ArticleThe Biochemical journal2006
The epidermal growth factor receptor (EGFR)-S442F mutant displays increased affinity for neuregulin-2beta and agonist-independent coupling with downstream signalling events.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein.Pharmacological reviews · 2022Review
- Epiregulin: roles in normal physiology and cancer.Seminars in cell & developmental biology · 2014Review
- High-throughput de novo screening of receptor agonists with an automated single-cell analysis and isolation system.Scientific reports · 2014Article
- EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling.Growth factors (Chur, Switzerland) · 2012Review
- The Q43L mutant of neuregulin 2β is a pan-ErbB receptor antagonist.The Biochemical journal · 2012Article
- Ligand-based receptor tyrosine kinase partial agonists: New paradigm for cancer drug discovery?Expert opinion on drug discovery · 2011Article
- sZIP, an alternative splice variant of ZIP, antagonizes transcription repression and growth inhibition by ZIP.The Journal of biological chemistry · 2010Article
- Functional selectivity of EGF family peptide growth factors: implications for cancer.Pharmacology & therapeutics · 2009Review
- Altered EGFR localization and degradation in human breast cancer cells with an amphiregulin/EGFR autocrine loop.Cellular signalling · 2009Article
- Inter-conversion of neuregulin2 full and partial agonists for ErbB4.Biochemical and biophysical research communications · 2007Article
- Interactions among genes in the ErbB-Neuregulin signalling network are associated with increased susceptibility to schizophrenia.Behavioral and brain functions : BBF · 2007Article
- Mutational activation of ErbB family receptor tyrosine kinases: insights into mechanisms of signal transduction and tumorigenesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2007Review
- Rational optimization of a bispecific ligand trap targeting EGF receptor family ligands.Molecular medicine (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The EGFR (epidermal growth factor receptor; ErbB1) is frequently the subject of genetic changes in human tumours which contribute to the malignant phenotype by altering EGFR signalling. Examples of such genetic changes include overexpression, extracellular domain deletions and point mutations, and small deletions in the tyrosine kinase domain. We hypothesized that a point mutation in one of the EGFR ligand-binding domains would increase the affinity of EGFR for NRG2beta (neuregulin-2beta), which is not a potent stimulus of signalling by EGFR-Wt (wild-type EGFR). This mutation would permit NRG2beta stimulation of EGFR signalling in settings in which NRG2beta does not normally do so. To test this hypothesis, we have generated and evaluated various EGFR alleles containing mutations at Val441 and Ser442. NRG2beta is a much more potent stimulus of the EGFR-S442F mutant than of EGFR-Wt. Furthermore, the affinity of NRG2beta for the EGFR-S442F mutant is greater than the affinity of NRG2beta for EGFR-Wt. Finally, the EGFR-S442F mutant constitutively suppresses apoptosis via phosphoinositide 3-kinase and Akt signalling but is not highly tyrosine phosphorylated in the absence of ligand. These results suggest that mutations in the EGFR ligand-binding domain in tumours may permit potent stimulation of EGFR signalling by ligands that are not normally potent EGFR agonists, thereby providing for a novel mechanism by which EGFR signalling may be deregulated. These results also suggest that novel EGFR mutations and signalling activities may be responsible for deregulated EGFR signalling in tumour cells.
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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.