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ANGPT2 MTOR (1 - 3 of 3)
PMID: 15837070
mTOR: a placental growth signaling sensor.
Ang-2 activated mTOR via ...   (details)

ANGPT2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 15837070

mTOR: a placental growth signaling sensor.
Source

Placenta (April 2005)

Abstract

mTOR: a placental growth signaling sensor. The proliferation and differentiation of trophoblast cells is under the control of a variety of hormones and growth factors and is influenced by nutrient availability. The intracellular signaling pathways acting downstream of these mitogenic factors and nutrients to regulate trophoblast proliferation and placental development are poorly understood. Immortalized human trophoblast cells were used (HTR-8/SVneo) to investigate trophoblast proliferation in response to angiopoietin-2 (Ang-2), a major angiogenic factor and glucose (a major nutrient). Trophoblast cell proliferation was induced through activation of the phosphatidylinositol-3 (PI-3) kinase and the mammalian target of rapamycin (mTOR) signaling pathways, following Tie-2 receptor activation. Glucose also stimulated trophoblast cell proliferation through mTOR signaling. Ang-2 activated mTOR via PI-3 kinase-dependent signaling; whereas glucose-mediated mTOR activation was PI-3 kinase-independent and involved a novel nutrient sensor, glutamine fructose-6-phosphate amidotransferase (GFAT). Metabolites of the GFAT reaction acted upstream of mTOR and functioned as a nutrient sensor to regulate trophoblast cell proliferation in response to glucose. Overall, the results show that growth factor and nutrient signaling converge at tuberin, an upstream regulator of mTOR and that mTOR functions as an important placental growth signaling sensor. These results are the first to link mTOR with GFAT metabolites as nutrient sensors for trophoblast cell proliferation.

PMID: 17219409
ANG II-stimulated DNA synthesis is mediated by ANG II receptor-dependent Ca(2+)/PKC as well as EGF receptor-dependent PI3K/Akt/mTOR/p70S6K1 signal pathways in mouse embryonic stem cells.
ANG II phosphorylated ... and increased Akt, mTOR, ...   (details)

ANGPT2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 17219409

ANG II-stimulated DNA synthesis is mediated by ANG II receptor-dependent Ca(2+)/PKC as well as EGF receptor-dependent PI3K/Akt/mTOR/p70S6K1 signal pathways in mouse embryonic stem cells.
Source

Journal of cellular physiology (June 2007)

Abstract

ANG II-stimulated DNA synthesis is mediated by ANG II receptor-dependent Ca (2+) /PKC as well as EGF receptor-dependent PI3K/Akt/mTOR/p70S6K1 signal pathways in mouse embryonic stem cells. Effect of angiotensin II (ANG II) on mouse embryonic stem (ES) cell proliferation was examined. ANG II increased [(3) H] thymidine incorporation in a time- (> 4 h) and dose- (> 10 (-9) M) dependent manner. The ANG II-induced increase in [(3) H] thymidine incorporation was blocked by inhibition of ANG II type 1 (AT (1)) receptor but not by ANG II type 2 (AT (2)) receptor, and AT (1) receptor was expressed. ANG II increased inositol phosphates formation and [Ca (2+)] (i), and translocated PKC alpha, delta, and zeta to the membrane fraction. Consequently, the inhibition of PLC/PKC suppressed ANG II-induced increase in [(3) H] thymidine incorporation. The inhibition of EGF receptor kinase or tyrosine kinase prevented ANG II-induced increase in [(3) H] thymidine incorporation. ANG II phosphorylated EGF receptor and increased Akt, mTOR, and p70S6K1 phosphorylation blocked by AG 1478 (EGF receptor kinase blocker). ANG II-induced increase in [(3) H] thymidine incorporation was blocked by the inhibition of p44/42 MAPKs but not by p38 MAPK inhibition. Indeed, ANG II phosphorylated p44/42 MAPKs, which was prevented by the inhibition of the PKC and AT (1) receptor. ANG II increased c-fos, c-jun, and c-myc levels. ANG II also increased the protein levels of cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK4 but decreased the p21 (cip1/waf1) and p27 (kip1), CDK inhibitory proteins. These proteins were blocked by the inhibition of AT (1) receptor, PLC/PKC, p44/42 MAPKs, EGF receptor, or tyrosine kinase. In conclusion, ANG II-stimulated DNA synthesis is mediated by ANG II receptor-dependent Ca (2+) /PKC and EGF receptor-dependent PI3K/Akt/mTOR/p70S6K1 signal pathways in mouse ES cells.

PMID: 22028412
Activation of mTOR/p70S6 kinase by ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation.
... that activation of mTOR/p70S6K by ANG II in ...   (details)

ANGPT2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 22028412

Activation of mTOR/p70S6 kinase by ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation.
Source

American journal of physiology. Endocrinology and metabolism (1/15/2012)

Abstract

Activation of mTOR/p70S6 kinase by ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation. Elevated tissue levels of angiotensin II (ANG II) are associated with impairment of insulin actions in metabolic and cardiovascular tissues. ANG II-stimulated activation of mammalian target of rapamycin (mTOR) /p70 S6 kinase (p70S6K) in cardiovascular tissues is implicated in cardiac hypertrophy and vascular remodeling. However, the role of ANG II-stimulated mTOR/p70S6K in vascular endothelium is poorly understood. In the present study, we observed that ANG II stimulated p70S6K in bovine aortic endothelial cells. ANG II increased phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser (636/639) and inhibited the insulin-stimulated phosphorylation of endothelial nitric oxide synthase (eNOS). An inhibitor of mTOR, rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 (Ser (636/639)) and blocked the ability of ANG II to impair insulin-stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation. Moreover, point mutations of IRS-1 at Ser (636/639) to Ala prevented the ANG II-mediated inhibition of insulin signaling. From these results, we conclude that activation of mTOR/p70S6K by ANG II in vascular endothelium may contribute to impairment of insulin-stimulated vasodilation through phosphorylation of IRS-1 at Ser (636/639). This ANG II-mediated impairment of vascular actions of insulin may help explain the role of ANG II as a link between insulin resistance and hypertension.