ArticleThe Journal of biological chemistry2009
GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia.Carcinogenesis · 2015Pooled it
- Structural and Biochemical Analysis of the CABIT1 Domain of THEMIS.bioRxiv : the preprint server for biology · 2026Article
- Structural and mechanistic insights into the constitutive Themis-Grb2 complex in T cell signalling.Nature communications · 2026Article
- Increased KCNQ3 expression in papillary thyroid cancer promotes proliferation and migration.Cancer cell international · 2025Article
- Oncogenic KRAS Mutations Confer a Unique Mechanotransduction Response to Peristalsis in Colorectal Cancer Cells.Molecular cancer research : MCR · 2025Article
- The Configuration of GRB2 in Protein Interaction and Signal Transduction.Biomolecules · 2024Review
- Sticky, Adaptable, and Many-sided: SAM protein versatility in normal and pathological hematopoietic states.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Integrated analysis of lncRNAs and mRNAs by RNA-Seq in secondary hair follicle development and cycling (anagen, catagen and telogen) of Jiangnan cashmere goat (Capra hircus).BMC veterinary research · 2022Article
- Negative times negative equals positive, THEMIS sets the rule on thymic selection and peripheral T cell responses.Biomedical journal · 2022Review
- Synergy and allostery in ligand binding by HIV-1 Nef.The Biochemical journal · 2021Article
- Effect of the glycine-rich domain in GAREM2 on its unique subcellular localization upon EGF stimulation.Cellular & molecular biology letters · 2021Article
- Investigation of the Genome-Wide Genetic and Epigenetic Networks for Drug Discovery Based on Systems Biology Approaches in Colorectal Cancer.Frontiers in genetics · 2020Article
- Behavioral analysis in mice deficient for GAREM2 (Grb2-associated regulator of Erk/MAPK subtype2) that is a subtype of highly expressing in the brain.Molecular brain · 2019Article
- A Decade of GWAS Results in Lung Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018Review
- GAREM1 regulates the PR interval on electrocardiograms.Journal of human genetics · 2018Article
- THEMIS: Two Models, Different Thresholds.Trends in immunology · 2017Review
- Deep Coverage of Global Protein Expression and Phosphorylation in Breast Tumor Cell Lines Using TMT 10-plex Isobaric Labeling.Journal of proteome research · 2017Article
- Early signaling dynamics of the epidermal growth factor receptor.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Themis2 is not required for B cell development, activation, and antibody responses.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Development of a 5-plex SILAC method tuned for the quantitation of tyrosine phosphorylation dynamics.Molecular & cellular proteomics : MCP · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptor proteins for the various growth factor receptors play a crucial role in signal transduction through tyrosine phosphorylation. Several candidates for adaptor proteins with potential effects on the epidermal growth factor (EGF) receptor-mediated signaling pathway have been identified by recent phosphoproteomic studies. Here, we focus on a novel protein, GAREM (Grb2-associated and regulator of Erk/MAPK) as a downstream molecule of the EGF receptor. GAREM is phosphorylated at tyrosine 105 and 453 after EGF stimulation. Grb2 was identified as its binding partner, and the proline-rich motifs of GAREM are recognized by the N- and C-terminal SH3 domains of Grb2. In addition, the tyrosine phosphorylations of GAREM are necessary for its binding to Grb2. Because the amino acid sequence surrounding tyrosine 453 is similar to the immunoreceptor tyrosine-based inhibitory motif, Shp2, a positive regulator of Erk, binds to GAREM in this phosphorylation-dependent manner. Consequently, Erk activation in response to EGF stimulation is regulated by the expression of GAREM in COS-7 and HeLa cells, which occurs independent of the presence of other binding proteins, such as Gab1 and SOS, to the activated EGF receptor. Furthermore, the expression of GAREM has an effect on the transformation activity of cultured cells. Together, these findings suggest that GAREM plays a key role in the ligand-mediated signaling pathway of the EGF receptor and the tumorigenesis of cells.
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