Evidence map›Paper›PMID 26124280›Full record

ArticleMolecular and cellular biology2015

Analysis of the Role of the C-Terminal Tail in the Regulation of the Epidermal Growth Factor Receptor.

Erika Kovacs, Rahul Das, Qi Wang, Timothy S Collier, Aaron Cantor, Yongjian Huang, Kathryn Wong, Amar Mirza, Tiago Barros, Patricia Grob and 3 more

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

Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

53 citing papers in PubMed, 89 citations in OpenAlex.

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  11. Computational analysis of regulatory regions in human protein kinases.Protein science : a publication of the Protein Society · 2023
    Article
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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

13 authors at 5 institutions in 1 country.

Erika KovacsDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Rahul DasDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Qi WangDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Timothy S CollierDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Aaron CantorDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Yongjian HuangDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Kathryn WongDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Amar MirzaHoward Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Tiago BarrosDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Patricia GrobDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
Natalia JuraCardiovascular Research Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.
Ron BoseDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
John KuriyanDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA Department of Chemistry, University of California, Berkeley, Berkeley, California, USA Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA kuriyan@berkeley.edu.
University of California, Berkeley · USQB3 · USHoward Hughes Medical Institute · USWashington University in St. Louis · USUniversity of California, San Francisco · US

Funding

YOGA LIFESTYLE INTERVENTION REDUCES BLOOD PRESSURE IN HIV-INFECTED ADULTSP41RR000954 · NCRR · WASHINGTON UNIVERSITY · PI GROSS, MICHAEL L · 1985 to 2011
$16.0M
PRE-AND POSTGRADUATE TRAINING IN MOLECULAR HEMATOLOGYT32HL007088 · NHLBI · WASHINGTON UNIVERSITY · PI Grant Anthony Challen, Stephen Oh · 1985 to 2026
$14.1M
Engineered Antibody EGFR Antagonist Cancer TherapeuticsR01CA096504 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WITTRUP, KARL DANE · 2002 to 2017
$9.7M
Univ of Calif Berkeley Chemistry-Biology Interface ProgramT32GM066698 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHANG, CHRISTOPHER J., FRANCIS, MATTHEW B · 2004 to 2023
$7.5M
MECHANISMS OF HER2 HETERODIMERIZATIONR01CA161001 · NCI · WASHINGTON UNIVERSITY · PI BOSE, RON · 2013 to 2017
$1.6M
NCI NIH HHS 2R01CA09650406NCI NIH HHS R01 CA096504NCI NIH HHS R01 CA161001NCI NIH HHS R01CA161001NCRR NIH HHS 2P41RR000954NCRR NIH HHS P41 RR000954NHLBI NIH HHS 2T32HL007088-36NHLBI NIH HHS T32 HL007088NIGMS NIH HHS T32 GM066698
6 · The paper itself

Abstract

The ∼230-residue C-terminal tail of the epidermal growth factor receptor (EGFR) is phosphorylated upon activation. We examined whether this phosphorylation is affected by deletions within the tail and whether the two tails in the asymmetric active EGFR dimer are phosphorylated differently. We monitored autophosphorylation in cells using flow cytometry and found that the first ∼80 residues of the tail are inhibitory, as demonstrated previously. The entire ∼80-residue span is important for autoinhibition and needs to be released from both kinases that form the dimer. These results are interpreted in terms of crystal structures of the inactive kinase domain, including two new ones presented here. Deletions in the remaining portion of the tail do not affect autophosphorylation, except for a six-residue segment spanning Tyr 1086 that is critical for activation loop phosphorylation. Phosphorylation of the two tails in the dimer is asymmetric, with the activator tail being phosphorylated somewhat more strongly. Unexpectedly, we found that reconstitution of the transmembrane and cytoplasmic domains of EGFR in vesicles leads to a peculiar phenomenon in which kinase domains appear to be trapped between stacks of lipid bilayers. This artifactual trapping of kinases between membranes enhances an intrinsic functional asymmetry in the two tails in a dimer.

Indexed as

Amino Acid SequenceAnimalsCell LineChlorocebus aethiopsCOS CellsCrystallography, X-RayEnzyme ActivationErbB ReceptorsFlow CytometryHEK293 CellsHumansMolecular Dynamics SimulationPhosphorylationProtein Structure, TertiarySequence DeletionErbB Receptors

Identifiers

PMID26124280
PMCPMC4525312
OpenAlexW2166567143

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.