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AKT phosphorylates NOS3. 396 / 401
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sparser
"Since eNOS phosphorylation by AKT could be direct or indirect, eNOS inhibitor (1 mM N G -Monomethyl arginine, CalBiochem) was also used in this experiment as a control to test actual eNOS dependency (Figure xref )."

sparser
"Previously studies have demonstrated that Akt directly phosphorylates and activates eNOS in endothelial cells xref ."

reach
"Since eNOS phosphorylation by AKT could be direct or indirect, eNOS inhibitor (1 mM N G -Monomethyl arginine, CalBiochem) was also used in this experiment as a control to test actual eNOS dependency."

sparser
"NO release occurs via PI3K-Akt dependent phosphorylation of eNOS with Src-kinase playing a proximal role in these changes."

reach
"LA induced eNOS phosphorylation is mediated by PI 3 -kinase and Akt pathway."

sparser
"In addition, activation of Akt upregulated eNOS phosphorylation reduced ischemic oxidative stress."

reach
"The inability of VEGFR2 neutralization to affect flow induced Akt phosphorylation despite attenuating eNOS phosphorylation is consistent with the findings by Jo and colleagues, who demonstrated that shear stress stimulates phosphorylation of eNOS by an Akt independent mechanism [XREF_BIBR]."

reach
"Because Akt and eNOS are both localized in the bladder urothelium, phosphorylation of eNOS by Akt provides an attractive mechanism for rapid increases in urinary NO production."

sparser
"Akt can also phosphorylate and activate eNOS, leading to enhanced NO production and vasodilation ( xref ; xref )."

sparser
"Su and colleagues demonstrated that EPO is able to activate eNOS in endothelial cells by interacting with the βcR and causing Akt-dependent phosphorylation of eNOS ( xref )."

sparser
"Furthermore, eNOS-CaM undergoes phosphorylation by AKT, which leads to further NO production at the longer timescale, and is also thought to be calcium-independent."

sparser
"Decreased expression of endothelial NO synthase (eNOS) protein, decreased phosphorylation of eNOS by the serine-threonine kinase AKT, the presence of inhibitory substances (e.g., asymmetric dimethylarginine, ADMA), and hyporesponsiveness to NO underlie this endothelial dysfunction [ xref – xref ]."

reach
"Akt knockdown had no significant effect on CTRP9 induced AMPK phosphorylation, but blocked eNOS phosphorylation and NO production."

reach
"Endurance exercise training promotes endothelium dependent vasodilation XREF_BIBR - XREF_BIBR which is related to a shear stress induced and Akt dependent phosphorylation of endothelial NOS, resulting in NO activation."

reach
"Moreover, 17beta-E2-induced Akt activation actually enhances the phosphorylation of eNOS."

sparser
"Also AKT may phosphorylate eNOS to promote vasodilation with increased NO production in endothelial cells [ xref ]."

reach
"One target of Eph-B4 is Akt, which phosphorylates endothelial NO synthase (eNOS), a critical mediator of venous dilation (22)."

reach
"In addition, Akt phosphorylates and activates eNOS resulting in NO production and vasodilatation."

reach
"Various stimuli such as vascular endothelial growth factor (VEGF) activate Akt in ECs, resulting in Akt dependent phosphorylation of endothelial nitric oxide synthase (eNOS) to promote NO release; NO is a critical regulator of vascular tone and blood flow, and also regulates vascular remodelling and angiogenesis."

reach
"NO release occurs via PI3K-Akt dependent phosphorylation of eNOS with Src-kinase playing a proximal role in these changes."

sparser
"Activation of VEGFR2 in endothelial cells (by VEGF binding) results in the Akt-dependent phosphorylation of eNOS at Ser 1177 xref , xref , while VEGF treatment of BAECs resulted in the phosphorylation of eNOS at Ser 617 and Ser 635 (equivalent to human Ser 615 and Ser 633 ) xref ."

sparser
"Sphingosine 1–phosphate (S1P) similarly increases eNOS activity in a transient fashion, via a process that requires phosphorylation of eNOS by Akt upon activation of the EDG-1 receptor [ xref ]."

reach
"Therefore, the maintenance of baseline levels of VEGF in the endothelium is required to support vascular homeostasis.Activation of VEGFR2 in ECs via binding with a strong agonist, VEGF, results in Akt-dependent phosphorylation of eNOS as well as NO production [62] (Figure 1)."
| PMC

sparser
"NO production may also be induced via the phosphorylation of eNOS by AKT (Kasuno et al., xref )."

sparser
"This association is not only necessary for maintaining eNOS structure, but also for eNOS phosphorylation by Akt[ xref ]."

reach
"We evaluated the involvement of PI3K-Akt in telmisartan induced eNOS phosphorylation."

sparser
"In conclusion, S. crispa can ameliorate cerebrovascular endothelial dysfunction by promoting recovery of Akt-dependent eNOS phosphorylation and increasing nitric oxide (NO) production in the cerebral cortex."

reach
"ENOS, when phosphorylated by Akt, synthesizes the potent vasodilator nitric oxide."

reach
"Previous work has shown that AMPKalpha, Akt, Erk1/2 and PKA phosphorylate eNOS XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."

sparser
"ENOS is regulated by phosphorylation, and Akt phosphorylates eNOS and enhances the ability of eNOS to generate NO."

reach
"The PI3K and Akt pathway is likely to mediate eNOS phosphorylation and activation because the WS (R) 1442 stimulated eNOS phosphorylation can be abolished by the PI3K inhibitor wortmannin (Anselm et al., 2009)."

reach
"Most notably, VEGFR-2 activation recruits PI3-kinase, which in turn activates AKT which directly phosphorylates eNOS causing increased NO production."

reach
"We speculate that the binding of HO-1 to eNOS might alter the space conformation of eNOS, enhancing its interaction with Akt, subsequently facilitating the phosphorylation of eNOS by Akt."

sparser
"ENOS was phosphorylated by Akt in response to a variety of cellular stimuli [ xref ]."

reach
"The PI3K and Akt pathway is critical in the activation of NO signaling, e.g. phosphorylation of eNOS [XREF_BIBR], and the involvement of this pathway in the rapid effects of GCs has been documented [XREF_BIBR]."

reach
"The phosphorylation at Ser 1177 of eNOS plays an important role in the regulation eNOS activity and NO production [XREF_BIBR], and PI3K and Akt signaling is able to phosphorylate eNOS and increase NO production [XREF_BIBR]."

reach
"Maybe a hitherto unknown NOS interacting protein could mediate the effect in analogy to the described eNOS binding protein hsp90 which serves as a scaffold protein facilitating the phosphorylation and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"XREF_BIBR Akt inhibition diminished the phosphorylation of eNOS and reduced penile erection."

reach
"Being part of the same signalling pathway these results suggest that VEGF cell paracellular permeability involves the phosphoinositide 3-kinase–AKT pathway, which then further phosphorylates and activates endothelial nitric oxide synthase (eNOS) [49]."

sparser
"AKT can also phosphorylate eNOS and promote NO production xref , xref , enhancing blood flow, cell survival, morphogenesis, and angiogenesis, even in the setting of ischemia xref , xref ."

reach
"NO appears to have two roles in the development of an erection : a rapid, brief, calcium dependent activation of nNOS initiates the erectile process, whereas PI3K and Akt dependent phosphorylation of eNOS results in sustained NO production and thereby enables full erection attainment [XREF_BIBR, XREF_BIBR]."

sparser
"O‐GlcNAc increases in relation to high cellular glucose uptake and oxidative stress. xref , xref , xref Acutely, O‐GlcNAc modification is thought to play a protective role for cell survival against external stress‐inducing inflammation. xref , xref However, persistent elevation of intracellular O‐GlcNAc levels can cause chronic diseases including diabetic angiopathy. xref In T2DM, impaired activation of the insulin receptor/insulin receptor substrate/PI3K (phosphatidylinositol 3‐kinase)/Akt (protein kinase B)/endothelial nitric oxide synthase (eNOS) pathway is involved in endothelial dysfunction because insulin contributes to maintenance of chronic vasodilation via NO synthesis. xref , xref , xref , xref Prior experimental studies suggest that excessive O‐GlcNAc modification that occurred in proteins of the insulin receptor/insulin receptor substrate/PI3K/Akt/eNOS pathway can reduce NO production in endothelium. xref Hyperglycemia and hexosamine activation decrease phosphorylation of eNOS by Akt. xref Specifically, O‐GlcNAc competitively inhibits the binding site of eNOS phosphorylation by Akt. xref "

reach
"Small molecule Akt activator SC79 also induces eNOS phosphorylation and NO production in airway epithelial cells (84)."
| DOI

sparser
"Similarly, both Akt and AMPK can phosphorylate and activate eNOS, leading to increased NO production by cardiomyocytes."

reach
"For example, Kureishi etal report that in normocholesterolemic animals, serine threonine protein kinase Akt activated by simvastatin therapy enhances eNOS phosphorylation and thereby promotes angiogenesis."

sparser
"Estradiol–BSA activates eNOS identically to free estradiol by first activating Akt (Fig. 5) , which then phosphorylates eNOS resulting in enhanced activity and increased NO pro[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"LSS stimulates Akt phosphorylation, which in turn phosphorylates eNOS at Ser 1177, leading to eNOS activation and NO production 54."

reach
"Loss of PC protection was associated with age dependent reduced Akt phosphorylation and levels of eNOS and PKCepsilon in the hearts of mature animals compared with the younger ones, as well as with a failure of PC to upregulate these proteins."

reach
"Interestingly, as in endothelial cells exposed to shear stress (Dimmeler et al., 1999; Fulton et al., 1999), stimulation of myocardial eNOS activity in response to stretch is mediated by a PI (3) kina[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Despite this, there is some evidence that by phosphorylating eNOS, Akt can activate the enzyme at much lower Ca and calmodulin concentrations."

reach
"For instance, Akt mediates VEGF-A-induced cytoprotection [XREF_BIBR, XREF_BIBR], and contributes to EC function by directly phosphorylating eNOS, increasing Nitric Oxide bioavailability [XREF_BIBR]."

reach
"It has been reported that eNOS phosphorylation by PI3K and Akt pathway is required for efficient NO production [XREF_BIBR, XREF_BIBR], after phosphorylated at Ser 473 by PI3K, Akt in turn phosphorylates eNOS at Ser 1177 and thereby increases eNOS activity, and finally enhances NO production."

reach
"One recent study determined that male rats who underwent exercise training for 10 weeks after MI had increased Akt phosphorylation of eNOS, and reactivation of cardiac VEGF pathway activity, resulting in increased angiogenesis (155)."

reach
"Since it has been well established that PI 3 -kinase and Akt pathway regulates eNOS activity through phosphorylation at the pro active site (Ser1177), a PI 3 -kinase inhibitor LY-294002 was used to test whether LA induced eNOS phosphorylation is mediated by PI 3 -kinase and Akt pathway."

reach
"Erection of the penis is sustained by PI3K and Akt dependent phosphorylation and activation of eNOS, an NO producing enzyme [XREF_BIBR]."

reach
"We next investigated if SC79 could induce Akt-dependent phosphorylation of eNOS at the activating site S1177 in A549s."
| PMC

rlimsp
"In studies with purified proteins, HSP90 increased the initial rate and maximal extent of Akt-mediated eNOS phosphorylation and activation at low Ca2+ levels."

sparser
"Binding to caveolin-1 induces an inhibitory conformation of eNOS that is relieved upon Akt phosphorylation of eNOS."

reach
"Recent reports (Fulton et al., 1999; Dimmeler et al., 1999) indicate that the serine/threonine protein kinase Akt and PKB, which is a downstream substrate of PI3K phosphorylates and activates eNOS, le[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Finally, PKB phosphorylated eNOS in vitro at the same site phosphorylated in the cell and increased eNOS enzymatic activity by 15-20-fold."

sparser
"Phillip J. White et al. have reported that the Akt could promote the phosphorylation of eNOS to further improve the production of eNOS."

reach
"The subsequent increased arterial inflow to the cavernosal sinoids and shear stress on the endothelium lining penile arteries activates endothelial NO production through Akt phosphorylation of endothelial NO synthase (eNOS)."

reach
"However, this residual phosphorylation in Akt1 -/- mice was not sufficient to promote blood flow recovery and tissue healing, arguing that Akt phosphorylation of eNOS plays a critical role in adaptive angiogenesis."

sparser
"Dominant-negative Akt blocks VEGF-induced eNOS phosphorylation but not shear stress–induced eNOS phosphorylation, whereas the PKA inhibitor H89 blocks shear stress–induced eNOS phosphorylation but not eNOS phosphorylation by constitutively active Akt ( xref )."

sparser
"NO, as an important angiogenesis-mediating factor, is induced by angiogenic factors through activating Akt-dependent eNOS phosphorylation."

sparser
"In addition, Akt phosphorylates and activates eNOS resulting in NO production and vasodilatation. xref Therefore, insulin resistance states exhibit impaired insulin-mediated vasodilatation. xref "

sparser
"The production of NO via an endothelial type of NO synthase (eNOS) occurs primarily through an increase in cytosolic Ca 2+ concentration ([Ca 2+ ] c ) in the endothelium and Akt-dependent phosphorylation of eNOS ( xref )."

sparser
"The signaling of NO production through ET-B receptors via the G-protein βγ subunit dimer has been linked to AKT phosphorylation of eNOS."

sparser
"Activated Akt can phosphorylate eNOS, thereby promoting the production of endogenous NO, accelerating the regeneration of vascular endothelial cells, and dilating blood vessels."

rlimsp
"Thus, phosphorylation of eNOS by Akt represents a novel Ca2+-independent regulatory mechanism for activation of eNOS."

reach
"In addition, data shown in XREF_FIG, provide evidence that BAR501, exerts non genomic effects in LSEC, causing an Akt dependent phosphorylation of CSE and eNOS."

reach
"The activation of eNOS could be achieved by its phosphorylation at Ser 1177, and this eNOS phosphorylation can be triggered by the activation of protein kinase Akt (also known as protein kinase B) and phosphoinositide-3-kinase (PI3 kinase) XREF_BIBR."

reach
"Intriguingly, PKB and Akt and eNOS were able to bind simultaneously to the middle segment of Hsp90, which appeared able to " scaffold " their interaction and facilitate phosphorylation of eNOS by PKB [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"PLC-gamma associated intracellular Ca 2+ flux is associated with calmodulin mediated activation of eNOS, but eNOS activation may also be directly mediated by AKT phosphorylation of eNOS on S 1177 in Ca 2+ -independent manner."

sparser
"In the condition of fluid shear stress, phosphorylation of eNOS by Akt represents the most important pathway for eNOS activation [ xref , xref ]."

sparser
"Current studies consistently show that equol rapidly acts upon eNOS synthesis so possible mechanism for equol activity could be activation of membrane bound ER (GPR30) xref , which in turn, activates Akt kinases that phosphorylate eNOS and activate Nrf2 xref ."

reach
"In endothelial cells, Akt is a downstream effector of PI-3K signaling, and can phosphorylate eNOS and stimulate production of NO (Fulton et al. 1999)."

reach
"We and other authors reported the phosphorylation of eNOS by Akt and PKB XREF_BIBR - XREF_BIBR and AMPK XREF_BIBR both in vitro and in a cellular environment."

sparser
"Indeed, Akt can directly phosphorylate eNOS, leading to NO production."

sparser
"HDL triggers the activation (phosphorylation) of Akt and Akt dependent phosphorylation and activation of eNOS in endothelial cells both in culture and in vivo [ xref , xref ]."

reach
"On activation, Akt phosphorylates eNOS leading to increased nitric oxide production."

reach
"Activation of Akt stimulates phosphorylation of eNOS, production of nitric oxide and reduces oxidative stress."

reach
"On insulin stimulation, eNOS is phosphorylated by the activation of PI3k and Akt pathway in vascular endothelial cells."

sparser
"NO production may also be induced via the phosphorylation of eNOS by AKT (Kasuno et al., 2004)."

reach
"Estradiol-BSA activates eNOS identically to free estradiol by first activating Akt, which then phosphorylates eNOS resulting in enhanced activity and increased NO production."

reach
"Furthermore, phosphorylation of eNOS and NO production can be upregulated by the PI3-K and AKT pathway in the angiogenesis of endothelial cells (Tanimoto et al., 2002)."

sparser
"Statins also increase eNOS activity by post-translational activation of the PI3K/Akt pathway as eNOS is phosphorylated by Akt [ xref ]."

reach
"Indeed, Akt can directly phosphorylate eNOS, leading to NO production."

reach
"We also observed an increase in phosphorylation of eNOS with overexpressed PDCD4 and a decrease with downregulated PDCD4, which disagrees with the finding that PDCD4 blocks the phosphorylation of Akt, whereas activated Akt phosphorylates eNOS XREF_BIBR, XREF_BIBR."

reach
"Angiotensin (1-7) stimulates a transmembrane receptor Mas, which cascades to Akt phosphorylation and activation of endothelial NO synthase (eNOS), thereby increasing NO production."
| PMC

reach
"It has been reported that eNOS is phosphorylated by PKB, increasing NO production causing vasodilation while vasoconstriction is the result of endothelin-1 production as a consequence of the activation of the MAPK pathway [XREF_BIBR]."

reach
"Akt is a common protein kinase involved in numerous cellular signaling pathways, including the phosphorylation of eNOS via serine1177; eNOS synthesizes NO [59]."

sparser
"In agreement with our data, it has been recently shown that rapid eNOS activation can be accomplished by eNOS phosphorylation by Akt [48,49] ."

reach
"In fact, EPO activates (through the EPO-R) the PI3 kinase / Akt signaling pathway and thus increases both eNOS expression and phosphorylation."

reach
"Dimmeler et al 44 show that activation of Akt enhances eNOS phosphorylation and cardioprotective signaling through NO."

sparser
"We conclude that insulin regulates eNOS activity using a Ca(2+)-independent mechanism requiring phosphorylation of eNOS by Akt."

reach
"MPA attenuated the E2 induced phosphorylation of Akt, a kinase that phosphorylates eNOS."

reach
"It has been reported that in ECs, eNOS is phosphorylated by the Akt protein kinase, resulting in an increase in eNOS activity."

reach
"To understand the mechanism further, XREF_BIBR have shown that activated protein kinase B (Akt) phosphorylates eNOS and increases the production of NO."

sparser
"In conclusion, S. crispa could ameliorate cerebrovascular endothelial dysfunction by promoting recovery of Akt-dependent eNOS phosphorylation and increasing NO production in the cerebral cortex."

reach
"Previous work revealed that the Akt dependent phosphorylation of eNOS mediates penile erection 18."

sparser
"Akt is activated by PI3K and phosphorylates eNOS to promote the synthesis and release of endogenous nitric oxide, which protects vascular endothelial cells [ xref , xref ]."

reach
"Previously studies have demonstrated that Akt directly phosphorylates and activates eNOS in endothelial cells XREF_BIBR."

reach
"In the medullary thick ascending limb, ET-1 activates phosphatidylinositol 3-kinase (PI3K), inducing phosphorylation and activation of Akt, which in turn phosphorylates eNOS, resulting in increased NO production and inhibition of sodium reabsorption [XREF_BIBR]."

sparser
"Endothelium-derived nitric oxide is another important promoter of VP and is produced by eNOS. xref , xref Phosphorylation of eNOS by AKT is required for efficient production of nitric oxide. xref However, eNOS inhibitors had no effect on Fg-induced VP, suggesting that Fg/AKT-induced VP is independent of eNOS pathway."

reach
"Phosphorylation of endothelial nitric oxide synthase (eNOS) by Akt is also necessary for its activation by insulin."

sparser
"We conclude that erectile ability can be enhanced under preconditions of erectile impairment by long-term inhibition of phosphodiesterase-5 and that the effect is mediated by Akt-dependent eNOS phosphorylation."

reach
"The role of p38 MAPK and Akt in H 2 S induced eNOS phosphorylation and NO production."

sparser
"Because Akt and eNOS are both localized in the bladder urothelium, phosphorylation of eNOS by Akt provides an attractive mechanism for rapid increases in urinary NO production."

reach
"This is believed to result from the anti-inflammatory effects of endothelially derived nitric oxide, due to a preconditioning induced Akt dependent phosphorylation of endothelial NOS (Hashiguchi et al., 2004, Furuya et al., 2005) that enhances nitric oxide activity (Puisieux et al., 2000, Furuya et al., 2005)."

sparser
"We speculate that TSP-1 inhibits VEGFR2 phosphorylation by abolishing the close association of CD47 and VEGFR2, thus suppressing Akt phosphorylation and activation of eNOS, and finally resulting in attenuation of angiogenesis xref ."

sparser
"Therefore, the cilostazol-induced production of NO x species in the present work may be mediated by eNOS phosphorylation by Akt, the activation of protein kinase A (PKA), due to increased intracellular cAMP or an unknown pathway."

sparser
"This supports a theory that hsp90 plays a key role in activating eNOS by serving as s docking site for AKT-dependent phosphorylation of eNOS and that calpain over activation regulates hsp90 function. ( xref )"

reach
"Many growth factors and hormones can promote PI3K and Akt dependent phosphorylation of eNOS, which activates NOS and stimulates the subsequent increase in NO production [XREF_BIBR, XREF_BIBR]."

reach
"37 The mechanisms in estrogen induced eNOS activation and NO expression on ECs are that estrogen activates PI3K and protein kinase B (Akt) pathways, which lead to phosphorylation and activation of eNOS and increases NO production."

reach
"We conclude that insulin regulates eNOS activity using a Ca (2+)-independent mechanism requiring phosphorylation of eNOS by Akt."

sparser
"Akt phosphorylates eNOS and thereby enhances activity [ xref ]."

sparser
"We found that purified Akt phosphorylated cardiac eNOS at Ser1177, resulting in activation of eNOS."

reach
"Additionally, although it is not clearly understood at this time, it has been demonstrated that statins stimulate activity in the PI3K and AKT pathway, which ultimately leads to eNOS phosphorylation and NO production [XREF_BIBR, XREF_BIBR]."

reach
"Vitexin significantly preserved eNOS phosphorylation in response to the activated Akt."

reach
"Prior studies have shown that phosphorylation of eNOS by Akt causes prolonged NO production and maximal construction and influences penile erection (Zhang et al., 2011)."

reach
"Notably, all the pathological changes (arginase induction, L-arginine deficiency, Akt inhibition and reduced eNOS phosphorylation) in diet induced obese mice were observed only in the PVAT but not in the aorta itself (Xia et al., 2016)."

reach
"Sphingosine 1-phosphate (S1P) similarly increases eNOS activity in a transient fashion, via a process that requires phosphorylation of eNOS by Akt upon activation of the EDG-1 receptor [XREF_BIBR]."

reach
"The activated PI3K and Akt signaling leads to phosphorylation of eNOS and increases the production of NO [XREF_BIBR]."

reach
"Recently, Besler et al. demonstrated that, through a course involving the endothelial LOX-1, " dysfunctional-HDL " actuates endothelial PKCbetaII, which in turn inhibits Akt activating phosphorylation and eNOS activating phosphorylation events and eNO production."

sparser
"In turn, phosphorylated AKT induced phosphorylation of eNOS, converting eNOS into its active form [ xref ]."

reach
"However, insulin has calcium independent vasodilator actions that are mediated by a phosphatidylinositol 3-kinase-dependent mechanism involving phosphorylation of eNOS by Akt [XREF_BIBR, XREF_BIBR]."

sparser
"In fact, simvastatin administration increases eNOS expression, Akt-dependent eNOS phosphorylation and cGMP liver content."

reach
"Akt, a serine/threonine kinase, phosphorylates eNOS thereby activating the enzyme."

reach
"In porcine coronary artery rings, HEDS also causes endothelium dependent relaxation via redox sensitive activation of the endothelial PI3-kinase and Akt pathway, which leads to eNOS phosphorylation [XREF_BIBR]."

reach
"Phosphorylation of eNOS and NO production were mediated by Akt and then regulated angiogenesis [XREF_BIBR] (XREF_FIG)."

reach
"PI3K and AKT signaling phosphorylates endothelial nitric oxide synthase (eNOS and NOS3), which plays a major role in neural transmission through axons."

sparser
"A previous study suggested the potential role of Akt-dependent signaling in the beneficial effects of TH after CA. xref Since Akt phosphorylates NOS3, we examined expression of phosphorylated Akt in the brain of WT mice resuscitated from CA/CPR."

sparser
"Activation of VEGFR2 in ECs via binding with a strong agonist, VEGF, results in Akt-dependent phosphorylation of eNOS as well as NO production [ xref ] ( xref )."
| PMC

sparser
"When Akt phosphorylates eNOS at serine, NO production starts with amino acid L-arginine oxidation to generate NO and L-citrulline [ xref ]."

reach
"[3] Additionally, evidence has shown that Akt, a downstream target of phosphatidylinositol 3-kinase (PI3K), also activates eNOS phosphorylation in endothelial cells [5]."

sparser
"This signalling pathway controls a number of critical mechanisms, including phosphorylation of eNOS by Akt."

reach
"Furthermore, the antiapoptotic actions of kallistatin were accompanied by Akt mediated FOXO1 and eNOS phosphorylation, as well as increased NOS activity."

reach
"Intriguingly, PKB and Akt and eNOS were able to bind simultaneously to the middle segment of Hsp90, which appeared able to " scaffold " their interaction and facilitate phosphorylation of eNOS by PKB [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The insulin signaling cascade activates protein kinase B (Akt), which in turn phosphorylates and activates eNOS in ECs."

reach
"Moreover, since phosphorylation of eNOS by the upstream kinase Akt is an important mechanism regulating activation of eNOS in response to several ligands, the phosphorylation levels of eNOS and Akt were concomitantly measured in both WKY and SHR preparations."

reach
"PI3K is an intracellular signal transducer that activates the downstream target AKT that is able to phosphorylate eNOS."

reach
"We and other authors reported the phosphorylation of eNOS by Akt and PKB XREF_BIBR - XREF_BIBR and AMPK XREF_BIBR both in vitro and in a cellular environment."

sparser
"In the cultured EC, it is reported that the production of NO is controlled by Akt-dependent phosphorylation of eNOS."

reach
"This action enhances phosphorylation of eNOS by serine/threonine protein kinase Akt, XREF_BIBR increases nitric oxide release, XREF_BIBR and facilitates cyclic guanosine monophosphate production."

reach
"After it was demonstrated that Akt, the downstream target of PI3K, phosphorylates eNOS and potentiates Ca and calmodulin association (Fulton et al., 1999), Haynes et al. (2000) used human umbilical vein endothelial cells (HUVECs) and EA hy926 (human endothelial-like) cells to evaluate E2’s ability to activate Akt by binding cellular membrane receptors."

reach
"The stimulatory phosphorylation of eNOS residues Ser 1177 and Ser 617 occur in response to flow shear stress that activates phosphatidyl-inositol 3-kinase (PI3K) and its downstream serine/threonine protein kinase, Akt, which in turn phosphorylates eNOS (PI3K-Akt-eNOS pathway) XREF_BIBR, XREF_BIBR, XREF_BIBR."

sparser
"Akt phosphorylates eNOS at Ser 1177 in the C-terminal reductase domain, which increases electron flow and augments calcium-CaM sensitivity of the enzyme ( xref – xref )."

reach
"In endothelial cells, growth factors such as VEGF can stimulate AKT mediated phosphorylation of eNOS [XREF_BIBR]."

sparser
"Moreover, Akt also phosphorylates and activates eNOS, which we showed with the tumors (Fig.  xref p and q) and confirmed here (Fig. xref r and s)."
| PMC

reach
"TNF-alpha, even at the lowest dose of 1 ng/ml, completely blunted insulin stimulated Akt phosphorylation (Ser 473) (XREF_FIG A), thus increasing eNOS phosphorylation at the inhibitory site (Thr 495) (XREF_FIG B)."

sparser
"Mechanistically, PGC-1α was found to inhibit Akt phosphorylation of eNOS, which is essential for angiogenesis [ xref ]."

sparser
"The binding of CaM to eNOS allows Akt to phosphorylate eNOS in both human and animal models at serine 1177 and serine 1179 , respectively, while at the same time, Akt causes dephosphorylation at the inhibitory site of eNOS at threonine 495 (Thr 495 ) [ xref , xref ]."

sparser
"PI3K/Akt signaling pathway is a predominantly cell-survival and cytoprotective pathway in many cell types. xref APC activates the PI3K/Akt pathway in the endothelial cells in EPCR-and PAR1-dependent manner. xref Akt directly phosphorylates GSK3β and eNOS, which promote cell survival and barrier stabilization pathways. xref , xref Our present data show that FVIIa activates the Akt pathway and induces the phosphorylation of Akt substrates GSK3ß and eNOS."

reach
"In addition, enhanced Akt phosphorylation and protein levels of eNOS, in conjunction with blunting of cardioprotection by NOS inhibitor L-NAME, were observed in the WY treated hearts."

reach
"Overexpression of XBP1s increases Akt phosphorylation [XREF_BIBR], whereas the phosphorylation of NOS3 by Akt represents a major Ca 2+ - independent regulatory mechanism for the activation of eNOS [XREF_BIBR]."

reach
"Upon stimulation by agents such as VEGF, the binding of eNOS and Cav-1 is released, eNOS associates with calmodulin, and then subsequently phosphorylated by heat shock protein 90 and AKT 23."
| PMC

reach
"S1P activated the phosphatidylinositol-3-kinase (PI3K)/Akt/endothelial NO synthase (eNOS) pathway in ECs, since S1P stimulated eNOS phosphorylation and NO production were blocked by inhibition of activities of PI3K and Akt."

sparser
"For example, shear-stress-mediated eNOS activation indicates that eNOS phosphorylation induced by Akt was a typical Ca 2+ -dependent regulatory mechanism for activation of eNOS [ xref ]."

reach
"This PI3K increase activated Akt which phosphorylated eNOS to generate NO in HUVECs."

sparser
"The Akt-dependent eNOS phosphorylation did not seem to be a primary molecular adaptation in response to long-term exercise in healthy mice."

reach
"Akt can also phosphorylate eNOS to increase eNOS stability and coupling [XREF_BIBR]."

reach
"For example, shear-stress-mediated eNOS activation indicates that eNOS phosphorylation induced by Akt was a typical Ca 2+ -dependent regulatory mechanism for activation of eNOS [XREF_BIBR]."

reach
"We focused on a well described pathway stemming from beta1 integrin to SFK and PI3 Kinase and Akt which ultimately phosphorylates and activates eNOS."

reach
"NO production may also be induced via the phosphorylation of eNOS by AKT (Kasuno et al., 2004)."

reach
"Akt can directly phosphorylate eNOS [XREF_BIBR]."

sparser
"VEGFR2 increases permeability of the vascular endothelium by activation of endothelial nitric oxide synthase through AKT induced phosphorylation of eNOS or via PLCγ dependent Ca2+ influx with the subsequent increase in production and level of nitric oxide (NO) ( xref )."

sparser
"ENOS is a known substrate of Akt [ xref ], and phosphorylation and activation of eNOS by Akt, inducing an increase in NO production, is indeed observed in myocardial ischemia [ xref ]."

sparser
"Thus, phosphorylation of eNOS by Akt represents a novel Ca2+-independent regulatory mechanism for activation of eNOS."

reach
"Although eNOS is phosphorylated and activated by multiple upstream kinases, Akt dependent phosphorylation of eNOS seems to play an essential role in angiogenesis, i.e. Akt-eNOS signaling axis controlling angiogenesis therby regulating blood flow and tissue repair [XREF_BIBR]."

reach
"The activation of the PI3-K and Akt pathway further increased the expression and phosphorylation of eNOS and promoted the production of NO."

reach
"Taken together, our novel findings suggest that the EDR induced by the strawberry extract was mediated by activation of the PI3 kinase and Akt signaling pathway, resulting in phosphorylation of eNOS."

reach
"Fulton et al. [XREF_BIBR] demonstrated that Akt directly phosphorylates eNOS, thereby enhancing eNOS activity and NO production."

sparser
"Recent evidence demonstrated that NADPH oxidase-mediated ROS regulates Akt phosphorylation and activation of eNOS [ xref ]."

reach
"PI3K activated by the adherens junction mechanosensory complex also phosphorylates Akt, which then phosphorylates eNOS to stimulate NO release XREF_BIBR, XREF_BIBR."

reach
"As shown in XREF_FIG, hyperlipidemia significantly impaired Akt and eNOS phosphorylation, whereas U50,488 H significantly restored Akt and eNOS phosphorylation."

sparser
"Interestingly, as in endothelial cells exposed to shear stress ( Dimmeler et al., 1999 ; Fulton et al., 1999 ), stimulation of myocardial eNOS activity in response to stretch is mediated by a PI(3)ki[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Active Akt can phosphorylate and activate eNOS [ xref ]."

sparser
"XAT increased nitric oxide production and Akt- endothelial NOS (eNOS) phosphorylation in HUVECs."

reach
"Current studies consistently show that equol rapidly acts upon eNOS synthesis so possible mechanism for equol activity could be activation of membrane bound ER (GPR30) XREF_BIBR, which in turn, activates Akt kinases that phosphorylate eNOS and activate Nrf2 XREF_BIBR."

reach
"Several growth factors activate protein kinase Akt and PKB which can phosphorylate endothelial NOS to promote NO synthesis [XREF_BIBR, XREF_BIBR]."

sparser
"It has been reported that shear stress-induced NO production seems to be controlled by the Akt-dependent phosphorylation of eNOS in cultured ECs xref ."

sparser
"The aim of the present study was to investigate the effects of exercise training on the endothelial function in relation to the expression of eNOS and Akt-dependent eNOS phosphorylation in the left internal mammary artery (LIMA) of patients with stable CAD."

reach
"Moreover, selenium enhanced AKT phosphorylation, and selenium induced phosphorylation and expression of eNOS were inhibited by AKT inhibition."

sparser
"It has been reported that eNOS is phosphorylated by PKB, increasing NO production causing vasodilation while vasoconstriction is the result of endothelin-1 production as a consequence of the activation of the MAPK pathway [ xref ]."

sparser
"Akt phosphorylates eNOS, and activation of the pathway therefore increases eNOS activity [ xref ]."

reach
"For example, the NO production in responding to shear stress was controlled by the Akt dependent phosphorylation of eNOS in cultured HUVECs [XREF_BIBR]."

rlimsp
"We therefore explored if PP2A might reduce eNOS activation by impairing the subcellular pool of Akt that colocalizes with and phosphorylates eNOS."

sparser
"Other studies revealed that Akt-dependent phosphorylation and activation of eNOS leads to sustained NO production and maximal erection xref , xref ."

sparser
"We further reveled that lack of Ng expression decreases both AKT-dependent eNOS phosphorylation, NF-κB-mediated eNOS expression, and promotes endothelial activation."

sparser
"Given the knowledge that VEGF-A, via Akt phosphorylation of eNOS, stimulates NO production from EC ( xref , xref ) and that NO reportedly upregulates BDNF ( xref ), it is possible that eNOS-derived NO is involved in the VEGF-A-induced increase in BDNF."

reach
"CSE treatment impaired both VEGF- and FSS mediated VEGFR2 phosphorylation, resulting in impaired endothelial nitric oxide synthase (eNOS) phosphorylation by Akt."

sparser
"Phosphorylation of NOS3 by protein kinase AKT can also increase the enzyme activity of NOS3 [ xref ]."

reach
"These results indicate that both Erk1/2 and Akt signaling could potentially mediate the enhanced eNOS phosphorylation and NO production to promote endothelial function and angiogenesis by FMNT in vitro and in vivo."

reach
"These stimuli increase NO production in endothelial cells through an insulin receptor substrate-1 (IRS-1-) and phosphatidylinositol 3-kinase (PI3-kinase-) dependent pathway that causes phosphorylation of endothelial nitric oxide synthase (eNOS) by Akt [XREF_BIBR]."

reach
"The second is phosphorylation of eNOS by PKC and AKT (both of which are activated by PI3K), which leads to further activation of eNOS."

reach
"Akt promotes the phosphorylation of endothelial nitric oxide synthase (eNOS) generating NO, which could stimulate angiogenesis [XREF_BIBR, XREF_BIBR]."

reach
"Previous studies showed that shear stress dependent phosphorylation of eNOS was mediated by a PKA dependent and Akt independent mechanism, suggesting that PKA plays a critical role in shear stress dependent activation of eNOS."

sparser
"Additionally, Akt may phosphorylate vascular eNOS and consequently enhance NO production, leading to restrained platelet aggregation and TF expression ."

sparser
"Akt may phosphorylate the vascular eNOS and enhance NO production (Yang and Loscalzo, 2000)."

reach
"By using various inhibitors here, the eNOS phosphorylation and NO production triggered by NRR volatile oil could be mediated by both Akt and CaM kinase activation."

sparser
"Erectile function of aged rats can lastingly be enhanced by long-term inhibition of phosphodiesterase (PDE)5 with sildenafil by rescuing Akt-dependent phosphorylation of eNOS (Ser-1177) in the penis ( xref )."

reach
"Akt has been determined to activate the phosphorylation of eNOS, inhibit apoptotic processes, thus interfering with cellular survival pathways."

sparser
"While Akt can produce stimulatory phosphorylations of eNOS, it might also activate NF-kB, which in turn can initiate eNOS transcription xref , xref , xref ."

reach
"High-shear-stress-stimulated NO production is well known to require the multisite phosphorylation of endothelial nitric oxide synthase (eNOS) by Akt, protein kinase A (PKA), or protein kinase C."

sparser
"We also suggest that fluvastatin would ameliorate vascular endothelial dysfunction, in part, presumably via its recovery effect on Akt-dependent eNOS phosphorylation."

reach
"Thus far, it has been reported that HSP90 stimulates the NO production through the association with Akt and eNOS directly [30] and the aid to Akt driven phosphorylation of eNOS protein [31]."

sparser
"Shear stress activates the PI-3 kinase/Akt pathway, Akt phosphorylates e-NOS and enhances the production of NO, which S-nitrosylates caspases thereby inhibiting their activity and apoptosis [94] ."

reach
"Upon exposure to shear stress, eNOS translocates from caveolae to the cytoplasm, where eNOS is phosphorylated by Akt."

reach
"As Akt phosphorylates eNOS and therefore is able to promote NO bioavailability and impact EDR in large vessels, we determined the ratio of phosphorylated to total Akt in aortas from young and old rats."

reach
"One such signal is the Akt dependent phosphorylation of endothelial nitric oxide synthase (eNOS), which contributes to stimulation of NO release and vessel relaxation XREF_BIBR."

reach
"Also AKT may phosphorylate eNOS to promote vasodilation with increased NO production in endothelial cells [XREF_BIBR]."

sparser
"This phosphorylated Hsp90, in turn, serves as a scaffold to facilitate the association between eNOS and AKT, thereby promoting AKT-dependent phosphorylation and activation of eNOS ( xref ) [ xref ]."

sparser
"In addition, data shown in xref , provide evidence that BAR501, exerts non genomic effects in LSEC, causing an Akt-dependent phosphorylation of CSE and eNOS."

reach
"It has been reported that the Akt dependent phosphorylation of eNOS is necessary for the full activation of eNOS and endothelium dependent vasorelaxation, and so impaired PI3K and Akt activation may have been involved in the reduced endothelium dependent vasorelaxation."

sparser
"Akt phosphorylation and activation of endothelial NOS (eNOS) stimulates RNS-dependent oxidation or S-nitrosylation of Cys 118 of Ras resulting in cytoprotective signaling through Akt."

reach
"Recently, it has been shown that the serine threonine kinase, AKT, phosphorylates eNOS in vitro as well as in vivo (Dimmeler et al., 1999; Fulton et al., 1999) and, by doing so, it causes a sustained [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The signaling of NO production through ET-B receptors via the G protein betagamma subunit dimer has been linked to AKT phosphorylation of eNOS."

reach
"We therefore reasoned that the dissociation of eNOS phosphorylation and NO synthesis specific to insulin stimulated cells implies that stimulation of Akt and subsequent phosphorylation of eNOS may be required, yet insufficient, for insulin stimulated NO synthesis in cells cultured in high glucose."

sparser
"In the medullary thick ascending limb, ET-1 activates phosphatidylinositol 3-kinase (PI3K), inducing phosphorylation and activation of Akt, which in turn phosphorylates eNOS, resulting in increased NO production and inhibition of sodium reabsorption [ xref ]."

reach
"Binding to caveolin-1 induces an inhibitory conformation of eNOS that is relieved upon Akt phosphorylation of eNOS."

reach
"Membrane bound eNOS is estimated to be more constitutively active and usually phosphorylated by Akt for activation."

rlimsp
"The activity of NOS3 is also increased by its phosphorylation by Akt [16]."

reach
"The vascular endothelial growth factor (VEGF) contributes to activation of eNOS by Ca2 +/calmodulin and also stimulates the protein kinase Akt, which directly phosphorylates eNOS on Ser1177 and increases enzyme activity."

reach
"VEGF has been shown to activate NO release through AKT dependent phosphorylation of eNOS [XREF_BIBR, XREF_BIBR - XREF_BIBR]."

reach
"While Akt can produce stimulatory phosphorylations of eNOS, it might also activate NF-kB, which in turn can initiate eNOS transcription XREF_BIBR, XREF_BIBR, XREF_BIBR."

reach
"Endothelial nitric oxide synthase (eNOS) is a known downstream target of Akt, which has recently been shown to phosphorylate eNOS, leading to persistent activation [XREF_BIBR], and contribute to postnatal neovascularization [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

reach
"These data suggest that shear stress activates a pathway involving PI3K and the serine/threonine kinase Akt, which phosphorylates eNOS."

reach
"XREF_BIBR, XREF_BIBR Under these conditions, activation of GPER by G-1 resulted in reduced myocardial expression of proinflammatory cytokines (IL-1beta, IL-6 and tumor necrosis factor), 145 increased activation of Akt, 132 ERK1/2, XREF_BIBR, XREF_BIBR increased phosphorylation of eNOS 132 and decreased mitochondrial permeability."

reach
"The evidence shows that inhibits the activity of PI3K and Akt can decrease the phosphorylation of eNOS (H. Zheng, Fu, Dai, and Huang, 2007)."

reach
"In vitro, acute insulin signaling activated eNOS phosphorylation mediated by PI3K and Akt signaling in LECs, but prolonged hyperinsulinemia and hyperglycemia promoted insulin resistance, impaired PI3K/Akt/eNOS signaling, mitochondrial function, and NO bioavailability, and also increased lymphatic permeability."

reach
"In contrast, Boo et al. showed that laminar shear stress stimulates phosphorylation of eNOS by protein kinase A but not Akt XREF_BIBR."

sparser
"In activating eNOS, HDL binding to SR-BI activates Src, which leads to Akt activation, and Akt then phosphorylates eNOS[ xref ]."

reach
"Since Akt can modulate eNOS phosphorylation, we examined if it was differentially phosphorylated (S476)."

sparser
"Since Akt phosphorylates and activates eNOS [ xref ], which plays a role in regulation of cell adhesion [ xref , xref ], we analyzed the role of Akt in regulation of eNOS coupling after UVB-irradiation using a SDS-resistant reducing gel [ xref ]."

reach
"We speculate that TSP-1 inhibits VEGFR2 phosphorylation by abolishing the close association of CD47 and VEGFR2, thus suppressing Akt phosphorylation and activation of eNOS, and finally resulting in attenuation of angiogenesis XREF_BIBR."

reach
"In mutant Ras transformed cells, Akt phosphorylation and activation of eNOS results in the S nitrosylation (or oxidation to sulfenic acid) of Ras Cys118, enhancing GTP binding, and thereby stimulating cytoprotective signaling pathways XREF_BIBR."

reach
"This indicates a significant Akt activation, which in turn could promote eNOS phosphorylation and renal protection."

reach
"Hsp90 serves a scaffolding function to facilitate Akt mediated phosphorylation of eNOS in the calveolae [XREF_BIBR - XREF_BIBR]."

reach
"This supports a theory that hsp90 plays a key role in activating eNOS by serving as s docking site for AKT dependent phosphorylation of eNOS and that calpain over activation regulates hsp90 function."

rlimsp
"Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Akt-dependent phosphorylation of endothelial nitric oxide synthase and NO release."

reach
"Akt has been shown to increase eNOS phosphorylation, resulting in activation of eNOS, and experiments with eNOS knockout mice indicate a role for NO in protection against ischemic damage."

sparser
"Among these, Akt-dependent eNOS phosphorylation is essential for angiogenesis (Kureishi et al., 2000)."

reach
"Recent studies demonstrated that S1P activation of S1P 1 results in Akt dependent phosphorylation of eNOS and increased NO [50,51,53,75]."

reach
"In response to various forms of cellular stimulation, eNOS is phosphorylated by AKT and PKB [XREF_BIBR]."

reach
"Taken together, these findings suggest that the endothelium dependent relaxation induced by the GSE was mediated by activation of the PI3K and Akt signalling pathway through a redox sensitive mechanism, resulting in phosphorylation of eNOS."

sparser
"Hsp90 binding increases the affinity of Akt for eNOS and/or unmask the phosphorylation sites on eNOS, which increases the rate of Akt-dependent eNOS phosphorylation [ xref ; xref ]."

reach
"It has been reported that shear stress induced NO production seems to be controlled by the Akt dependent phosphorylation of eNOS in cultured ECs XREF_BIBR."

reach
"In response to various forms of cellular stimulation, eNOS is phosphorylated by AKT and PKB [XREF_BIBR]."

reach
"This kinase activates Akt which further phosphorylates eNOS leading to Ca2+ independent enzyme activation."

sparser
"VEGF has been shown to activate NO release through AKT-dependent phosphorylation of eNOS [ xref , xref - xref ]."

sparser
"Moreover, since phosphorylation of eNOS by the upstream kinase Akt is an important mechanism regulating activation of eNOS in response to several ligands, the phosphorylation levels of eNOS and Akt were concomitantly measured in both WKY and SHR preparations."

reach
"Akt inhibition prevented NOS3 phosphorylation."

reach
"Akt phosphorylates eNOS and thereby enhances activity [XREF_BIBR]."

reach
"Fulton et al. [XREF_BIBR] and Skaletz-Rorowski et al. [XREF_BIBR] demonstrated that Akt phosphorylates eNOS, while mevalonate inhibits phosphatidylinositol-3 kinase and thereby reduces Akt activation."

reach
"Akt is activated by PI3K and phosphorylates eNOS to promote the synthesis and release of endogenous nitric oxide, which protects vascular endothelial cells [XREF_BIBR, XREF_BIBR]."

reach
"We confirmed that upon stimulation with VEGF, Akt phosphorylates eNOS in an HSP90 dependent manner; synergistically increasing eNOS activity."

sparser
"Recent studies demonstrated that S1P activation of S1P results in Akt-dependent phosphorylation of eNOS and increased NO ."

reach
"These results indicate that E 1 induces PI3K mediated stimulation of Akt, leading to eNOS phosphorylation.Soluble guanylate cyclase (sGC) is the main target for NO and accounts for the conversion of G[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Akt is also involved in transducing the cellular actions of GLP-1 or exendin-4 ( Idris et al., 2002; Buteau et al., 1999; Hui et al., 2003; Redondo et al., 2003 ), being an essential mediator linking [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"On the one hand, simvastatin treatment improved liver sinusoidal endothelial dysfunction by increasing Akt-dependent endothelial NOS (eNOS) phosphorylation (activity) and eNOS gene expression [ xref , xref ]."

reach
"Ang-2 in high concentrations induces robust phosphorylation of Tie2 XREF_BIBR and prevents endothelial cell apoptosis XREF_BIBR through activation of the pro survival Akt pathway, which can phosphorylate eNOS."

reach
"Akt also increases VEGF secretion and mediates eNOS phosphorylation, vasorelaxation and angiogenesis."

reach
"Endothelial NOS is also phosphorylated by Akt and other upstream kinases (Fulton etal.,1999)."

sparser
"Phosphorylation of eNOS by protein kinase B (PKB or AKT) at this site activates the enzyme and positively regulates penile erection."

sparser
"In addition, HOCl treatment alone as well as HOCl added with Akt inhibitor MK2206 inhibited phosphorylation of Akt and eNOS, reducing NO production."

reach
"S1P stimulated eNOS phosphorylation and NO production is blocked by inhibition of PI3K or Akt XREF_BIBR."

sparser
"In mutant Ras transformed cells, Akt phosphorylation and activation of eNOS results in the S-nitrosylation (or oxidation to sulfenic acid) of Ras Cys118, enhancing GTP binding, and thereby stimulating cytoprotective signaling pathways xref ."

rlimsp
"Activated Akt phosphorylates several downstream targets including eNOS [11]."

reach
"This is consistent with previous studies showing that inhibition of Rho-kinase increases eNOS mRNA stability, 18 and can lead to the rapid activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway, which can phosphorylate and activate eNOS."

sparser
"Fulton et al. [ xref ] demonstrated that Akt directly phosphorylates eNOS, thereby enhancing eNOS activity and NO production."

sparser
"It has been reported that the Akt-dependent phosphorylation of eNOS is necessary for the full activation of eNOS and endothelium-dependent vasorelaxation, and so impaired PI3K/Akt activation may have been involved in the reduced endothelium-dependent vasorelaxation ( xref ; xref )."

sparser
"PKB and PKC phosphorylate their downstream eNOS at the serine 1,177 and 633 sites, respectively, initiating an immediate NO synthesis ( xref )."

sparser
"PKB phosphorylates eNOS, increasing NO production and vasodilation, while the MAPK pathway results in endothelin-1 production and vasoconstriction [ xref ]."

sparser
"This effect is mediated primarily by Akt-dependent phosphorylation of eNOS at serine 1177 xref , xref ."

sparser
"PI3K activated by the adherens junction mechanosensory complex also phosphorylates Akt, which then phosphorylates eNOS to stimulate NO release xref , xref ."

sparser
"On activation, Akt phosphorylates eNOS leading to increased nitric oxide production."

sparser
"In this example, AKT is A , PP2A is B , and eNOS is C . When active, AKT phosphorylates and activates eNOS."

reach
"These data are also consistent with prior studies showing that shear induced Akt dependent phosphorylation of NOS3 is decreased in aortae of older rats XREF_BIBR."

reach
"The ratios of phosphorylated (p-) eNOS and eNOS and p-Akt and Akt, but not p-PKA and PKA, were significantly increased in rats fed CAP compared with rats fed CTL."

reach
"To confirm that LA induced eNOS phosphorylation is mediated by Akt, HUVECs were treated with LA in the presence of MK-2206."

reach
"PKB causes direct phosphorylation of eNOS, reducing the enzyme 's Ca +2 requirement and causing increased production of NO."

sparser
"Selective inhibitors (i) of phosphodiesterase type 5 (PDE5) in men with ED and VRFs are effective in treating ED, while improving the endothelial function at the brachial arteries and reducing the biochemical measures of endothelial cell damage/dysfunction. xref xref xref xref xref xref These agents competitively inhibit cyclic guanosine 5’- monophosphate hydrolysis by PDE5, thereby fostering NO-dependent cyclic guanosine 5’- monophosphate accumulation and the consequent relaxation of vascular smooth muscle cells. xref It is suggested that the beneficial effect of PDE5i on endothelial cells is related to the stimulation of the synthesis and transcription of endothelial NO synthase mRNA and protein and to Akt-dependent eNOS phosphorylation. xref xref eNOS-derived NO plays an essential role in the mobilization and function of bone marrow-derived PGCs; xref whereas, the activation of the intracellular Akt pathway increases the number of ex vivo expanded CACs by modulating the survival and/or proliferation of freshly isolated cells. xref xref PDE5i treatment of men with ED and VRFs is associated with an increased number of circulating PGCs and ex vivo expanded CACs. xref xref "

sparser
"However, insulin has calcium-independent vasodilator actions that are mediated by a phosphatidylinositol 3-kinase-dependent mechanism involving phosphorylation of eNOS by Akt [ xref , xref ]."

reach
"Since both Akt and AMPK can phosphorylate eNOS and regulate its activity, NO becomes an important element in the cross-talk between insulin signaling and AMPK signaling for the regulation of GLUTs translocation."

reach
"Later on, a sequence of non classical, non genomic, E2 receptor membrane actions involving rapid signal-transduction pathways was detailed, including activation of phosphatidylinositol 3-kinase, protein kinase B (Akt) cascade generation and, by Galphai protein interaction, long lasting estrogen mediated eNOS phosphorylation and genomic NO production XREF_BIBR, XREF_BIBR, XREF_BIBR."

reach
"Both Akt and AMPK are capable of phosphorylating eNOS at Ser1179 XREF_BIBR, prompting us to determine whether Akt may also contribute to EPA enhanced eNOS phosphorylation."

reach
"The addition of purified hsp90 to in vitro kinase assays facilitates Akt driven phosphorylation of recombinant eNOS protein, but not a short peptide encoding the Akt phosphorylation site, suggesting that hsp90 may function as a scaffold for eNOS and Akt."

reach
"Additionally, Akt may phosphorylate vascular eNOS and consequently enhance NO production, leading to restrained platelet aggregation and TF expression [12]."

reach
"XREF_BIBR, XREF_BIBR Phosphorylation of eNOS by AKT is required for efficient production of nitric oxide."

reach
"Activation of Akt also appears to promote phosphorylation of eNOS, increase endothelial NO production and hence cell growth and migration."

reach
"Statins also increase eNOS activity by post-translational activation of the PI3K/Akt pathway as eNOS is phosphorylated by Akt [161]."

reach
"The potential involvement of AMPK or Akt in CTRP9 induced eNOS phosphorylation in vitro was examined by treating HUVECs with AMPK inhibitor Compound C or PI3-kinase inhibitor LY294002 (XREF_FIG)."

reach
"PI3-K and Akt signaling also stimulates the phosphorylation of eNOS in LECs XREF_BIBR, XREF_BIBR."

reach
"In fact, ROCK1 inhibits eNOS gene expression and inhibits AKT, which phosphorylates and activates eNOS.30, 31 The mechanisms through which Rac1 regulates ROCK1 expression levels remain to be clarified."

sparser
"Endothelial NOS is also phosphorylated by Akt and other upstream kinases (Fulton et al.,  xref )."

reach
"The activated PI-3/Akt pathway induces the phosphorylation of eNOS, transformation of L-arginine to L-citrulline, and production of NO."

sparser
"Akt can directly phosphorylate eNOS and activate the enzyme, leading to enhanced NO production."

sparser
"Akt, a serine/threonine kinase, phosphorylates eNOS thereby activating the enzyme. xref Phosphorylation of eNOS at Ser 1177 residue is a critical requirement for eNOS activation, whereas phosphorylation at Thr 495 residue leads to inactivation of the enzyme. xref Here we demonstrated that ethanol had no effect on the Akt/eNOS phosphorylation, which corroborated the observation that ethanol intake did not alter the concentration of nitrate in the rat MAB."

reach
"It also phosphorylates and activates IKK, which leads to activation of NF-κB. Endothelial nitric oxide synthase (eNOS) is also phosphorylated by Akt, thereby enhancing the production and release of nitric oxide (NO), a prominent vasodilator and anti-inflammatory molecule (Boucher et al., 2014)."

sparser
"Therefore, we investigated whether Akt-dependent phosphorylation of eNOS mediates the effects of VEGF on EC migration using a ‘scratched wound assay’, which resembles re-endothelialization processes."

sparser
"Akt induced eNOS phosphorylation at serine 1177 is an important mechanism to protect heart against IR injury ( xref ; xref )."

reach
"Both in vivo and in vitro phosphorylation of endothelial nitric oxide synthase (eNOS) by Akt were reduced by hyperglycemia and hexosamine activation."

sparser
"PECAM-1 has no mechanosensing properties, but plays an important role in the delayed Ca 2+ -independent eNOS activation in response to shear, which seems to involve Akt-dependent phosphorylation of eNOS by serine 1177, as demonstrated in PECAM-1-deficient mice ( xref , xref )."

sparser
"In ECs, Ca++ flux in response to either shear stress or a PIEZO1 agonist, Yoda, leads to cellular ATP release, followed by NO synthesis downstream of the actions of the exported ATP on purinergic receptors and endothelial NO synthase activation secondary to phosphorylation of eNOS by AKT (Wang et al., 2016)."

reach
"Statin may also induce Akt mediated phosphorylation of eNOS, although phospho-eNOS expression was not upregulated under our experimental condition."

reach
"Thus, phosphorylation of eNOS by Akt represents a novel Ca2 +-independent regulatory mechanism for activation of eNOS."

reach
"Our results suggest that fucoidan increased nitric oxide production by activating eNOS and Akt phosphorylation, which could be impaired by Akt or eNOS inhibitors."

reach
"Su and colleagues demonstrated that EPO is able to activate eNOS in endothelial cells by interacting with the betacR and causing Akt dependent phosphorylation of eNOS."

sparser
"Phosphorylation of eNOS by Akt resulted in activation, and increased production of NO. ( xref )."

sparser
"We conclude that pyridoxine is effective in ameliorating the dysfunction of platelet NO signaling in response to AGEs, through improving PI3K activity, and hence downstream Akt phosphorylation and in turn serine-1177 phosphorylation of NOS-3."

reach
"22 It is known that Akt activity enhances phosphorylation of eNOS, which is antagonized by the activation of p38 MAPK."

reach
"In addition, the peptides in the hydrolysates could have acted by inducing vasodilation as mediated by activation of Akt to phosphorylate eNOS which produced NO, a potent vasodilator as illustrated in Fig. 3 ."

sparser
"Moreover, a link between the inhibition of mTOR and the activation of eNOS had been suggested by studies showing that Akt, which phosphorylates eNOS and increases NO production, can be activated by rapamycin treatment [ xref ] and conversely, that activation of mTOR results in Akt inhibition [ xref ]."

sparser
"Among these signals, Akt-dependent eNOS phosphorylation is crucial for angiogenesis. xref "

reach
"Activated p38 MAPK induced Akt-dependent phosphorylation of eNOS at Ser1177."

reach
"ENOS is phosphorylated, and thus activated, by the serine/threonine protein kinase AKT, which is recruited to the cell membrane by PI3-kinase as an anti-apoptotic mechanism in the response of endothel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"AKT is activated by PI3K and phosphorylates eNOS to promote the synthesis and release of endogenous NO, which protects VECs."

reach
"Simvastatin induces Akt mediated phosphorylation of eNOS, which gives rise to heightened NO production and endothelial cell survival."

sparser
"Compounds such as acetylcholine (ACh) and testosterone activate eNOS via downstream phosphorylation of the serine-threonine kinase Akt which subsequently phosphorylates eNOS [ xref ]."

sparser
"Here, using a previously undescribed genetic strategy, we show that eNOS phosphorylation on the canonical Akt site, S 1176 , is critical for many of the vascular actions of Akt in vivo."

sparser
"Previous work revealed that the Akt-dependent phosphorylation of eNOS mediates penile erection xref ."

reach
"The suggested mechanism is that CR activates Akt, which directly phosphorylates eNOS activating the enzyme and leading to NO production [XREF_BIBR, XREF_BIBR - XREF_BIBR]."

reach
"For example, in endothelial cells, when PKB is activated and phosphorylates eNOS, are all other substrates of PKB being phosphorylated at the same time?"

sparser
"This was subsequently associated with a significant increase in phosphorylation of eNOS by Akt and the rescue of high glucose-impaired tubulogenesis in vitro [ xref ]."

reach
"We and others have previously demonstrated that Akt mediates eNOS phosphorylation, and subsequent NO synthesis."

reach
"PI3K and Akt signaling pathway in eNOS phosphorylation by NRR volatile oil."

reach
"Another potential mechanism is that statins increase activity of Akt/protein kinase B, which phosphorylates and activates eNOS, thereby increasing NO bioavailability [60]."

reach
"This takes place by activating the ETB receptor pathway and PI3-K and Akt, which then stimulates the phosphorylation of eNOS, to produce further NO."

sparser
"Accordingly, FTY720 induced NO release, Akt-dependent eNOS phosphorylation and activation in human endothelial cells."

reach
"Akt can directly phosphorylate eNOS and activate the enzyme, leading to enhanced NO production."

reach
"The PI3K and Akt signaling pathway can regulate eNOS activity, and activation of Akt has been reported to stimulate phosphorylation of eNOS."

sparser
"Statins also increase eNOS activity by post-translational activation of the phosphatidylinositol 3-kinase/protein kinase Akt (PI3k/Akt) pathway as eNOS is phosphorylated by Akt. xref Inhibition of the Rho/ROCK pathway activates the PI3k/Akt pathway and cardioprotection. xref , xref ROCK is a negative regulator of the Akt pathway, possibly through activation of phosphatase and tensin homologue. xref "

sparser
"Simvastatin increased eNOS expression, Akt-dependent eNOS phosphorylation and cGMP liver content."

sparser
"AKT is activated by PI3K and phosphorylates eNOS to promote the synthesis and release of endogenous NO, which protects VECs ( xref ; xref )."

reach
"Phosphorylation of NOS3 by protein kinase AKT can also increase the enzyme activity of NOS3 [XREF_BIBR]."

reach
"IRS1 activates the PI3K and Akt, which, in turn, phosphorylates eNOS at Ser1177, catalyzing the conversion of L-arginine to L-citrulline and NO [XREF_BIBR]."

reach
"The insulin mediated activation of phosphatidylinositol 3 '-kinase (PI3K) results in the activation of Akt, which on its turn promotes the phosphorylation of endothelial nitric oxide synthase (eNOS) [[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"PKB phosphorylates eNOS, increasing NO production and vasodilation, while the MAPK pathway results in endothelin-1 production and vasoconstriction [XREF_BIBR]."

reach
"Since Akt is an upstream regulator of eNOS, we next examined the hypothesis that Akt inhibition by A-443654 may reduce eNOS phosphorylation."

reach
"Finally, PKB phosphorylated eNOS in vitro at the same site phosphorylated in the cell and increased eNOS enzymatic activity by 15-20-fold."

sparser
"ROCK negatively regulates the function of endothelial nitric oxide synthase eNOS (NOS3) by inhibiting AKT phosphorylation of eNOS on Ser-1177 leading to decreased NO production (Ming et al. xref )."

sparser
"In our study, we demonstrated increased expression of phosphorylated Akt (p-Akt) and phosphorylated eNOS (p-eNOS) in the ADSC-treated group compared with those of the other groups."

reach
"We and others have demonstrated that eNOS phosphorylation in sinusoidal endothelial cells is abnormal after injury, likely due to abnormal post-translational modification (s) (XREF_FIG); for example, Akt phosphorylation and subsequent activation of eNOS enzymatic activity are reduced in injured compared to normal sinusoidal endothelial cells."

reach
"Since Akt phosphorylates and activates eNOS [XREF_BIBR], which plays a role in regulation of cell adhesion [XREF_BIBR, XREF_BIBR], we analyzed the role of Akt in regulation of eNOS coupling after UVB irradiation using a SDS resistant reducing gel [XREF_BIBR]."

reach
"Akt phosphorylation and activation of endothelial NOS (eNOS) stimulates RNS dependent oxidation or S nitrosylation of Cys 118 of Ras resulting in cytoprotective signaling through Akt."

sparser
"Akt phosphorylated only CaM-bound eNOS, in an HSP90-independent manner."

sparser
"PKB causes direct phosphorylation of eNOS, reducing the enzyme's Ca +2 requirement and causing increased production of NO."

rlimsp
"Since eNOS phosphorylation by AKT could be direct or indirect, eNOS inhibitor (1 mM NG-Monomethyl arginine, CalBiochem) was also used in this experiment as a control to test actual eNOS dependency (Figure 2)."

sparser
"Overexpression of XBP1s increases Akt phosphorylation [ xref ], whereas the phosphorylation of NOS3 by Akt represents a major Ca 2+- independent regulatory mechanism for the activation of eNOS [ xref ]."

reach
"Small-molecule Akt activation leads to eNOS phosphorylation and production of NO."
| PMC

reach
"Recent evidence demonstrated that NADPH oxidase mediated ROS regulates Akt phosphorylation and activation of eNOS [XREF_BIBR]."

reach
"Thus, phosphorylation of eNOS by Akt represents a novel Ca 2+ -dependent regulatory mechanism for activation of eNOS."

reach
"Phosphorylated eNOS and Akt levels were much lower than those in the sham group at 24h after MCAO-R, suggesting that losartan pretreatment significantly preserved eNOS phosphorylation in response to the activated Akt."

reach
"XREF_BIBR, XREF_BIBR The effects of statins on eNOS expression are not reversed by FPP or LDL-C, indicating that the effect is likely mediated through the geranylgeranylation of RhoA and ROCK signaling 80 Statins also increase eNOS activity by post-translational activation of the phosphatidylinositol 3-kinase/protein kinase Akt (PI3k and Akt) pathway as eNOS is phosphorylated by Akt."

reach
"According to a study by Sun et al. [XREF_BIBR], the Akt kinase inhibitor (GSK690693) inhibited Akt and eNOS phosphorylation, suggesting that Akt may be necessary to activate eNOS."

reach
"Furthermore, blockade of AMPK or Akt signaling pathway reversed the CTRP9 stimulated eNOS phosphorylation in HUVECs."

reach
"In the condition of fluid shear stress, phosphorylation of eNOS by Akt represents the most important pathway for eNOS activation [XREF_BIBR, XREF_BIBR]."

reach
"Compared with 18 matched control, ET in 17 stable CAD patients significantly improved endothelial function, which may be closely related to shear-stress induced phosphorylation of eNOS at Ser 1177 residue by AKT [85]."
| PMC

reach
"This Tie2-VE-PTP complex preferentially activates Akt serine kinase, which phosphorylates endothelial nitric oxide synthase (eNOS)."

reach
"Dimmeler et al. reported that NO production in response to shear stress is controlled by the Akt dependent phosphorylation of eNOS in cultured ECs XREF_BIBR."

sparser
"Akt can also phosphorylate eNOS to increase eNOS stability and coupling [ xref ]."

reach
"Akt promotes eNOS phosphorylation and activity, which is essential for EC migration, and has anti-apoptotic effects in EC XREF_BIBR, XREF_BIBR."

sparser
"Regulation of eNOS phosphorylation by Akt."

sparser
"However, this residual phosphorylation in Akt1 −/− mice was not sufficient to promote blood flow recovery and tissue healing, arguing that Akt phosphorylation of eNOS plays a critical role in adaptive angiogenesis."

reach
"Thus, we determined whether Akt also contributes to OA-NO 2 -induced eNOS phosphorylation."

reach
"In endothelial cells, stimulation of phosphatidylinositol 3 '-kinase (PI-3K) signaling activates AKt (PKB)-mediated phosphorylation of eNOS, resulting in the production of NO (Dimmeler et al. 1999; Fulton et al. 1999)."

rlimsp
"We conclude that insulin regulates eNOS activity using a Ca(2+)-independent mechanism requiring phosphorylation of eNOS by Akt."

sparser
"Biochemical approaches validate S1176 phosphorylation as the main activation site in intact cells, as a ‘loss-of-function’ mutation to alanine (S1176A) abolishes Akt-dependent eNOS phosphorylation and reduces NO release."

sparser
"In endothelial cells it is Akt-dependent eNOS phosphorylation and Cav1 expression that are most sensitive to statins effects ( xref ; xref )."

reach
"AKT can also phosphorylate eNOS and promote NO production XREF_BIBR, XREF_BIBR, enhancing blood flow, cell survival, morphogenesis, and angiogenesis, even in the setting of ischemia XREF_BIBR, XREF_BIBR."

reach
"SPP also stimulates eNOS phosphorylation and NO release and these effects are also attenuated by inhibition of G (i) signaling, PI 3-kinase, and Akt."

reach
"Although reduced Akt dependent phosphorylation of eNOS in micro- and macro-vasculature of aged animals has been demonstrated, the involvement of reduced eNOS phosphorylation in human vascular aging needs to be confirmed."

reach
"Akt can directly phosphorylate eNOS and activate it, leading to NO production."
| PMC

sparser
"Thus, simvastatin treatment of resting HUVEC results in rapid PI3K-dependent phosphorylation of the serine threonine kinase Akt and Akt-dependent phosphorylation and activation of eNOS [ xref , xref ]."

reach
"The level of phosphorylated ERK1/2, Akt, and nNOS proteins may be recovered after AZD8797 treatment, and phosphorylated eNOS protein did not show any significant difference."
| PMC

sparser
"Akt can directly phosphorylate eNOS [ xref ]."

reach
"Akt nitration can activate eNOS phosphorylation, and this, in turn, increases peroxynitrite formation, nitrosative stress, and mitochondrial dysfunction."

reach
"The underlying mechanism involves decreased eNOS interaction with its positive protein regulator HSP90, which decreases AKT activation and AKT mediated eNOS phosphorylation on this site, decreasing constitutive NOS catalytic activity."

sparser
"Fulton et al. [ xref ] and Skaletz-Rorowski et al. [ xref ] demonstrated that Akt phosphorylates eNOS, while mevalonate inhibits phosphatidylinositol-3 kinase and thereby reduces Akt activation."

reach
"Akt may phosphorylate the vascular eNOS and enhance NO production (Yang and Loscalzo, 2000)."

reach
"Hence, there is a lag between calcium and NO dynamics; this is due to the relatively slow rate at which eNOS binds with CaM and is then phosphorylated by AKT."

reach
"Our data clearly demonstrate that eNOS phosphorylation downstream of the angiogenic agonist VEGF, as well as genetic augmentation of PI3K signaling, is not mediated directly by AKT."

sparser
"Activated Akt phosphorylates eNOS, leading to the improvement of endothelial function."

sparser
"PI3K can phosphorylate the serine/threonine of its downstream signal kinase Akt, which may further phosphorylate eNOS to promote an increase in endogenous NO generation."

reach
"VEGF signaling to eNOS is principally mediated by an Akt dependent phosphorylation of eNOS and by increased association of eNOS to the molecular chaperone, heat-shock protein 90 kDa (Hsp90)."

reach
"A previous study suggested the potential role of Akt dependent signaling in the beneficial effects of TH after CA. 26 Since Akt phosphorylates NOS3, we examined expression of phosphorylated Akt in the brain of WT mice resuscitated from CA/CPR."

reach
"Using signaling pathway inhibitors, we discovered that AKT and calcium signaling contributed to eNOS phosphorylation induced by C1213."

reach
"The second is phosphorylation of eNOS by protein kinases PKC and AKT."

sparser
"As Akt phosphorylates eNOS and therefore is able to promote NO bioavailability and impact EDR in large vessels, we determined the ratio of phosphorylated to total Akt in aortas from young and old rats."

sparser
"Thus, phosphorylation of eNOS by Akt represents a novel Ca 2+ -dependent regulatory mechanism for activation of eNOS."

reach
"PI3K can phosphorylate the serine/threonine of its downstream signal kinase Akt, which may further phosphorylate eNOS to promote an increase in endogenous NO generation."

reach
"Many growth factors and hormones have been shown to induce phosphoinositide 3-kinase-Akt (PI3K-Akt)-dependent phosphorylation of eNOS, which activates NOS and induces subsequent increases in NO production XREF_BIBR, XREF_BIBR."

reach
"Recent reports (Fulton et al., 1999; Dimmeler et al., 1999) indicate that the serine/threonine protein kinase Akt and PKB, which is a downstream substrate of PI3K phosphorylates and activates eNOS, le[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Akt can also phosphorylate and activate eNOS, leading to enhanced NO production and vasodilation."

reach
"Phosphorylation of eNOS by Akt or AMPK enhances both eNOS activity and the production of NO [XREF_BIBR, XREF_BIBR], while CDK5 or ERK reduces both via phosphorylation of the Ser116 site [XREF_BIBR, XREF_BIBR]."