Structure-function studies of ligand-induced epidermal growth factor receptor dimerization

Biochemistry
B NeelamD E Davies

Abstract

We present a novel 96-well assay which we have applied to a structure-function study of epidermal growth factor receptor dimerization. The basis of the assay lies in the increased probability of EGFRs being captured as dimers by a bivalent antibody when they are immobilized in the presence of a cognate ligand. Once immobilized, the antibody acts as a tether, retaining the receptor in its dimeric state with a resultant 5-7-fold increase in binding of a radiolabeled ligand probe. When the assay was applied to members of the EGF ligand family, murine EGF, transforming growth factor alpha, and heparin-binding EGF-like growth factor were comparable with human EGF (EC50 = 2nM); betacellulin, which has a broader receptor specificity, was slightly less effective. In contrast, amphiregulin (AR1-84), which has a truncated C-tail and lacks a conserved leucine residue, was ineffective unless used at >1 microM. We further probed the involvement of the C-tail and the conserved leucine residue in receptor dimerization by comparing the activities of two genetically modified EGFs (the chimera mEGF/TGFalpha44-50 and the EGF point mutant L47A) and a C-terminally extended form of AR (AR1-90) with those of two other unrelated EGF mutants (I23T and ...Continue Reading

References

Jul 1, 1991·Journal of Cellular Biochemistry·R K MatsunamiS K Niyogi
Apr 20, 1990·Cell·A Ullrich, J Schlessinger
Jan 1, 1982·Journal of Cellular Biochemistry·M D WaterfieldB Ozanne
Jan 1, 1994·Progress in Nucleic Acid Research and Molecular Biology·S R Campion, S K Niyogi
Jan 15, 1997·The EMBO Journal·M A LemmonJ Schlessinger

❮ Previous
Next ❯

Citations

Jan 10, 2004·The Journal of Allergy and Clinical Immunology·Riccardo PolosaDonna E Davies
Mar 22, 2003·Experimental Cell Research·Robert N JorissenAntony W Burgess
Dec 6, 2001·European Journal of Biochemistry·S G ChamberlinD L Turner
Jan 28, 2014·Seminars in Cell & Developmental Biology·Carmen Berasain, Matías A Avila
Jan 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Naoe TairaKiyotsugu Yoshida
Feb 12, 2005·BJU International·Richard T BryanD Michael A Wallace
Sep 24, 2011·Journal of Oncology·Takuji TanakaKoji Suzuki
Jan 18, 2008·Biophysical Journal·Ibon IloroBelinda Pastrana-Ríos
Aug 12, 2005·Journal of Biomolecular Screening·Frank H BüttnerMartin J Valler
Nov 30, 2007·The Biochemical Journal·Kathryn A SternNancy L Lill
Jun 9, 2017·Archivum Immunologiae Et Therapiae Experimentalis·Margherita SistoSabrina Lisi
Feb 28, 2004·The Journal of Biological Chemistry·Susana M Casalino-MatsudaRosanna M Forteza
Mar 28, 2021·Nature Communications·Junichi SugitaIssei Komuro
Oct 27, 2021·Journal of Cellular Physiology·Siddharth S SinghRajiv Kumar

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.