ArticleThe Journal of biological chemistry2012
Flotillin-1/reggie-2 protein plays dual role in activation of receptor-tyrosine kinase/mitogen-activated protein kinase signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 128 citations in OpenAlex.
- Loss of Flotillin-2 enhances trastuzumab emtansine internalization and cytotoxicity by relieving negative regulation of HER2 internalization in HER2-amplified cancers.bioRxiv : the preprint server for biology · 2026Article
- Role of Flotillin-1 In Listeria monocytogenes Cell-to-Cell Spreading.The Journal of infectious diseases · 2025Article
- The role of SUMOylation in epithelial-mesenchymal transition.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Identification of miR-71* as a regulator of Flotillin-1 in egg development of Rhipicephalus sanguineus.Veterinary research communications · 2025Article
- Comprehensive Review on Bimolecular Fluorescence Complementation and Its Application in Deciphering Protein-Protein Interactions in Cell Signaling Pathways.Biomolecules · 2024Review
- Flotillin-1 palmitoylation is essential for its stability and subsequent tumor promoting capabilities.Oncogene · 2024Article
- LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL.Cell death & disease · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Unraveling the prevalence of various signalling pathways in non-small-cell lung cancer: a review.Molecular and cellular biochemistry · 2023Review
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Confinement of unliganded EGFR by tetraspanin nanodomains gates EGFR ligand binding and signaling.Nature communications · 2023Article
- FLOT1 knockdown inhibits growth of AML cells through triggering apoptosis and pyroptosis.Annals of hematology · 2023Article
- Flotillin-1 is a prognostic biomarker for glioblastoma and promotes cancer development through enhancing invasion and altering tumour microenvironment.Journal of cellular and molecular medicine · 2023Article
- Article
- FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling.International journal of biological sciences · 2023Article
- SDC1-TGM2-FLOT1-BHMT complex determines radiosensitivity of glioblastoma by influencing the fusion of autophagosomes with lysosomes.Theranostics · 2023Article
- The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer.eLife · 2022Article
- The differential role of the lipid raft-associated protein flotillin 2 for progression of myeloid leukemia.Blood advances · 2022Article
- MPP1 Determines the Mobility of Flotillins and Controls the Confinement of Raft-Associated Molecules.Cells · 2022Article
- Identification of a new regulation pathway of EGFR and E-cadherin dynamics.Scientific reports · 2021Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous work has shown that the membrane microdomain-associated flotillin proteins are potentially involved in epidermal growth factor (EGF) receptor signaling. Here we show that knockdown of flotillin-1/reggie-2 results in reduced EGF-induced phosphorylation of specific tyrosines in the EGF receptor (EGFR) and in inefficient activation of the downstream mitogen-activated protein (MAP) kinase and Akt signaling. Although flotillin-1 has been implicated in endocytosis, its depletion affects neither the endocytosis nor the ubiquitination of the EGFR. However, EGF-induced clustering of EGFR at the cell surface is altered in cells lacking flotillin-1. Furthermore, we show that flotillins form molecular complexes with EGFR in an EGF/EGFR kinase-independent manner. However, knockdown of flotillin-1 appears to affect the activation of the downstream MAP kinase signaling more directly. We here show that flotillin-1 forms a complex with CRAF, MEK1, ERK, and KSR1 (kinase suppressor of RAS) and that flotillin-1 knockdown leads to a direct inactivation of ERK1/2. Thus, flotillin-1 plays a direct role during both the early phase (activation of the receptor) and late (activation of MAP kinases) phase of growth factor signaling. Our results here unveil a novel role for flotillin-1 as a scaffolding factor in the regulation of classical MAP kinase signaling. Furthermore, our results imply that other receptor-tyrosine kinases may also rely on flotillin-1 upon activation, thus suggesting a general role for flotillin-1 as a novel factor in receptor-tyrosine kinase/MAP kinase signaling.
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Registered trials
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.