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Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling

Overview of attention for article published in Cancer Cell, September 2014
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (88th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (57th percentile)

Mentioned by

twitter
17 tweeters
f1000
1 research highlight platform

Citations

dimensions_citation
78 Dimensions

Readers on

mendeley
215 Mendeley
citeulike
1 CiteULike
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Title
Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling
Published in
Cancer Cell, September 2014
DOI 10.1016/j.ccr.2014.07.007
Pubmed ID
Authors

Jacob R. Haling, Jawahar Sudhamsu, Ivana Yen, Steve Sideris, Wendy Sandoval, Wilson Phung, Brandon J. Bravo, Anthony M. Giannetti, Ariana Peck, Alexandre Masselot, Tony Morales, Darin Smith, Barbara J. Brandhuber, Sarah G. Hymowitz, Shiva Malek

Abstract

Numerous oncogenic mutations occur within the BRAF kinase domain (BRAF(KD)). Here we show that stable BRAF-MEK1 complexes are enriched in BRAF(WT) and KRAS mutant (MT) cells but not in BRAF(MT) cells. The crystal structure of the BRAF(KD) in a complex with MEK1 reveals a face-to-face dimer sensitive to MEK1 phosphorylation but insensitive to BRAF dimerization. Structure-guided studies reveal that oncogenic BRAF mutations function by bypassing the requirement for BRAF dimerization for activity or weakening the interaction with MEK1. Finally, we show that conformation-specific BRAF inhibitors can sequester a dormant BRAF-MEK1 complex resulting in pathway inhibition. Taken together, these findings reveal a regulatory role for BRAF in the MAPK pathway independent of its kinase activity but dependent on interaction with MEK.

Twitter Demographics

The data shown below were collected from the profiles of 17 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 215 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Malaysia 1 <1%
Netherlands 1 <1%
France 1 <1%
Austria 1 <1%
United Kingdom 1 <1%
Canada 1 <1%
Denmark 1 <1%
Japan 1 <1%
United States 1 <1%
Other 0 0%
Unknown 206 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 72 33%
Researcher 51 24%
Student > Bachelor 24 11%
Student > Master 16 7%
Professor > Associate Professor 9 4%
Other 24 11%
Unknown 19 9%
Readers by discipline Count As %
Agricultural and Biological Sciences 72 33%
Biochemistry, Genetics and Molecular Biology 70 33%
Chemistry 23 11%
Medicine and Dentistry 17 8%
Pharmacology, Toxicology and Pharmaceutical Science 7 3%
Other 6 3%
Unknown 20 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 30 March 2016.
All research outputs
#1,525,007
of 14,765,478 outputs
Outputs from Cancer Cell
#845
of 2,327 outputs
Outputs of similar age
#22,563
of 198,548 outputs
Outputs of similar age from Cancer Cell
#19
of 45 outputs
Altmetric has tracked 14,765,478 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,327 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.0. This one has gotten more attention than average, scoring higher than 63% of its peers.
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 198,548 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 45 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.