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Quantitative analysis of insulin-like growth factor 2 receptor and insulin-like growth factor binding proteins to identify control mechanisms for insulin-like growth factor 1 receptor phosphorylation

Overview of attention for article published in BMC Systems Biology, February 2016
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2 tweeters

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Title
Quantitative analysis of insulin-like growth factor 2 receptor and insulin-like growth factor binding proteins to identify control mechanisms for insulin-like growth factor 1 receptor phosphorylation
Published in
BMC Systems Biology, February 2016
DOI 10.1186/s12918-016-0263-6
Pubmed ID
Authors

Dan Tian, Isaiah Mitchell, Pamela K. Kreeger

Abstract

The insulin-like growth factor (IGF) system impacts cellular development by regulating proliferation, differentiation, and apoptosis, and is an attractive therapeutic target in cancer. The IGF system is complex, with two ligands (IGF1, IGF2), two receptors (IGF1R, IGF2R), and at least six high affinity IGF-binding proteins (IGFBPs) that regulate IGF ligand bioavailability. While the individual components of the IGF system are well studied, the question of how these different components integrate as a system to regulate cell behavior is less clear. To analyze the relative importance of different mechanisms that control IGF network activity, we developed a mass-action kinetic model incorporating cell surface binding, phosphorylation, and intracellular trafficking events. The model was calibrated and validated using experimental data collected from OVCAR5, an immortalized ovarian cancer cell line. We then performed model analysis to examine the ability of IGF2R or IGFBPs to counteract phosphorylation of IGF1R, a critical step for IGF network activation. This analysis suggested that IGF2R levels would need to be 320-fold greater than IGF1R in order to decrease pIGF1R by 25 %, while IGFBP levels would need to be 390-fold greater. Analysis of The Cancer Genome Atlas (TCGA) data set suggested that this level of overexpression is unlikely for IGF2R in ovarian, breast, and colon cancer. In contrast, IGFBPs can likely reach these levels, suggesting that IGFBPs are the more critical regulator of IGF1R network activity. Levels of phosphorylated IGF1R were insensitive to changes in parameters regulating the IGF2R arm of the network. Using a mass-action kinetic model, we determined that IGF2R plays a minor role in regulating the activity of IGF1R under a variety of conditions and that due to their high expression levels, IGFBPs are the dominant mechanism to regulating IGF network activation.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 3%
Unknown 30 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 29%
Researcher 4 13%
Student > Bachelor 3 10%
Student > Master 2 6%
Lecturer 2 6%
Other 4 13%
Unknown 7 23%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 26%
Biochemistry, Genetics and Molecular Biology 6 19%
Medicine and Dentistry 5 16%
Economics, Econometrics and Finance 1 3%
Neuroscience 1 3%
Other 1 3%
Unknown 9 29%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 February 2016.
All research outputs
#3,622,995
of 7,182,236 outputs
Outputs from BMC Systems Biology
#433
of 797 outputs
Outputs of similar age
#168,578
of 320,133 outputs
Outputs of similar age from BMC Systems Biology
#21
of 28 outputs
Altmetric has tracked 7,182,236 research outputs across all sources so far. This one is in the 28th percentile – i.e., 28% of other outputs scored the same or lower than it.
So far Altmetric has tracked 797 research outputs from this source. They receive a mean Attention Score of 3.2. This one is in the 33rd percentile – i.e., 33% 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 320,133 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.