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Common Polymorphism in the Phosphatase PHLPP2 Results in Reduced Regulation of Akt and Protein Kinase C*

Overview of attention for article published in Journal of Biological Chemistry, March 2009
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Citations

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33 Mendeley
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Title
Common Polymorphism in the Phosphatase PHLPP2 Results in Reduced Regulation of Akt and Protein Kinase C*
Published in
Journal of Biological Chemistry, March 2009
DOI 10.1074/jbc.m901468200
Pubmed ID
Authors

John Brognard, Matthew Niederst, Gloria Reyes, Noel Warfel, Alexandra C. Newton

Abstract

PHLPP2 (PH domain leucine-rich repeat protein phosphatase 2) terminates Akt and protein kinase C (PKC) activity by specifically dephosphorylating these kinases at a key regulatory site, the hydrophobic motif (Ser-473 in Akt1). Here we identify a polymorphism that results in an amino acid change from a Leu to Ser at codon 1016 in the phosphatase domain of PHLPP2, which reduces phosphatase activity toward Akt both in vitro and in cells, in turn resulting in reduced apoptosis. Depletion of endogenous PHLPP2 variants in breast cancer cells revealed the Ser-1016 variant is less functional toward both Akt and PKC. In pair-matched high grade breast cancer samples we observed retention of only the Ser allele from heterozygous patients (identical results were observed in a pair-matched normal and tumor cell line). Thus, we have identified a functional polymorphism that impairs the activity of PHLPP2 and correlates with elevated Akt phosphorylation and increased PKC levels.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 18%
Student > Ph. D. Student 6 18%
Other 5 15%
Researcher 5 15%
Professor 3 9%
Other 4 12%
Unknown 4 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 14 42%
Biochemistry, Genetics and Molecular Biology 5 15%
Medicine and Dentistry 5 15%
Immunology and Microbiology 2 6%
Neuroscience 1 3%
Other 0 0%
Unknown 6 18%
Attention Score in Context

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 01 June 2009.
All research outputs
#17,286,379
of 25,374,647 outputs
Outputs from Journal of Biological Chemistry
#76,082
of 85,241 outputs
Outputs of similar age
#91,422
of 106,835 outputs
Outputs of similar age from Journal of Biological Chemistry
#357
of 394 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 85,241 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 7th percentile – i.e., 7% of its peers scored the same or lower than it.
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We're also able to compare this research output to 394 others from the same source and published within six weeks on either side of this one. This one is in the 2nd percentile – i.e., 2% of its contemporaries scored the same or lower than it.