Phosphorylation of Tie2 by Ang1?
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Activation of the Tie2 receptor by Ang1 leads to phosphorylation of Tie2 . Ang1-induced Tie2 dimerization occurs via the formation of an intermolecular β-sheet between the membrane-proximal Fibronectin type III domains of Tie2 . The phosphorylation of Tie2 is essential for its activation and downstream signaling .
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| Ang1 induces Tie2 phosphorylation by promoting Tie2 dimerization through the formation of an intermolecular β-sheet between the Fn3 domains of Tie2. | |
9 Citations | Yes, the new soluble ANG1 mimetic, Hepta-ANG1, induces Tie2 phosphorylation in cultured cells and in the lung following intravenous injection of mice. |
| When Ang1 binds to Tie2, it leads to the auto-phosphorylation of Tie2, which promotes anti-apoptotic activity in vascular endothelial cells. |
Related Questions
How does studied phosphorylation?5 answersProtein phosphorylation is studied through various methods and approaches. One approach involves the purification and manipulation of phosphoproteins, using computational and biochemical techniques to analyze their structure and function. Another strategy combines fluorescence resonance energy transfer (FRET) with a small molecule ATP analogue to study protein phosphorylation in living cells. Phosphorylation can also be examined through PAGE electrophoresis and tandem mass spectrometry (MS/MS) to identify specific phosphorylation sites. Additionally, a novel method based on the phosphorylation-dependent electrophoretic mobility shift (PDEMS) has been developed to detect protein phosphorylation, allowing for the measurement of the ratio of protein phosphorylation in cells. These different approaches provide insights into the mechanisms and functional implications of protein phosphorylation in various cellular processes.
AMPK phosphorylation promotes ACC phosphorylation?is?5 answersAMPK phosphorylation does not appear to be essential for the phosphorylation of ACC. In a study by Zordoky et al., a double knock-in mouse model was generated to prevent AMPK-dependent inhibitory phosphorylation of ACC. Despite the inability of AMPK to regulate ACC activity, the hearts from these mice displayed normal basal AMPK activation and cardiac function, indicating that AMPK-dependent inactivation of ACC is not necessary for the control of myocardial fatty acid oxidation (FAO) and cardiac function. Another study by Janovska et al. found that leptin stimulated the phosphorylation of AMPK and ACC in lean animals, but this effect was absent in obese animals, suggesting that the effect of leptin on AMPK and ACC phosphorylation is muscle fiber type dependent and fails in diet-induced obesity. Therefore, while AMPK phosphorylation may play a role in the regulation of ACC activity, it is not essential for ACC phosphorylation.
What are the mechanisms by which ANG2 elevations lead to HHT pathologies?3 answersElevated levels of ANG2 have been implicated in various pathologies. In sepsis-associated lung injury, ANG2 disrupts endothelial barrier function, leading to vascular leak and impaired oxygenation. In chronic heart failure, ANG2 is associated with sympathoexcitation and blunted arterial baroreflex function. ANG2 also plays a role in cardiac hypertrophy, with the activation of AT1 receptors mediating physiological hypertrophy and the reduction of AT2 receptors and Mas receptors contributing to pathological hypertrophy. Additionally, ANG2 is involved in abnormal collagen deposition and altered cardiac function in hypertrophy and heart failure. In hypertension, elevated circulating levels of ANG2 can disrupt the blood-brain barrier, allowing access of ANG2 to critical sympathoexcitatory brain centers, exacerbating sympatho-humoral activation. These mechanisms collectively contribute to the pathologies associated with ANG2 elevations.
How FoxO1 regulates Ang2 expression?5 answersFoxO1 regulates Ang2 expression through the Akt/FKHR pathway, as demonstrated in the study by Daly et al.. They found that Ang-1, a regulator of vascular development, inhibits FKHR (FOXO1) through Akt activation, thereby modulating gene expression. FKHR regulates genes associated with vascular destabilization and remodeling, including Ang-2, an Ang-1 antagonist. Ang-1 inhibits FKHR-mediated changes in gene expression, including the expression of Ang-2. This study provides insight into the molecular mechanisms underlying Ang-1 function and its role in regulating endothelial cell survival and blood vessel stability.
What are the effects of phosphorylation of Tie2 on Ang1?5 answersPhosphorylation of Tie2 has been shown to have effects on Ang1 signaling. In one study, it was found that mutation in the Tie2 tyrosine 1106 residue directed endothelial progenitor cells (EPCs) towards a mature endothelial phenotype, which was associated with increased phosphorylation of the active site (tyrosine 992). Another study demonstrated that both Ang1 and Ang2 binding to Tie2 increased Tie1-Tie2 interactions in a β1 integrin-dependent manner, and Tie1 was essential for the agonist activity of Ang1. These findings suggest that phosphorylation of Tie2 may play a role in mediating the effects of Ang1 on endothelial cells and EPCs. However, further research is needed to fully understand the specific mechanisms and consequences of Tie2 phosphorylation in the context of Ang1 signaling.
What is the effect of VEGF on phosphorylation of Tie2?4 answersVEGF has been shown to regulate the phosphorylation of Tie2. It induces proteolytic cleavage and shedding of Tie2 via a PI3K/Akt-dependent pathway. VEGF treatment leads to both constitutive and inducible Tie2 shedding, which is mediated by PI3K/Akt and p38 MAPK. Overexpression of the lipid phosphatase PTEN blocks Tie2 shedding, while overexpression of dominant negative PTEN or constitutively active Akt enhances Tie2 shedding. The shedding of Tie2 by VEGF inhibits angiopoietin-Tie2 signaling, resulting in the inhibition of vascular stabilization and promotion of angiogenesis and vascular remodeling.