Thr497
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Home > Phosphorylation Site Page: > Thr497  -  eNOS (cow)

Site Information
AGITRKktFKEVANA   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447885

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 19 ) , immunoprecipitation ( 1 ) , mutation of modification site ( 5 , 8 , 11 , 17 , 19 , 22 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ) , phosphopeptide mapping ( 23 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 15 , 16 , 18 , 19 , 20 , 21 , 24 , 25 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 6 , 9 , 13 , 17 ) , BAE ( 10 , 22 ) , BAEC (endothelial) ( 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 11 , 12 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 ) , BLMVEC (endothelial) ( 15 ) , COS (fibroblast) ( 11 , 17 , 19 , 22 , 25 ) , endothelial-aorta ( 13 , 14 ) , PPAEC (endothelial) ( 1 ) , vascular smooth muscle cell ('muscle, smooth') [eNOS (cow)] ( 8 )

Upstream Regulation
Regulatory protein:
eNOS (cow) ( 11 ) , PKCZ (human) ( 5 ) , PTEN (human) ( 25 ) , RAC1 (human) ( 7 ) , TIE2 (human) ( 5 )
Putative in vivo kinases:
PKCA (cow) ( 18 ) , PKCZ (human) ( 5 )
Kinases, in vitro:
PKCA (human) ( 18 )
Phosphatases, in vitro:
PPP1CA (human) ( 23 ) , PPP2CA (human) ( 19 )
Treatments:
17-beta-estradiol ( 1 ) , A23187 ( 3 ) , angiopoietin-1 ( 5 ) , angiotensin_2 ( 8 ) , aphidicolin ( 2 ) , aPL ( 4 ) , apoA-I ( 14 ) , atenolol ( 7 ) , BAPTA-AM ( 3 ) , bisindolylmaleimide ( 3 , 5 ) , bradykinin ( 12 , 24 ) , butoxamine ( 7 ) , calyculin_A ( 23 ) , cAMP_analog ( 20 ) , ciclosporin ( 21 , 24 ) , colforsin ( 23 ) , fluid_shear_stress ( 20 ) , geldanamycin ( 13 ) , Go_6976 ( 5 ) , H2O2 ( 6 ) , HDL ( 14 ) , IBMX ( 23 ) , IgG ( 4 ) , insulin ( 3 ) , ionomycin ( 11 , 17 ) , lactacystin ( 9 ) , LDL ( 14 ) , MG132 ( 9 ) , nebivolol ( 12 ) , okadaic_acid ( 23 , 24 ) , phorbol_ester ( 5 , 17 , 18 , 23 ) , PP2 ( 7 ) , quercetin ( 10 ) , racepinefrine ( 7 ) , radicicol ( 13 ) , rottlerin ( 3 ) , SR59230A ( 7 ) , staurosporine ( 18 ) , thapsigargin ( 3 ) , troglitazone ( 16 ) , U0126 ( 7 ) , vanadate ( 15 ) , VEGF ( 3 , 4 , 5 , 17 , 20 , 21 , 22 , 24 ) , wortmannin ( 7 , 24 )

Downstream Regulation
Effects of modification on eNOS:
enzymatic activity, inhibited ( 17 , 18 , 23 ) , molecular association, regulation ( 1 )
Induce interaction with:
Calmodulin (cow) ( 1 )

References 

1

Tran QK, et al. (2016) Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1. J Biol Chem 291, 10805-23
26987903   Curated Info

2

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

3

Haines RJ, Corbin KD, Pendleton LC, Eichler DC (2012) Protein Kinase Cα Phosphorylates a Novel Argininosuccinate Synthase Site at Serine 328 during Calcium-dependent Stimulation of Endothelial Nitric-oxide Synthase in Vascular Endothelial Cells. J Biol Chem 287, 26168-76
22696221   Curated Info

4

Ramesh S, et al. (2011) Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via β2GPI and apoER2. J Clin Invest 121, 120-31
21123944   Curated Info

5

Oubaha M, Gratton JP (2009) Phosphorylation of endothelial nitric oxide synthase by atypical PKC zeta contributes to angiopoietin-1-dependent inhibition of VEGF-induced endothelial permeability in vitro. Blood 114, 3343-51
19564638   Curated Info

6

Hu Z, Chen J, Wei Q, Xia Y (2008) Bidirectional actions of hydrogen peroxide on endothelial nitric-oxide synthase phosphorylation and function: co-commitment and interplay of Akt and AMPK. J Biol Chem 283, 25256-63
18617528   Curated Info

7

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

8

Suzuki H, et al. (2006) Activation of endothelial nitric oxide synthase by the angiotensin II type 1 receptor. Endocrinology 147, 5914-20
16980435   Curated Info

9

Wei Q, Xia Y (2006) Proteasome inhibition down-regulates endothelial nitric-oxide synthase phosphorylation and function. J Biol Chem 281, 21652-9
16737962   Curated Info

10

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

11

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

12

Dessy C, et al. (2005) Endothelial beta3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary microvessels in response to the third-generation beta-blocker nebivolol. Circulation 112, 1198-205
16116070   Curated Info

13

Wei Q, Xia Y (2005) Roles of 3-phosphoinositide-dependent kinase 1 in the regulation of endothelial nitric-oxide synthase phosphorylation and function by heat shock protein 90. J Biol Chem 280, 18081-6
15737995   Curated Info

14

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

15

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

16

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

17

Lin MI, et al. (2003) Phosphorylation of threonine 497 in endothelial nitric-oxide synthase coordinates the coupling of L-arginine metabolism to efficient nitric oxide production. J Biol Chem 278, 44719-26
12952971   Curated Info

18

Matsubara M, Hayashi N, Jing T, Titani K (2003) Regulation of endothelial nitric oxide synthase by protein kinase C. J Biochem (Tokyo) 133, 773-81
12869534   Curated Info

19

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

20

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

21

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

22

Fulton D, et al. (2002) Localization of endothelial nitric-oxide synthase phosphorylated on serine 1179 and nitric oxide in Golgi and plasma membrane defines the existence of two pools of active enzyme. J Biol Chem 277, 4277-84
11729179   Curated Info

23

Michell BJ, et al. (2001) Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 276, 17625-8
11292821   Curated Info

24

Harris MB, et al. (2001) Reciprocal phosphorylation and regulation of endothelial nitric-oxide synthase in response to bradykinin stimulation. J Biol Chem 276, 16587-91
11340086   Curated Info

25

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