Findings from Swinburne University of Technology in Receptor Protein-Tyrosine Kinases Reported (Exploring higher-order EGFR oligomerisation and phosphorylation--a combined experimental and theoretical approach)
By a News Reporter-Staff News Editor at Life Science Weekly -- Investigators publish new report on Membrane Proteins. According to news reporting originating in Hawthorn, Australia, by NewsRx journalists, research stated, "The epidermal growth factor receptor (EGFR) kinase is generally considered to be activated by either ligand-induced dimerisation or a ligand-induced conformational change within pre-formed dimers. Ligand-induced higher-order EGFR oligomerisation or clustering has been reported but it is not clear how EGFR oligomers, as distinct from EGFR dimers, influence signaling outputs."
The news reporters obtained a quote from the research from the Swinburne University of Technology, "To address this question, we combined measures of receptor clustering (microscopy; image correlation spectroscopy) and phosphorylation (Western blots) with modelling of mass-action chemical kinetics. A stable BaF/3 cell-line that contains a high proportion (>90%) of inactive dimers of EGFR-eGFP but no secreted ligand and no other detectable ErbB receptors was used as the model cell system. EGF at concentrations of greater than 1 nM was found to cluster EGFR-eGFP dimers into higher-order complexes and cause parallel increases in EGFR phosphorylation. The kinetics of EGFR clustering and phosphorylation were both rapid, plateauing within 2 minutes after stimulation with 30 nM EGF. A rule-based model was formulated to interpret the data. This model took into account ligand binding, ligand-induced conformational changes in the cytosolic tail, monomer-dimer-trimer-tetramer transitions via ectodomain-and kinase-mediated interactions, and phosphorylation."
According to the news reporters, the research concluded: "The model predicts that cyclic EGFR tetramers are the predominant phosphorylated species, in which activated receptor dimers adopt a cyclic side-by-side orientation, and that receptor kinase activation is stabilised by the intramolecular interactions responsible for cyclic tetramerization."
For more information on this research see: Exploring higher-order EGFR oligomerisation and phosphorylation--a combined experimental and theoretical approach. Molecular Biosystems, 2013;9(7):1849-63. (Royal Society of Chemistry - www.rsc.org/; Molecular Biosystems - pubs.rsc.org/en/journals/journalissues/mb)
Our news correspondents report that additional information may be obtained by contacting N. Kozer, Centre for Micro-Photonics, Faculty of Engineering and Industrial Sciences, Cell Biophysics Laboratory, Swinburne University of Technology, PO Box 218, Hawthorn, Victoria 3122, Australia. Additional authors for this research include D. Barua, S. Orchard, E.C. Nice, A.W. Burgess, W.S. Hlavacek and A.H Clayton (see also Membrane Proteins).
Keywords for this news article include: Hawthorn, Protein Kinases, Membrane Proteins, Phosphotransferases, Enzymes and Coenzymes, Australia and New Zealand, Epidermal Growth Factor Receptor, Receptor Protein Tyrosine Kinases, Gastrointestinal Hormone Receptors, Intercellular Signaling Peptides and Proteins.
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