Ser116
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Home > Phosphorylation Site Page: > Ser116  -  eNOS (cow)

Site Information
RKLQTRPsPGPPPAE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448638

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 15 ) , [32P] bio-synthetic labeling ( 11 , 15 ) , mass spectrometry ( 15 ) , mutation of modification site ( 6 , 10 , 11 , 14 ) , peptide sequencing ( 15 ) , phospho-antibody ( 1 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 16 ) , phosphoamino acid analysis ( 15 ) , phosphopeptide mapping ( 15 ) , western blotting ( 1 , 3 , 4 , 5 , 6 , 8 , 9 , 11 , 12 , 13 , 14 , 16 )
Relevant cell line - cell type - tissue:
BAEC (endothelial) ( 1 , 3 , 4 , 6 , 9 , 10 , 11 , 12 ) , BAE ( 5 ) , BLMVEC (endothelial) ( 8 ) , COS (fibroblast) ( 6 , 10 , 11 , 14 , 16 ) , endothelial-aorta ( 7 , 13 , 15 )

Upstream Regulation
Regulatory protein:
DHFRL1 (human) ( 3 ) , eNOS (cow) ( 6 ) , GCH1 (human) ( 3 ) , PPP2R5D (rat) ( 1 ) , PTEN (human) ( 16 ) , RAC1 (human) ( 4 )
Putative in vivo kinases:
ERK2 (human) ( 2 )
Phosphatases, in vitro:
PPP2CA (human) ( 11 )
Treatments:
7,8-dihydrobiopterin ( 3 ) , aphidicolin ( 1 ) , apoA-I ( 7 ) , atenolol ( 4 ) , ATP ( 10 ) , butoxamine ( 4 ) , calphostin_C ( 14 ) , calyculin_A ( 11 ) , cAMP_analog ( 12 ) , ciclosporin ( 11 , 14 ) , fluid_shear_stress ( 12 , 15 ) , HDL ( 7 ) , high_cell_density ( 12 ) , LDL ( 7 ) , okadaic_acid ( 11 ) , PP2 ( 4 ) , quercetin ( 5 ) , racepinefrine ( 4 ) , sapropterin ( 3 ) , SR59230A ( 4 ) , troglitazone ( 9 ) , U0126 ( 4 ) , vanadate ( 8 ) , VEGF ( 3 , 10 , 11 , 12 , 14 ) , wortmannin ( 4 )

Downstream Regulation
Effects of modification on eNOS:
enzymatic activity, inhibited ( 10 , 14 ) , molecular association, regulation ( 10 ) , phosphorylation ( 10 )
Inhibit interaction with:
Akt1 (human) ( 10 )

References 

1

Park JH, et al. (2015) B56δ subunit of protein phosphatase 2A decreases phosphorylation of endothelial nitric oxide synthase at serine 116: Mechanism underlying aphidicolin-stimulated NO production. Nitric Oxide 50, 46-51
26255574   Curated Info

2

Ruan L, et al. (2013) Calcineurin-mediated dephosphorylation of eNOS at serine 116 affects eNOS enzymatic activity indirectly by facilitating c-Src binding and tyrosine 83 phosphorylation. Vascul Pharmacol 59, 27-35
23727078   Curated Info

3

Sugiyama T, Levy BD, Michel T (2009) Tetrahydrobiopterin recycling, a key determinant of endothelial nitric-oxide synthase-dependent signaling pathways in cultured vascular endothelial cells. J Biol Chem 284, 12691-700
19286667   Curated Info

4

Kou R, Michel T (2007) Epinephrine regulation of the endothelial nitric-oxide synthase: roles of RAC1 and beta3-adrenergic receptors in endothelial NO signaling. J Biol Chem 282, 32719-29
17855349   Curated Info

5

Jackson SJ, Venema RC (2006) Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells. J Nutr 136, 1178-84
16614401   Curated Info

6

Church JE, Fulton D (2006) Differences in eNOS activity because of subcellular localization are dictated by phosphorylation state rather than the local calcium environment. J Biol Chem 281, 1477-88
16257964   Curated Info

7

Drew BG, et al. (2004) High-density lipoprotein and apolipoprotein AI increase endothelial NO synthase activity by protein association and multisite phosphorylation. Proc Natl Acad Sci U S A 101, 6999-7004
15107497   Curated Info

8

Papapetropoulos A, et al. (2004) Vanadate is a potent activator of endothelial nitric-oxide synthase: evidence for the role of the serine/threonine kinase Akt and the 90-kDa heat shock protein. Mol Pharmacol 65, 407-15
14742683   Curated Info

9

Cho DH, Choi YJ, Jo SA, Jo I (2004) Nitric oxide production and regulation of endothelial nitric-oxide synthase phosphorylation by prolonged treatment with troglitazone: evidence for involvement of peroxisome proliferator-activated receptor (PPAR) gamma-dependent and PPARgamma-independent signaling pathways. J Biol Chem 279, 2499-506
14593122   Curated Info

10

Bauer PM, et al. (2003) Compensatory phosphorylation and protein-protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric-oxide synthase. J Biol Chem 278, 14841-9
12591925   Curated Info

11

Greif DM, Kou R, Michel T (2002) Site-specific dephosphorylation of endothelial nitric oxide synthase by protein phosphatase 2A: evidence for crosstalk between phosphorylation sites. Biochemistry 41, 15845-53
12501214   Curated Info

12

Boo YC, et al. (2002) Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism. Am J Physiol Heart Circ Physiol 283, H1819-28
12384459   Curated Info

13

Gonzalez E, et al. (2002) Subcellular targeting and agonist-induced site-specific phosphorylation of endothelial nitric-oxide synthase. J Biol Chem 277, 39554-60
12189156   Curated Info

14

Kou R, Greif D, Michel T (2002) Dephosphorylation of endothelial nitric-oxide synthase by vascular endothelial growth factor. Implications for the vascular responses to cyclosporin A. J Biol Chem 277, 29669-73
12050171   Curated Info

15

Gallis B, et al. (1999) Identification of flow-dependent endothelial nitric-oxide synthase phosphorylation sites by mass spectrometry and regulation of phosphorylation and nitric oxide production by the phosphatidylinositol 3-kinase inhibitor LY294002. J Biol Chem 274, 30101-8
10514497   Curated Info

16

Church JE, et al. Inhibition of endothelial nitric oxide synthase by the lipid phosphatase PTEN. Vascul Pharmacol 52, 191-8
19962452   Curated Info