Evidence map›Paper›PMID 19956600›Full record

ArticlePloS one2009

Structural diversity of the active N-terminal kinase domain of p90 ribosomal S6 kinase 2.

Margarita Malakhova, Igor Kurinov, Kangdong Liu, Duo Zheng, Igor D'Angelo, Jung-Hyun Shim, Valerie Steinman, Ann M Bode, Zigang Dong

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

22 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. RiSKs in Computational Modeling of Isoform-Selective RSK Inhibitors.Journal of chemical information and modeling · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. RSK2 phosphorylates T-bet to attenuate colon cancer metastasis and growth.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  12. Article
  13. Article
  14. Article
  15. Myricetin exerts anti-proliferative, anti-invasive, and pro-apoptotic effects on esophageal carcinoma EC9706 and KYSE30 cells via RSK2.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
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

9 authors at 5 institutions in 2 countries.

Margarita MalakhovaDepartment of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.
Igor Kurinov
Kangdong Liu
Duo Zheng
Igor D'Angelo
Jung-Hyun Shim
Valerie Steinman
Ann M Bode
Zigang Dong
Hormel (United States) · USUniversity of Minnesota · USCanadian Light Source (Canada) · CACollege of Saint Benedict and Saint John's University · USCornell University · US

Funding

VITAMIN A, AND ITS PRECURSORS AND DERIVATIVES AS THERAPEUTIC MODALITIESP01CA027502 · NCI · UNIVERSITY OF ARIZONA · PI EINSPAHR, JANINE G · 1985 to 2015
$36.3M
Ultraviolet-Induced Signal TrasductionR01CA077646 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI DONG, ZIGANG · 1999 to 2010
$2.3M
The role of histone phosphorylation in arsenic-induced cell transformation and skR01ES016548 · NIEHS · UNIVERSITY OF MINNESOTA · PI DONG, ZIGANG · 2008 to 2012
$1.7M
Inhibition of Carcinogenesis by Tea and Tea ConstituentsR01CA120388 · NCI · UNIVERSITY OF MINNESOTA · PI DONG, ZIGANG · 2006 to 2010
$1.3M
NCI NIH HHS CA027502NCI NIH HHS CA077646NCI NIH HHS CA120388NCI NIH HHS P01 CA027502NCI NIH HHS R01 CA077646NCI NIH HHS R01 CA120388NCI NIH HHS R37CA08164NIEHS NIH HHS ES016548NIEHS NIH HHS R01 ES016548
6 · The paper itself

Abstract

The p90 ribosomal protein kinase 2 (RSK2) is a highly expressed Ser/Thr kinase activated by growth factors and is involved in cancer cell proliferation and tumor promoter-induced cell transformation. RSK2 possesses two non-identical kinase domains, and the structure of its N-terminal domain (NTD), which is responsible for phosphorylation of a variety of substrates, is unknown. The crystal structure of the NTD RSK2 was determined at 1.8 A resolution in complex with AMP-PNP. The N-terminal kinase domain adopted a unique active conformation showing a significant structural diversity of the kinase domain compared to other kinases. The NTD RSK2 possesses a three-stranded betaB-sheet inserted in the N-terminal lobe, resulting in displacement of the alphaC-helix and disruption of the Lys-Glu interaction, classifying the kinase conformation as inactive. The purified protein was phosphorylated at Ser227 in the T-activation loop and exhibited in vitro kinase activity. A key characteristic is the appearance of a new contact between Lys216 (betaB-sheet) and the beta-phosphate of AMP-PNP. Mutation of this lysine to alanine impaired both NTDs in vitro and full length RSK2 ex vivo activity, emphasizing the importance of this interaction. Even though the N-terminal lobe undergoes structural re-arrangement, it possesses an intact hydrophobic groove formed between the alphaC-helix, the beta4-strand, and the betaB-sheet junction, which is occupied by the N-terminal tail. The presence of a unique betaB-sheet insert in the N-lobe suggests a different type of activation mechanism for RSK2.

Indexed as

Adenosine TriphosphateAnimalsBinding SitesCrystallography, X-RayEscherichia coliGlutamic AcidLysineMiceMolecular ConformationMutationPhosphorylationProtein ConformationProtein Structure, SecondaryProtein Structure, TertiaryRibosomal Protein S6 Kinases, 90-kDaAdenosine TriphosphateGlutamic AcidLysineribosomal protein S6 kinase, 90kDa, polypeptide 3Ribosomal Protein S6 Kinases, 90-kDa

Identifiers

PMID19956600
PMCPMC2779450
OpenAlexW2106971217

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Registered trials

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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.