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Essential roles of PI(3)K–p110β in cell growth, metabolism and tumorigenesis

Overview of attention for article published in Nature, June 2008
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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 (84th percentile)

Mentioned by

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7 patents
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1 research highlight platform

Citations

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506 Dimensions

Readers on

mendeley
236 Mendeley
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2 CiteULike
connotea
1 Connotea
Title
Essential roles of PI(3)K–p110β in cell growth, metabolism and tumorigenesis
Published in
Nature, June 2008
DOI 10.1038/nature07091
Pubmed ID
Authors

Shidong Jia, Zhenning Liu, Sen Zhang, Pixu Liu, Lei Zhang, Sang Hyun Lee, Jing Zhang, Sabina Signoretti, Massimo Loda, Thomas M. Roberts, Jean J. Zhao

Abstract

On activation by receptors, the ubiquitously expressed class IA isoforms (p110alpha and p110beta) of phosphatidylinositol-3-OH kinase (PI(3)K) generate lipid second messengers, which initiate multiple signal transduction cascades. Recent studies have demonstrated specific functions for p110alpha in growth factor and insulin signalling. To probe for distinct functions of p110beta, we constructed conditional knockout mice. Here we show that ablation of p110beta in the livers of the resulting mice leads to impaired insulin sensitivity and glucose homeostasis, while having little effect on phosphorylation of Akt, suggesting the involvement of a kinase-independent role of p110beta in insulin metabolic action. Using established mouse embryonic fibroblasts, we found that removal of p110beta also had little effect on Akt phosphorylation in response to stimulation by insulin and epidermal growth factor, but resulted in retarded cell proliferation. Reconstitution of p110beta-null cells with a wild-type or kinase-dead allele of p110beta demonstrated that p110beta possesses kinase-independent functions in regulating cell proliferation and trafficking. However, the kinase activity of p110beta was required for G-protein-coupled receptor signalling triggered by lysophosphatidic acid and had a function in oncogenic transformation. Most strikingly, in an animal model of prostate tumour formation induced by Pten loss, ablation of p110beta (also known as Pik3cb), but not that of p110alpha (also known as Pik3ca), impeded tumorigenesis with a concomitant diminution of Akt phosphorylation. Taken together, our findings demonstrate both kinase-dependent and kinase-independent functions for p110beta, and strongly indicate the kinase-dependent functions of p110beta as a promising target in cancer therapy.

Mendeley readers

The data shown below were compiled from readership statistics for 236 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 6 3%
United Kingdom 4 2%
New Zealand 2 <1%
Canada 1 <1%
Japan 1 <1%
Germany 1 <1%
Unknown 221 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 63 27%
Researcher 59 25%
Professor > Associate Professor 21 9%
Student > Master 20 8%
Other 15 6%
Other 43 18%
Unknown 15 6%
Readers by discipline Count As %
Agricultural and Biological Sciences 109 46%
Biochemistry, Genetics and Molecular Biology 49 21%
Medicine and Dentistry 27 11%
Chemistry 13 6%
Immunology and Microbiology 3 1%
Other 13 6%
Unknown 22 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 02 October 2018.
All research outputs
#2,216,959
of 13,583,786 outputs
Outputs from Nature
#39,128
of 70,046 outputs
Outputs of similar age
#30,515
of 210,402 outputs
Outputs of similar age from Nature
#758
of 1,050 outputs
Altmetric has tracked 13,583,786 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 70,046 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 76.7. This one is in the 43rd percentile – i.e., 43% 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 210,402 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 84% of its contemporaries.
We're also able to compare this research output to 1,050 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.