Cited by 128Protein Kinase Regulation and GTPase SignalingCellular Mechanics and InteractionsGenomics and Chromatin Dynamics

Negative Regulation of the EGFR-MAPK Cascade by Actin-MAL-Mediated Mig6/Errfi-1 Induction

Open access
Descot, Arnaud, Hoffmann, Reinhard, Shaposhnikov, Dmitry, Reschke, Markus, Ullrich, Axel, Posern, Guido·2009·Molecular Cell

Abstract

We analyzed the G-actin-regulated transcriptome by gene expression analysis using previously characterized actin-binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF), as well as additional directly regulated genes. Surprisingly, several putative antiproliferative target genes were identified, including mig6/errfi-1, a negative regulator of the EGFR family. Mig6 induction occurred through actin-MAL-SRF signaling, and MAL was inducibly recruited to and activated a mig6 promoter element. Upregulation of Mig6 by lipid agonists such as LPA and S1P or actin drugs involved MAL and correlated with decreased activation of EGFR, MAPK/Erk, and c-fos. Mig6 depletion restored EGFR signaling and provided a proliferative advantage. Overexpression of MAL exhibited strong antiproliferative effects requiring the domains for SRF binding and transactivation, which supports antagonistic functions of MAL on growth-promoting signals. Our results show the existence of negatively acting transcriptional networks between pro- and antiproliferative signaling pathways toward SRF.

Integrity signals

Registry

Crossref · 10.1016/j.molcel.2009.07.015

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

1 of the 51 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Descot, A., Hoffmann, R., Shaposhnikov, D., Reschke, M., Ullrich, A., & Posern, G.
Affiliations
  • Max Planck Society (DE)
  • Technical University of Munich (DE)
Corresponding author
Posern, Guido
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2009-08
Volume
35
Issue
3
Pages
291-304
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2025275840
Cited by
128
References
51
Citations by year
2026: 3 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 24 · 2019: 3 · 2018: 10 · 2017: 7 · 2016: 6 · 2015: 12 · 2014: 9 · 2013: 12 · 2012: 7
FWCI
3.61
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion)
  • OPUS (Augsburg University) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (1032/2, PO 1032/1)
  • Ministry for Primary Industries
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
MIG6, serum response factor, EGFR signaling, MAPK/ERK pathway, c-fos, antiproliferative signaling, sphingosine-1-phosphate, LPA, transcriptional regulation, cell proliferation
MeSH terms
Actins, Animals, Cell Line, Cycloheximide, Gene Expression Regulation, Humans, Ligands, Myelin Proteins, Proteolipids, RNA, Messenger, Cytochalasin D, Bridged Bicyclo Compounds, Heterocyclic, Nucleic Acid Synthesis Inhibitors, Gene Expression Profiling, MAP Kinase Signaling System, Tumor Suppressor Proteins, Membrane Transport Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice, Thiazolidines, Myelin and Lymphocyte-Associated Proteolipid Proteins, ErbB Receptors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review