Rationale: Activation of Nox1 initiates redox-dependent signaling events crucial in the pathogenesis of vascular disease. Selective targeting of Nox1 is an attractive potential therapy but requires a better understanding of the molecular modifications controlling its activation. Objective: To determine the whether posttranslational modifications of Nox1 regulate its activity in vascular cells. Methods and Results: We first found evidence that Nox1 is phosphorylated in multiple models of vascular disease. Next, studies using mass spectroscopy and a pharmacological inhibitor demonstrated that protein kinase C-beta1 (PKC-βI) mediates phosphorylation of Nox1 in response to tumor necrosis factor-α (TNF-α). siRNA-mediated silencing of PKC-βI abolished TNF-α-mediated reactive oxygen species (ROS) production and vascular smooth muscle cell (VSMC) migration. Site-directed mutagenesis and isothermal titration calorimetry indicated that PKC-βI phosphorylates Nox1 at T429. Moreover, Nox1 T429 phosphorylation facilitated the association of Nox1 with the NoxA1 activation domain and was necessary for NADPH oxidase complex assembly, ROS production, and VSMC migration. Conclusions: We conclude that PKC-βI phosphorylation of T429 regulates activation of Nox1 NADPH oxidase.
Pharmacology, Toxicology and Pharmaceutical Science
2
6%
Medicine and Dentistry
2
6%
Environmental Science
1
3%
Other
4
12%
Unknown
16
48%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 November 2014.
All research outputs
#14,534,821
of 25,371,288 outputs
Outputs from Circulation Research
#5,767
of 7,667 outputs
Outputs of similar age
#116,247
of 246,373 outputs
Outputs of similar age from Circulation Research
#30
of 70 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,667 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.6. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 246,373 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 70 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.
