Evidence map›Paper›PMID 9111309›Full record

ArticleMolecular and cellular biology1997

Rapid phosphorylation of Ets-2 accompanies mitogen-activated protein kinase activation and the induction of heparin-binding epidermal growth factor gene expression by oncogenic Raf-1.

S A McCarthy, D Chen, B S Yang, J J Garcia Ramirez, H Cherwinski, X R Chen, M Klagsbrun, C A Hauser, M C Ostrowski, M McMahon

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing 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

66 citing papers in PubMed, 161 citations in OpenAlex.

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  8. Mapping the molecular determinants of BRAF oncogene dependence in human lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2014
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6 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

10 authors at 3 institutions in 3 countries.

S A McCarthyDepartment of Cell Signaling, DNAX Research Institute, Palo Alto, California 94304, USA.
D Chen
B S Yang
J J Garcia Ramirez
H Cherwinski
X R Chen
M Klagsbrun
C A Hauser
M C Ostrowski
M McMahon
Toxicologie, Pharmacologie et Signalisation Cellulaire · FRBoston Children's Hospital · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

RAS ONCOGENE-ACTIVATED GENE EXPRESSIONR01CA053271 · NCI · OHIO STATE UNIVERSITY · PI OSTROWSKI, MICHAEL C. · 1991 to 2011
$2.9M
RAS INDUCED GENE EXPRESSION AND MALIGNANT TRANSFORMATIONR01CA063130 · NCI · BURNHAM INSTITUTE FOR MEDICAL RESEARCH · PI HAUSER, CRAIG A · 1995 to 2002
$958k
NCI NIH HHS CA53271NCI NIH HHS CA63130
6 · The paper itself

Abstract

Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3T3 cells transformed by oncogenic Ras and Raf and mediates the autocrine activation of the c-Jun N-terminal kinases (JNKs) observed in these cells. A 1.7-kb fragment of the promoter of the murine HB-EGF gene linked to a luciferase reporter was strongly induced following activation of deltaRaf-1:ER, a conditionally active form of oncogenic human Raf-1. Promoter activation by deltaRaf-1:ER required a composite AP-1/Ets transcription factor binding site located between bp -974 and -988 upstream of the translation initiation site. In vivo genomic footprinting indicated that the basal level of occupancy of this composite AP-1/Ets element increased following deltaRaf-1:ER activation. Cotransfection of Ets-2 and p44 mitogen-activated protein (MAP) kinase expression vectors strongly potentiated HB-EGF promoter activation in response to deltaRaf-1:ER. Potentiated activation required both p44 MAP kinase catalytic activity and threonine 72 in the Pointed domain of Ets-2. Biochemical assays demonstrated the ability of the p42 and p44 MAP kinases to phosphorylate Ets-2 on threonine 72. Importantly, in intact cells, the kinetics of phosphorylation of Ets-2 on this residue closely mirror the activation of the p42 and p44 MAP kinases and the observed onset of HB-EGF gene transcription following deltaRaf-1:ER activation. These data firmly establish Ets-2 as a direct target of the Raf-MEK-MAP kinase signaling pathway and strongly implicate Ets-2 in the regulation of HB-EGF gene expression.

Indexed as

DNA-Binding ProteinsTranscription Factors3T3 CellsAnimalsBase SequenceCalcium-Calmodulin-Dependent Protein KinasesDNA FootprintingEnzyme ActivationEpidermal Growth FactorGene Expression RegulationHeparinHeparin-binding EGF-like Growth FactorHumansIntercellular Signaling Peptides and ProteinsMiceMolecular Sequence DataCalcium-Calmodulin-Dependent Protein KinasesDNA-Binding ProteinsEpidermal Growth FactorERF protein, humanETS2 protein, humanEts2 protein, mouseHBEGF protein, humanHbegf protein, mouseHeparinHeparin-binding EGF-like Growth FactorIntercellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesProto-Oncogene Protein c-ets-2Proto-Oncogene ProteinsProto-Oncogene Proteins c-rafRepressor ProteinsTrans-ActivatorsTranscription Factor AP-1Transcription Factors

Identifiers

PMID9111309
PMCPMC232089
OpenAlexW2159335638

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.