Thr495
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Home > Phosphorylation Site Page: > Thr495  -  eNOS (human)

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

In vivo Characterization
Methods used to characterize site in vivo:
mass spectrometry ( 1 , 4 ) , mutation of modification site ( 18 , 20 ) , phospho-antibody ( 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 23 ) , western blotting ( 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 16 , 17 , 18 , 23 )
Disease tissue studied:
breast cancer ( 1 ) , breast cancer, triple negative ( 1 ) , gastric cancer ( 4 ) , gastric carcinoma ( 4 )
Relevant cell line - cell type - tissue:
artery-heart ( 10 ) , BAEC (endothelial) ( 5 ) , breast ( 1 ) , CHO (fibroblast) [MAS1 (human)] ( 7 ) , COS (fibroblast) ( 15 , 18 , 20 ) , endothelial-aorta ( 18 ) , HAEC (endothelial) ( 7 , 12 , 17 , 23 ) , HUVEC (endothelial) ( 6 , 8 , 9 , 11 , 13 , 16 , 20 , 21 ) , HUVEC (endothelial) [IRS1 (human)] ( 16 ) , MKN-45 (gastric) ( 4 ) , PAE (endothelial) ( 14 , 20 )

Upstream Regulation
Regulatory protein:
AMPKA2 (human) ( 14 ) , IRS1 (human) ( 16 ) , PTEN (human) ( 23 )
Kinases, in vitro:
PKACA (human) ( 22 ) , PKCA (human) ( 5 ) , PKG2 (human) ( 22 )
Treatments:
8-Rp-cAMP ( 10 ) , A-779 ( 7 ) , A23187 ( 5 ) , aldosterone ( 9 ) , angiotensin-(1-7) ( 7 ) , bradykinin ( 20 ) , Ca(2+) ( 20 ) , calyculin_A ( 6 , 10 , 20 ) , ciclosporin ( 20 ) , colforsin ( 10 ) , compound_C ( 14 ) , eplerenone ( 9 ) , estradiol ( 14 ) , glucose ( 17 ) , HDL ( 18 ) , histamine ( 20 ) , hydroxyurea ( 8 ) , IL-6 ( 6 ) , insulin ( 6 , 16 ) , JNK_inhibitor_I ( 6 ) , LY294002 ( 6 , 10 ) , okadaic_acid ( 9 , 20 ) , Ox-PAPC ( 12 ) , PAF ( 3 ) , PAR1-activating_peptide ( 13 ) , PD98059 ( 6 ) , phorbol_ester ( 5 , 20 ) , Ro31-8220 ( 21 ) , rosiglitazone ( 11 ) , serum ( 13 ) , thrombin ( 13 ) , VEGF ( 5 , 9 , 21 ) , wortmannin ( 20 )

Downstream Regulation
Effects of modification on eNOS:
enzymatic activity, inhibited ( 20 ) , molecular association, regulation ( 19 , 20 )
Inhibit interaction with:
Calmodulin (human) ( 19 , 20 )

References 

1

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

2

Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21
23312004   Curated Info

3

Sánchez FA, et al. (2011) Functional significance of cytosolic endothelial nitric-oxide synthase (eNOS): regulation of hyperpermeability. J Biol Chem 286, 30409-14
21757745   Curated Info

4

Moritz A (2011) CST Curation Set: 12383; Year: 2011; Biosample/Treatment: cell line, MKN-45/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P , PTMScan(R) PLK Binding Motif (SpTP) Immunoaffinity Beads Cat#: 1995
Curated Info

5

Chen CA, et al. (2008) Phosphorylation of endothelial nitric-oxide synthase regulates superoxide generation from the enzyme. J Biol Chem 283, 27038-47
18622039   Curated Info

6

Andreozzi F, et al. (2007) Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells. Mol Cell Biol 27, 2372-83
17242212   Curated Info

7

Sampaio WO, et al. (2007) Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways. Hypertension 49, 185-92
17116756   Curated Info

8

Cokic VP, et al. (2006) Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells. Blood 108, 184-91
16527893   Curated Info

9

Nagata D, et al. (2006) Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity. Hypertension 48, 165-71
16754797   Curated Info

10

Zhang XP, Hintze TH (2006) cAMP signal transduction induces eNOS activation by promoting PKB phosphorylation. Am J Physiol Heart Circ Physiol 290, H2376-84
16428343   Curated Info

11

Kim KY, Cheon HG (2006) Antiangiogenic effect of rosiglitazone is mediated via peroxisome proliferator-activated receptor gamma-activated maxi-K channel opening in human umbilical vein endothelial cells. J Biol Chem 281, 13503-12
16527820   Curated Info

12

Gharavi NM, et al. (2006) Role of endothelial nitric oxide synthase in the regulation of SREBP activation by oxidized phospholipids. Circ Res 98, 768-76
16497987   Curated Info

13

David-Dufilho M, et al. (2005) Endothelial thrombomodulin induces Ca2+ signals and nitric oxide synthesis through epidermal growth factor receptor kinase and calmodulin kinase II. J Biol Chem 280, 35999-6006
16126727   Curated Info

14

Schulz E, Anter E, Zou MH, Keaney JF (2005) Estradiol-mediated endothelial nitric oxide synthase association with heat shock protein 90 requires adenosine monophosphate-dependent protein kinase. Circulation 111, 3473-80
15967841   Curated Info

15

Fulton D, et al. (2004) Targeting of endothelial nitric-oxide synthase to the cytoplasmic face of the Golgi complex or plasma membrane regulates Akt- versus calcium-dependent mechanisms for nitric oxide release. J Biol Chem 279, 30349-57
15136572   Curated Info

16

Federici M, et al. (2004) G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide synthase in cultured human endothelial cells. Circulation 109, 399-405
14707024   Curated Info

17

Salt IP, et al. (2003) High glucose inhibits insulin-stimulated nitric oxide production without reducing endothelial nitric-oxide synthase Ser1177 phosphorylation in human aortic endothelial cells. J Biol Chem 278, 18791-7
12644458   Curated Info

18

Mineo C, Yuhanna IS, Quon MJ, Shaul PW (2003) High density lipoprotein-induced endothelial nitric-oxide synthase activation is mediated by Akt and MAP kinases. J Biol Chem 278, 9142-9
12511559   Curated Info

19

Aoyagi M, Arvai AS, Tainer JA, Getzoff ED (2003) Structural basis for endothelial nitric oxide synthase binding to calmodulin. EMBO J 22, 766-75
12574113   Curated Info

20

Fleming I, et al. (2001) Phosphorylation of Thr(495) regulates Ca(2+)/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res 88, E68-75
11397791   Curated Info

21

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

22

Butt E, et al. (2000) Endothelial nitric-oxide synthase (type III) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases. J Biol Chem 275, 5179-87
10671564   Curated Info

23

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