Evidence map›Paper›PMID 24095280›Full record

ArticleMolecular cell2013

Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 association and cell proliferation.

Che-Hung Shen, Ping Yuan, Rolando Perez-Lorenzo, Yaqing Zhang, Sze Xian Lee, Yang Ou, John M Asara, Lewis C Cantley, Bin Zheng

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
6.0field-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

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

  1. Pooled it
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  5. Translational control of AMPK activity in melanoma.Cell communication and signaling : CCS · 2026
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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Che-Hung ShenCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA; Department of Dermatology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Ping Yuan
Rolando Perez-Lorenzo
Yaqing Zhang
Sze Xian Lee
Yang Ou
John M Asara
Lewis C Cantley
Bin Zheng
Harvard University · USBeth Israel Deaconess Medical Center · USColumbia University Irving Medical Center · USCornell University · USUniversity of Michigan · US

Funding

Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
PROTEIN KINASE SIGNALING PATHWAYSR01GM056203 · NIGMS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CANTLEY, LEWIS C. · 1997 to 2012
$4.5M
Targeting the LKB1-AMPK PATHWAY in Melanoma: Mechanism and Preclinical EvaluationR01CA166717 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI ZHENG, BIN · 2012 to 2018
$1.7M
Regulation of LKB1 and AMPK Signaling by BRAF in MelanomaR00CA133245 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ZHENG, BIN · 2010 to 2012
$732k
NCI NIH HHS 2P01CA120964NCI NIH HHS 5P30CA00651648NCI NIH HHS P01-CA102694NCI NIH HHS P01 CA120964NCI NIH HHS R00 CA133245NCI NIH HHS R00-CA133245NCI NIH HHS R01 CA166717NCI NIH HHS R01-CA166717NIGMS NIH HHS R01 GM056203NIGMS NIH HHS R01 GM056302
6 · The paper itself

Abstract

BRAF is an oncogenic protein kinase that drives cell growth and proliferation through the MEK-ERK signaling pathway. BRAF inhibitors have demonstrated antitumor efficacy in melanoma therapy but have also been found to be associated with the development of cutaneous squamous cell carcinomas (cSCCs) in certain patients. Here, we report that BRAF is phosphorylated at Ser729 by AMP-activated protein kinase (AMPK), a critical energy sensor. This phosphorylation promotes the association of BRAF with 14-3-3 proteins and disrupts its interaction with the KSR1 scaffolding protein, leading to attenuation of the MEK-ERK signaling. We also show that phosphorylation of BRAF by AMPK impairs keratinocyte cell proliferation and cell-cycle progression. Furthermore, AMPK activation attenuates BRAF inhibitor-induced ERK hyperactivation in keratinocytes and epidermal hyperplasia in mouse skin. Our findings reveal a mechanism for regulating BRAF signaling in response to energy stress and suggest a strategy for preventing the development of cSCCs associated with BRAF-targeted therapy.

Indexed as

Cell ProliferationAMP-Activated Protein KinasesAnimalsCell CycleCell LineCell Line, TumorCells, CulturedChlorocebus aethiopsCOS CellsExtracellular Signal-Regulated MAP KinasesFemaleHEK293 CellsHumansImmunoblottingKeratinocytesMAP Kinase Signaling SystemAMP-Activated Protein KinasesExtracellular Signal-Regulated MAP KinasesKSR-1 protein kinaseProtein KinasesProto-Oncogene Proteins B-rafSerine

Identifiers

PMID24095280
PMCPMC3892895
OpenAlexW2038733728

What OpenQuestion holds

Textmetadata
LicenceTDM
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.