↓ Skip to main content

Expression and Characterization of GSK-3 Mutants and Their Effect on β-Catenin Phosphorylation in Intact Cells*

Overview of attention for article published in Journal of Biological Chemistry, April 2002
Altmetric Badge

Mentioned by

patent
15 patents

Citations

dimensions_citation
86 Dimensions

Readers on

mendeley
58 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Expression and Characterization of GSK-3 Mutants and Their Effect on β-Catenin Phosphorylation in Intact Cells*
Published in
Journal of Biological Chemistry, April 2002
DOI 10.1074/jbc.m201364200
Pubmed ID
Authors

Thilo Hagen, Elena Di Daniel, Ainsley A. Culbert, Alastair D. Reith

Abstract

Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase that is involved in multiple cellular signaling pathways, including the Wnt signaling cascade where it phosphorylates beta-catenin, thus targeting it for proteasome-mediated degradation. Unlike phosphorylation of glycogen synthase, phosphorylation of beta-catenin by GSK-3 does not require priming in vitro, i.e. it is not dependent on the presence of a phosphoserine, four residues C-terminal to the GSK-3 phosphorylation site. Recently, a means of dissecting GSK-3 activity toward primed and non-primed substrates has been made possible by identification of the R96A mutant of GSK-3beta. This mutant is unable to phosphorylate primed but can still phosphorylate unprimed substrates (Frame, S., Cohen, P., and Biondi R. M. (2001) Mol. Cell 7, 1321-1327). Here we have investigated whether phosphorylation of Ser(33), Ser(37), and Thr(41) in beta-catenin requires priming through prior phosphorylation at Ser(45) in intact cells. We have shown that the Arg(96) mutant does not induce beta-catenin degradation but instead stabilizes beta-catenin, indicating that it is unable to phosphorylate beta-catenin in intact cells. Furthermore, if Ser(45) in beta-catenin is mutated to Ala, beta-catenin is markedly stabilized, and phosphorylation of Ser(33), Ser(37), and Thr(41) in beta-catenin by wild type GSK-3beta is prevented in intact cells. In addition, we have shown that the L128A mutant, which is deficient in phosphorylating Axin in vitro, is still able to phosphorylate beta-catenin in intact cells although it has reduced activity. Mutation of Tyr(216) to Phe markedly reduces the ability of GSK-3beta to phosphorylate and down-regulate beta-catenin. In conclusion, we have found that the Arg(96) mutant has a dominant-negative effect on GSK-3beta-dependent phosphorylation of beta-catenin and that targeting of beta-catenin for degradation requires prior priming through phosphorylation of Ser(45).

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 58 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 58 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 24%
Researcher 10 17%
Student > Doctoral Student 5 9%
Student > Postgraduate 5 9%
Student > Bachelor 4 7%
Other 14 24%
Unknown 6 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 17 29%
Biochemistry, Genetics and Molecular Biology 14 24%
Medicine and Dentistry 7 12%
Neuroscience 5 9%
Chemistry 3 5%
Other 6 10%
Unknown 6 10%
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 27 February 2024.
All research outputs
#8,534,976
of 25,373,627 outputs
Outputs from Journal of Biological Chemistry
#32,956
of 85,238 outputs
Outputs of similar age
#43,086
of 127,905 outputs
Outputs of similar age from Journal of Biological Chemistry
#374
of 848 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 85,238 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 15th percentile – i.e., 15% 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 127,905 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 5th percentile – i.e., 5% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 848 others from the same source and published within six weeks on either side of this one. This one is in the 5th percentile – i.e., 5% of its contemporaries scored the same or lower than it.