Evidence map›Paper›PMID 15988018›Full record

ArticleMolecular and cellular biology2005

Activation of a nuclear Cdc2-related kinase within a mitogen-activated protein kinase-like TDY motif by autophosphorylation and cyclin-dependent protein kinase-activating kinase.

Zheng Fu, Melanie J Schroeder, Jeffrey Shabanowitz, Philipp Kaldis, Kasumi Togawa, Anil K Rustgi, Donald F Hunt, Thomas W Sturgill

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

46 citing papers in PubMed, 72 citations in OpenAlex.

  1. CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026
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  11. Review
  12. Article
  13. Modulation of Primary Cilia by Alvocidib Inhibition of CILK1.International journal of molecular sciences · 2022
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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 4 institutions in 2 countries.

Zheng FuDepartment of Pharmacology and Internal Medicine, University of Virginia School, 1300 Jefferson Park Avenue, Charlottesville, Virginia 22908-0735, USA.
Melanie J Schroeder
Jeffrey Shabanowitz
Philipp Kaldis
Kasumi Togawa
Anil K Rustgi
Donald F Hunt
Thomas W Sturgill
Cancer Genetics (United States) · USDivision of Chemistry · USCancer Institute (WIA) · INNational Cancer Institute · US

Funding

PROTEIN SEQUENCING BY TANDEM MASS SPECTROMETRYR01GM037537 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HUNT, DONALD F · 1987 to 2023
$17.8M
Regulation of the cell cycle by cyclin-dependent kinasesZ01SC010367 · SC · CLINICAL SCIENCES · PI KALDIS, PHILIPP · 2001 to 2007
$1.2M
Regulation and Function of MAPKAP KinasesR01GM062890 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI STURGILL, THOMAS W · 2002 to 2005
$1.2M
NIGMS NIH HHS GM37537NIGMS NIH HHS GM62890NIGMS NIH HHS R01 GM037537NIGMS NIH HHS R01 GM062890
6 · The paper itself

Abstract

Male germ cell-associated kinase (MAK) and intestinal cell kinase (ICK) are nuclear Cdc2-related kinases with nearly identical N-terminal catalytic domains and more divergent C-terminal noncatalytic domains. The catalytic domain is also related to mitogen-activated protein kinases (MAPKs) and contains a corresponding TDY motif. Nuclear localization of ICK requires subdomain XI and interactions of the conserved Arg-272, but not kinase activity or, surprisingly, any of the noncatalytic domain. Further, nuclear localization of ICK is required for its activation. ICK is activated by dual phosphorylation of the TDY motif. Phosphorylation of Tyr-159 in the TDY motif requires ICK autokinase activity but confers only basal kinase activity. Full activation requires additional phosphorylation of Thr-157 in the TDY motif. Coexpression of ICK with constitutively active MEK1 or MEK5 fails to increase ICK phosphorylation or activity, suggesting that MEKs are not involved. ICK and MAK are related to Ime2p in budding yeast, and cyclin-dependent protein kinase-activating kinase Cak1p has been placed genetically upstream of Ime2p. Recombinant Cak1p phosphorylates Thr-157 in the TDY motif of recombinant ICK and activates its activity in vitro. Coexpression of ICK with wild-type CAK1 but not kinase-inactive CAK1 in cells also increases ICK phosphorylation and activity. Our studies establish ICK as the prototype for a new group of MAPK-like kinases requiring dual phosphorylation at TDY motifs.

Indexed as

Amino Acid MotifsAmino Acid SequenceAnimalsCatalytic DomainCDC2-CDC28 KinasesCell NucleusCells, CulturedCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesEnzyme ActivationHumansMiceMolecular Sequence DataPhosphorylationProtein Serine-Threonine KinasesProtein Structure, TertiaryCDC2-CDC28 KinasesCILK1 protein, humanCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesProtein Serine-Threonine Kinases

Identifiers

PMID15988018
PMCPMC1168834
OpenAlexW2164333292

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.