Ser473

Site Information
RPHFPQFsYSASATA SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447855

In vivo Characterization
Methods used to characterize site in vivo:	mutation of modification site ( 5 , 8 , 18 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 )
Relevant cell line - cell type - tissue:	'granulosa, luteal' ( 4 ) , BAEC (endothelial) ( 1 , 2 , 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 18 , 19 ) , BAE ( 13 ) , chromaffin-adrenal gland ( 17 ) , COS (fibroblast) ( 8 ) , endothelial-aorta ( 15 , 20 ) , HAEC (endothelial) ( 10 ) , HUVEC (endothelial) ( 8 ) , MEF (fibroblast) ( 18 ) , VSMC-aorta ( 16 )

Upstream Regulation
Regulatory protein:	5-HT(2A) (human) ( 16 ) , AMPKA1 (human) ( 9 ) , DHFRL1 (human) ( 6 ) , DYN1 (human) ( 8 ) , GCH1 (human) ( 6 ) , HRas (human) ( 11 ) , HSP90A (human) ( 18 ) , IRS1 (rat) ( 2 ) , IRS2 (human) ( 2 ) , IRS2 (rat) ( 2 ) , PIK3CA (human) ( 2 ) , PIK3R1 (cow) ( 2 ) , PKACA (cow) ( 7 ) , RAC1 (human) ( 7 , 15 )
Treatments:	20-HETE ( 12 ) , 5-HT ( 16 ) , 7,8-dihydrobiopterin ( 6 ) , angiopoietin-1 ( 1 , 5 ) , angiotensin ( 2 ) , AP21967 ( 21 ) , aPL ( 3 ) , cAMP_analog ( 19 ) , compound_C ( 9 ) , dinoprost ( 4 ) , fluid_shear_stress ( 19 ) , GF109203X ( 2 ) , ghrelin ( 10 ) , H2O2 ( 11 , 18 ) , IGF-1 ( 4 ) , IgG ( 3 ) , insulin ( 2 , 10 , 11 , 14 ) , laminar flow ( 9 ) , LDL_oxidized ( 11 ) , LY294002 ( 16 , 21 ) , nicotine ( 17 ) , ONOO(-) ( 11 ) , oscillatory_flow ( 9 ) , PD98059 ( 10 , 11 , 14 ) , phorbol_ester ( 2 ) , PP2 ( 7 , 15 ) , prasterone ( 14 ) , PTX ( 15 ) , quercetin ( 13 ) , racepinefrine ( 7 ) , rapamycin ( 4 ) , sapropterin ( 6 ) , siRNA ( 15 ) , sphingosine_1-phosphate ( 15 , 20 ) , staurosporine ( 21 ) , U0126 ( 4 , 7 , 11 ) , VEGF ( 1 , 2 , 3 , 5 , 6 , 8 , 11 , 12 , 19 , 20 ) , wortmannin ( 4 , 7 , 9 , 10 , 14 , 15 , 16 , 20 )

Upstream Regulation

Regulatory protein:

5-HT(2A) (human) ( 16 ) , AMPKA1 (human) ( 9 ) , DHFRL1 (human) ( 6 ) , DYN1 (human) ( 8 ) , GCH1 (human) ( 6 ) , HRas (human) ( 11 ) , HSP90A (human) ( 18 ) , IRS1 (rat) ( 2 ) , IRS2 (human) ( 2 ) , IRS2 (rat) ( 2 ) , PIK3CA (human) ( 2 ) , PIK3R1 (cow) ( 2 ) , PKACA (cow) ( 7 ) , RAC1 (human) ( 7 , 15 )

Treatments:

20-HETE ( 12 ) , 5-HT ( 16 ) , 7,8-dihydrobiopterin ( 6 ) , angiopoietin-1 ( 1 , 5 ) , angiotensin ( 2 ) , AP21967 ( 21 ) , aPL ( 3 ) , cAMP_analog ( 19 ) , compound_C ( 9 ) , dinoprost ( 4 ) , fluid_shear_stress ( 19 ) , GF109203X ( 2 ) , ghrelin ( 10 ) , H2O2 ( 11 , 18 ) , IGF-1 ( 4 ) , IgG ( 3 ) , insulin ( 2 , 10 , 11 , 14 ) , laminar flow ( 9 ) , LDL_oxidized ( 11 ) , LY294002 ( 16 , 21 ) , nicotine ( 17 ) , ONOO(-) ( 11 ) , oscillatory_flow ( 9 ) , PD98059 ( 10 , 11 , 14 ) , phorbol_ester ( 2 ) , PP2 ( 7 , 15 ) , prasterone ( 14 ) , PTX ( 15 ) , quercetin ( 13 ) , racepinefrine ( 7 ) , rapamycin ( 4 ) , sapropterin ( 6 ) , siRNA ( 15 ) , sphingosine_1-phosphate ( 15 , 20 ) , staurosporine ( 21 ) , U0126 ( 4 , 7 , 11 ) , VEGF ( 1 , 2 , 3 , 5 , 6 , 8 , 11 , 12 , 19 , 20 ) , wortmannin ( 4 , 7 , 9 , 10 , 14 , 15 , 16 , 20 )

Downstream Regulation
Effects of modification on Akt1:	activity, induced ( 16 ) , enzymatic activity, induced ( 21 ) , intracellular localization ( 21 )
Effects of modification on biological processes:	cell growth, altered ( 16 )

References
1	Chidiac R, et al. (2016) Comparative Phosphoproteomics Analysis of VEGF and Angiopoietin-1 Signaling Reveals ZO-1 as a Critical Regulator of Endothelial Cell Proliferation. Mol Cell Proteomics 15, 1511-25 26846344 Curated Info
2	Maeno Y, et al. (2012) Inhibition of Insulin Signaling in Endothelial Cells by Protein Kinase C-induced Phosphorylation of p85 Subunit of Phosphatidylinositol 3-Kinase (PI3K). J Biol Chem 287, 4518-30 22158866 Curated Info
3	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
4	Arvisais E, et al. (2010) Prostaglandin F2alpha represses IGF-I-stimulated IRS1/phosphatidylinositol-3-kinase/AKT signaling in the corpus luteum: role of ERK and P70 ribosomal S6 kinase. Mol Endocrinol 24, 632-43 20160123 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	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
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	Duval M, Le Boeuf F, Huot J, Gratton JP (2007) Src-mediated phosphorylation of Hsp90 in response to vascular endothelial growth factor (VEGF) is required for VEGF receptor-2 signaling to endothelial NO synthase. Mol Biol Cell 18, 4659-68 17855507 Curated Info
9	Guo D, Chien S, Shyy JY (2007) Regulation of endothelial cell cycle by laminar versus oscillatory flow: distinct modes of interactions of AMP-activated protein kinase and Akt pathways. Circ Res 100, 564-71 17272808 Curated Info
10	Iantorno M, et al. (2007) Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells. Am J Physiol Endocrinol Metab 292, E756-64 17106060 Curated Info
11	Clavreul N, et al. (2006) S-glutathiolation of p21ras by peroxynitrite mediates endothelial insulin resistance caused by oxidized low-density lipoprotein. Arterioscler Thromb Vasc Biol 26, 2454-61 16931794 Curated Info
12	Chen Y, et al. (2006) Mechanisms of activation of eNOS by 20-HETE and VEGF in bovine pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 291, L378-85 16679377 Curated Info
13	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
14	Formoso G, et al. (2006) Dehydroepiandrosterone mimics acute actions of insulin to stimulate production of both nitric oxide and endothelin 1 via distinct phosphatidylinositol 3-kinase- and mitogen-activated protein kinase-dependent pathways in vascular endothelium. Mol Endocrinol 20, 1153-63 16373398 Curated Info
15	Gonzalez E, Kou R, Michel T (2006) Rac1 modulates sphingosine 1-phosphate-mediated activation of phosphoinositide 3-kinase/Akt signaling pathways in vascular endothelial cells. J Biol Chem 281, 3210-6 16339142 Curated Info
16	Liu Y, Fanburg BL (2006) Serotonin-induced growth of pulmonary artery smooth muscle requires activation of phosphatidylinositol 3-kinase/serine-threonine protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase 1. Am J Respir Cell Mol Biol 34, 182-91 16195541 Curated Info
17	Evans GJ, et al. (2006) Protein kinase B/Akt is a novel cysteine string protein kinase that regulates exocytosis release kinetics and quantal size. J Biol Chem 281, 1564-72 16243840 Curated Info
18	Zhang R, et al. (2005) Hsp90-Akt phosphorylates ASK1 and inhibits ASK1-mediated apoptosis. Oncogene 24, 3954-63 15782121 Curated Info
19	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
20	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
21	Scheid MP, Marignani PA, Woodgett JR (2002) Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B. Mol Cell Biol 22, 6247-60 12167717 Curated Info