Ser1176

Site Information
TSRIRtQsFsLQERQ SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447884

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 30 ) , immunoprecipitation ( 1 , 6 ) , mass spectrometry ( 2 , 3 , 4 , 5 , 9 , 12 , 14 , 19 , 20 , 22 , 23 , 24 , 26 ) , mutation of modification site ( 1 ) , phospho-antibody ( 1 , 7 , 8 , 10 , 11 , 15 , 16 , 17 , 18 , 21 , 25 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ) , western blotting ( 1 , 6 , 7 , 8 , 10 , 11 , 15 , 16 , 17 , 18 , 21 , 25 , 27 , 28 , 29 , 31 , 33 )
Disease tissue studied:	cervical cancer ( 21 ) , cervical adenocarcinoma ( 21 ) , lung cancer ( 21 )
Relevant cell line - cell type - tissue:	'3T3-L1, differentiated' (adipocyte) ( 2 , 4 ) , 'brain, embryonic' ( 22 , 23 ) , 'fat, brown' ( 9 ) , 'muscle, skeletal' ( 10 ) , 'stem, embryonic' ( 12 ) , A549 (pulmonary) ( 21 ) , aorta ( 7 , 15 , 18 , 25 , 27 , 29 ) , BAEC (endothelial) ( 21 , 30 ) , brain ( 24 ) , EC (endothelial) ( 33 ) , heart ( 5 , 9 , 16 , 17 , 20 ) , HeLa S3 (cervical) ( 21 ) , HUVEC (endothelial) ( 1 , 30 ) , kidney ( 9 ) , liver ( 3 , 9 , 19 , 26 ) , lung ( 9 ) , MEF (fibroblast) ( 11 ) , microvessel endothelial-lung ( 8 ) , myocardium ( 27 ) , myocyte-heart ( 30 ) , penis ( 32 ) , platelet-blood ( 15 ) , RAW 264.7 (macrophage) ( 6 ) , spleen ( 9 ) , thoracic aorta ( 21 , 28 , 31 ) , vascular smooth muscle cell ('muscle, smooth') ( 21 )

Upstream Regulation
Regulatory protein:	AMPKA2 (mouse) ( 11 , 16 ) , APOE (mouse) ( 7 ) , BVR (human) ( 6 ) , PKCA (mouse) ( 30 ) , PPP2CA (mouse) ( 21 )
Putative in vivo kinases:	CAMK2A (human) ( 6 ) , PKACA (human) ( 8 )
Treatments:	8-(3-chlorostyryl) caffeine ( 17 ) , acadesine ( 29 ) , ACh ( 7 ) , Akt_inhibitor_IV ( 8 ) , alloxazine ( 17 ) , angiotensin_2 ( 28 ) , atorvastatin ( 17 , 27 , 33 ) , BAPTA-AM ( 6 ) , blood pressure ( 28 ) , DPCPX ( 17 ) , FGF2 ( 30 ) , geldanamycin ( 33 ) , H-89 ( 28 ) , hypertension ( 31 ) , icatibant ( 28 , 31 ) , IL-6 ( 25 ) , insulin ( 4 , 25 ) , ischemia ( 10 ) , ischemia/reperfusion ( 16 ) , JNK_inhibitor_I ( 25 ) , KT5720 ( 28 ) , LY294002 ( 4 , 6 , 8 , 28 , 33 ) , metformin ( 16 , 29 ) , MK-2206 ( 4 ) , MK801 ( 8 ) , mPKI ( 8 ) , MRS-1523 ( 17 ) , nicardipine ( 31 ) , oleic_acid ( 21 ) , palmitate ( 21 ) , PD123319 ( 28 , 31 ) , PD98059 ( 6 , 25 ) , PGE2 ( 18 ) , SPT ( 17 ) , STO-609 ( 6 ) , Theophylline ( 17 ) , U0126 ( 17 ) , uPA ( 8 ) , VEGF ( 32 ) , wortmannin ( 28 )

Downstream Regulation
Effects of modification on eNOS:	enzymatic activity, induced ( 8 , 30 ) , molecular association, regulation ( 8 )
Effects of modification on biological processes:	signaling pathway regulation ( 6 )
Induce interaction with:	CTNNB1 (human) ( 8 )

References
1	Shang F, et al. (2016) Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade. PLoS One 11, e0151845 26986624 Curated Info
2	Parker BL, et al. (2015) Targeted phosphoproteomics of insulin signaling using data-independent acquisition mass spectrometry. Sci Signal 8, rs6 26060331 Curated Info
3	Wilson-Grady JT, Haas W, Gygi SP (2013) Quantitative comparison of the fasted and re-fed mouse liver phosphoproteomes using lower pH reductive dimethylation. Methods 61, 277-86 23567750 Curated Info
4	Humphrey SJ, et al. (2013) Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2. Cell Metab 17, 1009-20 23684622 Curated Info
5	Lundby A, et al. (2013) In vivo phosphoproteomics analysis reveals the cardiac targets of β-adrenergic receptor signaling. Sci Signal 6, rs11 23737553 Curated Info
6	Wegiel B, et al. (2011) Biliverdin inhibits Toll-like receptor-4 (TLR4) expression through nitric oxide-dependent nuclear translocation of biliverdin reductase. Proc Natl Acad Sci U S A 108, 18849-54 22042868 Curated Info
7	Capettini LS, et al. (2011) Decreased production of neuronal NOS-derived hydrogen peroxide contributes to endothelial dysfunction in atherosclerosis. Br J Pharmacol 164, 1738-48 21615722 Curated Info
8	Makarova AM, et al. (2011) Urokinase-type plasminogen activator (uPA) induces pulmonary microvascular endothelial permeability through low density lipoprotein receptor-related protein (LRP)-dependent activation of endothelial nitric-oxide synthase. J Biol Chem 286, 23044-53 21540184 Curated Info
9	Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89 21183079 Curated Info
10	Ohashi K, et al. (2010) LKB1 deficiency in Tie2-Cre-expressing cells impairs ischemia-induced angiogenesis. J Biol Chem 285, 22291-8 20489196 Curated Info
11	Chen Z, et al. (2010) Shear stress, SIRT1, and vascular homeostasis. Proc Natl Acad Sci U S A 107, 10268-73 20479254 Curated Info
12	Tucker M (2010) CST Curation Set: 9080; Year: 2010; Biosample/Treatment: cell line, embryonic stem cells (mouse)/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
13	Loot AE, Schreiber JG, Fisslthaler B, Fleming I (2009) Angiotensin II impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase. J Exp Med 206, 2889-96 19934023 Curated Info
14	Rikova K (2008) CST Curation Set: 5296; Year: 2008; Biosample/Treatment: cell line, Dana Farber-KTL(LN)-4/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Curated Info
15	Gambaryan S, et al. (2008) NO-synthase-/NO-independent regulation of human and murine platelet soluble guanylyl cyclase activity. J Thromb Haemost 6, 1376-84 18485089 Curated Info
16	Calvert JW, et al. (2008) Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling. Diabetes 57, 696-705 18083782 Curated Info
17	Merla R, et al. (2007) The central role of adenosine in statin-induced ERK1/2, Akt, and eNOS phosphorylation. Am J Physiol Heart Circ Physiol 293, H1918-28 17616749 Curated Info
18	Hristovska AM, et al. (2007) Prostaglandin E2 induces vascular relaxation by E-prostanoid 4 receptor-mediated activation of endothelial nitric oxide synthase. Hypertension 50, 525-30 17635857 Curated Info
19	Guo A (2007) CST Curation Set: 2920; Year: 2007; Biosample/Treatment: tissue, liver/-; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
20	Guo A (2007) CST Curation Set: 2922; Year: 2007; Biosample/Treatment: tissue, heart/-; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
21	Wu Y, et al. (2007) Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. J Biol Chem 282, 9777-88 17255104 Curated Info
22	Guo A (2007) CST Curation Set: 2672; Year: 2007; Biosample/Treatment: tissue, brain/-; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
23	Guo A (2007) CST Curation Set: 2677; Year: 2007; Biosample/Treatment: tissue, brain/-; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
24	Guo A (2007) CST Curation Set: 2682; Year: 2007; Biosample/Treatment: tissue, brain/-; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
25	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
26	Villén J, Beausoleil SA, Gerber SA, Gygi SP (2007) Large-scale phosphorylation analysis of mouse liver. Proc Natl Acad Sci U S A 104, 1488-93 17242355 Curated Info
27	Sun W, et al. (2006) Statins activate AMP-activated protein kinase in vitro and in vivo. Circulation 114, 2655-62 17116771 Curated Info
28	Yayama K, Hiyoshi H, Imazu D, Okamoto H (2006) Angiotensin II stimulates endothelial NO synthase phosphorylation in thoracic aorta of mice with abdominal aortic banding via type 2 receptor. Hypertension 48, 958-64 17000928 Curated Info
29	Davis BJ, Xie Z, Viollet B, Zou MH (2006) Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes 55, 496-505 16443786 Curated Info
30	Partovian C, et al. (2005) PKCalpha activates eNOS and increases arterial blood flow in vivo. Circ Res 97, 482-7 16081872 Curated Info
31	Hiyoshi H, Yayama K, Takano M, Okamoto H (2005) Angiotensin type 2 receptor-mediated phosphorylation of eNOS in the aortas of mice with 2-kidney, 1-clip hypertension. Hypertension 45, 967-73 15837834 Curated Info
32	Musicki B, Palese MA, Crone JK, Burnett AL (2004) Phosphorylated endothelial nitric oxide synthase mediates vascular endothelial growth factor-induced penile erection. Biol Reprod 70, 282-9 14522830 Curated Info
33	Brouet A, et al. (2001) Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins. Circ Res 89, 866-73 11701613 Curated Info