Evidence map›Paper›PMID 25043303›Full record

ArticleOncogene2015

Phosphorylation of Dok1 by Abl family kinases inhibits CrkI transforming activity.

K Y Ng, T Yin, K Machida, Y I Wu, B J Mayer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. CD200-CD200R signaling and diseases: a potential therapeutic target?International journal of physiology, pathophysiology and pharmacology · 2019
    Review
  5. 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

5 authors at 1 institution in 1 country.

K Y NgRaymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA.
T YinRichard D. Berlin Center for Cell Analysis and Modeling, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA.
K MachidaRaymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA.
Y I WuRichard D. Berlin Center for Cell Analysis and Modeling, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA.
B J Mayer1] Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA [2] Richard D. Berlin Center for Cell Analysis and Modeling, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA.
UConn Health · US

Funding

Functional Role of NCK and CRK Binding InteractionsR01CA082258 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI MAYER, BRUCE J. · 1999 to 2012
$4.2M
Engineering a new class of optogenetic tools targeting small GTPases and kinasesR21NS071216 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WU, YI · 2010 to 2011
$411k
NCI NIH HHS CA82258NCI NIH HHS R01 CA082258NINDS NIH HHS NS071216NINDS NIH HHS R21 NS071216
6 · The paper itself

Abstract

The Crk SH2/SH3 adaptor and the Abl nonreceptor tyrosine kinase were first identified as oncoproteins, and both can induce tumorigenesis when overexpressed or mutationally activated. We previously reported the surprising finding that inhibition or knockdown of Abl family kinases enhanced transformation of mouse fibroblasts by CrkI. Abl family inhibitors are currently used or are being tested for treatment of human malignancies, and our finding raised concerns that such inhibitors might actually promote the growth of tumors overexpressing CrkI. Here, we identify the Dok1 adaptor as the key effector for the enhancement of CrkI transformation by Abl inhibition. We show that phosphorylation of tyrosines 295 and 361 of Dok1 by Abl family kinases suppresses CrkI transforming activity, and that upon phosphorylation these tyrosines bind the SH2 domains of the Ras inhibitor p120 RasGAP. Knockdown of RasGAP resulted in a similar enhancement of CrkI transformation, consistent with a critical role for Ras activity. Imaging studies using a FRET sensor of Ras activation revealed alterations in the localization of activated Ras in CrkI-transformed cells. Our results support a model in which Dok1 phosphorylation normally suppresses localized Ras pathway activity in Crk-transformed cells via recruitment and/or activation of RasGAP, and that preventing this negative feedback mechanism by inhibiting Abl family kinases leads to enhanced transformation by Crk.

Indexed as

AnimalsCell Transformation, NeoplasticDNA-Binding ProteinsHumansMiceNeoplasmsNIH 3T3 Cellsp120 GTPase Activating ProteinPhosphoproteinsPhosphorylationProtein Kinase InhibitorsProto-Oncogene Proteins c-ablProto-Oncogene Proteins c-crkras ProteinsRNA-Binding ProteinsDNA-Binding ProteinsDok1 protein, mousep120 GTPase Activating ProteinPhosphoproteinsProtein Kinase InhibitorsProto-Oncogene Proteins c-ablProto-Oncogene Proteins c-crkras ProteinsRNA-Binding Proteins

Identifiers

PMID25043303
PMCPMC4302068
OpenAlexW2057204342

What OpenQuestion holds

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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.