ArticleScientific reports2016
Feedback control of ErbB2 via ERK-mediated phosphorylation of a conserved threonine in the juxtamembrane domain.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Erk inhibitors intercept Erk-mediated negative feedback while imposing cell-cycle arrest and activating p38.iScience · 2026Article
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- Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells.Cell reports · 2024Article
- Oncogenic ERRB2 signals through the AP-1 transcription factor to control mesenchymal-like properties of oesophageal adenocarcinoma.NAR cancer · 2023Article
- The Hub Genes Related to Osteoporosis Were Identified by Bioinformatics Analysis.BioMed research international · 2023Article
- TcdB ofInternational journal of molecular sciences · 2022Article
- The RXR Agonist MSU42011 Is Effective for the Treatment of Preclinical HER2+ Breast Cancer and Kras-Driven Lung Cancer.Cancers · 2021Article
- Cell Type-specific Adaptive Signaling Responses to KRASClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Dabrafenib Promotes Schwann Cell Differentiation by Inhibition of the MEK-ERK Pathway.Molecules (Basel, Switzerland) · 2021Article
- The MEK/ERK Network as a Therapeutic Target in Human Cancer.Molecular cancer research : MCR · 2021Review
- Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor ThrScientific reports · 2020Article
- ERK-mediated negative feedback regulation of oncogenic EGFRvIII in glioblastoma cells.Oncology letters · 2020Article
- The Effects of Pertuzumab and Its Combination with Trastuzumab on HER2 Homodimerization and Phosphorylation.Cancers · 2019Article
- ErbB3 Targeting Enhances the Effects of MEK Inhibitor in Wild-Type BRAF/NRAS Melanoma.Cancer research · 2018Article
- Mechanisms for DNA-damaging agent-induced inactivation of ErbB2 and ErbB3 via the ERK and p38 signaling pathways.Oncology letters · 2018Article
- Combined targeting of Raf and Mek synergistically inhibits tumorigenesis in triple negative breast cancer model systems.Oncotarget · 2017Article
- EGFR Family Members' Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer.Cancers · 2017Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase activity of the asymmetric EGFR homodimer is negatively regulated via ERK-mediated phosphorylation of Thr-669 in the juxtamembrane domain. In the present study, we investigated in human breast cancer cells whether a similar mechanism plays a role in the feedback regulation of the ErbB2/ErbB3 heterodimer, the most potent ErbB receptor dimer. Constitutive tyrosine phosphorylation of ErbB2 and ErbB3 was significantly decreased in phorbol ester- and growth factor-treated BT-474 and MDA-MB-453 cells. In contrast to the decreased tyrosine phosphorylation, Phos-tag Western blot analysis revealed that TPA induced phosphorylation of ErbB2 in an ERK-dependent manner. The target threonine residue corresponding to EGFR Thr-669 and the surrounding residues are highly conserved in ErbB2, but not in ErbB3. Therefore, we demonstrated ERK-mediated phosphorylation of ErbB2 at Thr-677 by generating phospho-specific monoclonal antibodies. Moreover, treatment with trametinib and SCH772984, inhibitors of the MEK-ERK pathway, and substitution of Thr-677 to alanine impaired the feedback inhibition of ErbB2 and ErbB3. These results demonstrated that ERK-mediated phosphorylation of the conserved threonine is a common mechanism for the negative feedback control of active ErbB receptor dimers.
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