodin alleviates hepatic steatosis by inhibiting sterol regulatory element binding protein 1 activity by way of the calcium/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mechanistic target of rapamycin-p70 ribosomal S6 kinase signaling pathway. Hepatology Research 47(7): 683-701, 2016

Characterization of the sites phosphorylated on tyrosine hydroxylase by Ca2+ and phospholipid-dependent protein kinase, calmodulin-dependent multiprotein kinase and cyclic AMP-dependent protein kinase. Febs Letters 182(2): 335-339, 1985

Phosphorylation of liver pyruvate kinase by calcium calmodulin dependent protein kinase characterization of two phosphorylation sites. Biochemical & Biophysical Research Communications 139(3): 1017-1023, 1986

Phosphorylation of smooth muscle myosin light chain kinase by calcium ion calmodulin dependent protein kinase ii comparative study of the phosphorylation sites. Archives of Biochemistry & Biophysics 278(1): 41-45, 1990

Interactions of the autophosphorylation sites of calcium calmodulin dependent protein kinase ii with the calmodulin binding domain. FASEB Journal 2(5): ABSTRACT 4048, 1988