Evidence map›Paper›PMID 19470470›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2009

RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility.

Michelle D Larrea, Feng Hong, Seth A Wander, Thiago G da Silva, David Helfman, Deborah Lannigan, Jeffrey A Smith, Joyce M Slingerland

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 144 citations in OpenAlex.

  1. Review
  2. Article
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  4. Review
  5. Article
  6. Article
  7. p27, The Cell Cycle and Alzheimer´s Disease.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Article
  10. p27Cells · 2021
    Review
  11. Review
  12. Article
  13. Regulation of p27Biomolecules · 2020
    Review
  14. Article
  15. Article
  16. Article
  17. Regioselective Synthesis of aOrganic letters · 2020
    Article
  18. Article
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  20. p27 transcriptionally coregulates cJun to drive programs of tumor progression.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Michelle D LarreaDepartment of Biochemistry and Molecular Biology, Braman Family Breast Cancer Institute, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.
Feng Hong
Seth A Wander
Thiago G da Silva
David Helfman
Deborah Lannigan
Jeffrey A Smith
Joyce M Slingerland
Cancer Institute (WIA) · INUniversity of Virginia · USSylvester Comprehensive Cancer Center · US

Funding

PI3K opposes p27 and G1 arrest by TGF-B in human cancerR01CA105118 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SLINGERLAND, JOYCE MARIE · 2004 to 2014
$2.1M
The involvement of p90-RSK in the deregulation of p27F31CA113284 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LARREA, MICHELLE D · 2004 to 2007
$121k
NCI NIH HHS 1R01CA105118-01NCI NIH HHS 5F31CA113284NCI NIH HHS F31 CA113284NCI NIH HHS R01 CA105118
6 · The paper itself

Abstract

p90 ribosomal S6 kinase (RSK1) is an effector of both Ras/MEK/MAPK and PI3K/PDK1 pathways. We present evidence that RSK1 drives p27 phosphorylation at T198 to increase RhoA-p27 binding and cell motility. RSK1 activation and p27pT198 both increase in early G(1). As for many kinase-substrate pairs, cellular RSK1 coprecipitates with p27. siRNA to RSK1 and RSK1 inhibition both rapidly reduce cellular p27pT198. RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability. Moreover, RSK1 transfectants show mislocalization of p27 to cytoplasm, increased motility, and reduced RhoA-GTP, phospho-cofilin, and actin stress fibers, all of which were reversed by shRNA to p27. Phosphorylation by RSK1 increased p27pT198 binding to RhoA in vitro, whereas p27T157A/T198A bound poorly to RhoA compared with WTp27 in cells. Coprecipitation of cellular p27-RhoA was increased in cells with constitutive PI3K activation and increased in early G(1). Thus T198 phosphorylation not only stabilizes p27 and mislocalizes p27 to the cytoplasm but also promotes RhoA-p27 interaction and RhoA pathway inhibition. These data link p27 phosphorylation at T198 and cell motility. As for other PI3K effectors, RSK1 phosphorylates p27 at T198. Because RSK1 is also activated by MAPK, the increased cell motility and metastatic potential of cancer cells with PI3K and/or MAPK pathway activation may result in part from RSK1 activation, leading to accumulation of p27T198 in the cytoplasm, p27:RhoA binding, inhibition of RhoA/Rock pathway activation, and loss of actomyosin stability.

Indexed as

Cell MovementActinsCell Line, TumorCyclin-Dependent Kinase Inhibitor p27CytoplasmG1 PhaseHumansIntracellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemPhosphorylationrhoA GTP-Binding ProteinRibosomal Protein S6 Kinases, 90-kDaSignal TransductionActinsCDKN1B protein, humanCyclin-Dependent Kinase Inhibitor p27Intracellular Signaling Peptides and ProteinsrhoA GTP-Binding ProteinRHOA protein, humanRibosomal Protein S6 Kinases, 90-kDaRPS6KA1 protein, human

Identifiers

PMID19470470
PMCPMC2695095
OpenAlexW2066700256

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.