Evidence map›Paper›PMID 29514089›Full record

ArticleCell reports2018

Phosphorylated EGFR Dimers Are Not Sufficient to Activate Ras.

Samantha I Liang, Bettina van Lengerich, Kelsie Eichel, Minkwon Cha, David M Patterson, Tae-Young Yoon, Mark von Zastrow, Natalia Jura, Zev J Gartner

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

47 citing papers in PubMed, 79 citations in OpenAlex.

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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 4 institutions in 2 countries.

Samantha I LiangDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Program in Biochemistry and Molecular Biology, University of California, San Francisco, San Francisco, CA, USA.
Bettina van LengerichCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Kelsie EichelProgram in Biochemistry and Molecular Biology, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
Minkwon ChaDepartment of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea; Center for Nanomedicine, Institute for Basic Science (IBS), Yonsei University, Seoul 30722, South Korea; Yonsei-IBS Institute, Yonsei University, Seoul 30722, South Korea.
David M PattersonDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Tae-Young YoonCenter for Nanomedicine, Institute for Basic Science (IBS), Yonsei University, Seoul 30722, South Korea; Yonsei-IBS Institute, Yonsei University, Seoul 30722, South Korea; Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea.
Mark von ZastrowDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
Natalia JuraCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: natalia.jura@ucsf.edu.
Zev J GartnerDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA, USA; Center for Cellular Construction, University of California, San Francisco, San Francisco, CA, USA. Electronic address: zev.gartner@ucsf.edu.
University of California, San Francisco · USInstitute for Basic Science · KRUniversity of San Francisco · USYonsei University · KR

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Rewiring Therapeutic Cells: User-Controlled T Cells and Stem CellsP50GM081879 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2010 to 2017
$19.0M
The Presynaptic Vesicle Cycle for the Slow Acting Neurotransmitter SecretionP01DA010154 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARDS, ROBERT H, KREITZER, ANATOL · 1995 to 2016
$14.7M
Total synthesis of the human mammary glandDP2HD080351 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GARTNER, ZEV JORDAN · 2013 to 2013
$2.4M
Structural and Functional Studies of HER Receptor Tyrosine KinasesR01GM109176 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JURA, NATALIA · 2014 to 2018
$1.8M
NCRR NIH HHS UL1 RR024131NICHD NIH HHS DP2 HD080351NIDA NIH HHS P01 DA010154NIGMS NIH HHS P50 GM081879NIGMS NIH HHS R01 GM109176
6 · The paper itself

Abstract

Growth factor binding to EGFR drives conformational changes that promote homodimerization and transphosphorylation, followed by adaptor recruitment, oligomerization, and signaling through Ras. Whether specific receptor conformations and oligomerization states are necessary for efficient activation of Ras is unclear. We therefore evaluated the sufficiency of a phosphorylated EGFR dimer to activate Ras without growth factor by developing a chemical-genetic strategy to crosslink and "trap" full-length EGFR homodimers on cells. Trapped dimers become phosphorylated and recruit adaptor proteins at stoichiometry equivalent to that of EGF-stimulated receptors. Surprisingly, these phosphorylated dimers do not activate Ras, Erk, or Akt. In the absence of EGF, phosphorylated dimers do not further oligomerize or reorganize on cell membranes. These results suggest that a phosphorylated EGFR dimer loaded with core signaling adapters is not sufficient to activate Ras and that EGFR ligands contribute to conformational changes or receptor dynamics necessary for oligomerization and efficient signal propagation through the SOS-Ras-MAPK pathway.

Indexed as

Protein MultimerizationClathrin-Coated VesiclesCross-Linking ReagentsEpidermal Growth FactorErbB ReceptorsHEK293 CellsHumansLigandsPhosphorylationPhosphotyrosineProtein Conformationras ProteinsSignal TransductionCross-Linking ReagentsEpidermal Growth FactorErbB ReceptorsLigandsPhosphotyrosineras Proteinschemical-genetic dimerizationEGFR nanoclustersEGFR signalingRas-MAPK signalingspatial reorganization

Identifiers

PMID29514089
PMCPMC5916813
OpenAlexW2791529256

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.