ArticleMolecular biology of the cell2005
The membrane-anchoring domain of epidermal growth factor receptor ligands dictates their ability to operate in juxtacrine mode.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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.
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.
Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Altered bone marrow niche forms central innate immune memory driving cardiac dysfunction.Nature communications · 2026Article
- ERBB Receptors and Their Ligands in the Developing Mammary Glands of Different Species: Fifteen Characters in Search of an Author.Journal of mammary gland biology and neoplasia · 2023Review
- Metastasis and MAPK Pathways.International journal of molecular sciences · 2022Review
- Article
- Co-culture Activation of MAP Kinase in Drosophila S2 Cells.Methods in molecular biology (Clifton, N.J.) · 2017Article
- GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast.Hormones & cancer · 2014Article
- Trafficking of the EGFR ligand Spitz regulates its signaling activity in polarized tissues.Journal of cell science · 2013Article
- Epidermal growth factor cytoplasmic domain affects ErbB protein degradation by the lysosomal and ubiquitin-proteasome pathway in human cancer cells.Neoplasia (New York, N.Y.) · 2012Article
- Transautocrine signaling by membrane neuregulins requires cell surface targeting, which is controlled by multiple domains.The Journal of biological chemistry · 2011Article
- Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression.BMC cancer · 2011Article
- EGFR signaling in breast cancer: bad to the bone.Seminars in cell & developmental biology · 2010Review
- The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release.Journal of cell science · 2010Article
- Sequential and gamma-secretase-dependent processing of the betacellulin precursor generates a palmitoylated intracellular-domain fragment that inhibits cell growth.Journal of cell science · 2010Article
- Multiple mechanisms are responsible for transactivation of the epidermal growth factor receptor in mammary epithelial cells.The Journal of biological chemistry · 2008Article
- The cytoplasmic domain of proEGF negatively regulates motility and elastinolytic activity in thyroid carcinoma cells.Neoplasia (New York, N.Y.) · 2008Article
- The extracellular linker of pro-neuregulin-alpha2c is required for efficient sorting and juxtacrine function.Molecular biology of the cell · 2007Article
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 3 institutions in 1 country.
Funding
Abstract
All ligands of the epidermal growth factor (EGF) receptor (EGFR) are synthesized as membrane-anchored precursors. Previous work has suggested that some ligands, such as EGF, must be proteolytically released to be active, whereas others, such as heparin-binding EGF-like growth factor (HB-EGF) can function while still anchored to the membrane (i.e., juxtacrine signaling). To explore the structural basis for these differences in ligand activity, we engineered a series of membrane-anchored ligands in which the core, receptor-binding domain of EGF was combined with different domains of both EGF and HB-EGF. We found that ligands having the N-terminal extension of EGF could not bind to the EGFR, even when released from the membrane. Ligands lacking an N-terminal extension, but possessing the membrane-anchoring domain of EGF, still required proteolytic release for activity, whereas ligands with the membrane-anchoring domain of HB-EGF could elicit full biological activity while still membrane anchored. Ligands containing the HB-EGF membrane anchor, but lacking an N-terminal extension, activated EGFR during their transit through the Golgi apparatus. However, cell-mixing experiments and fluorescence resonance energy transfer studies showed that juxtacrine signaling typically occurred in trans at the cell surface, at points of cell-cell contact. Our data suggest that the membrane-anchoring domain of ligands selectively controls their ability to participate in juxtacrine signaling and thus, only a subclass of EGFR ligands can act in a juxtacrine mode.
Indexed as
Identifiers
What OpenQuestion holds
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.