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Achieving high signal-to-noise in cell regulatory systems: Spatial organization of multiprotein transmembrane assemblies of FGFR and MET receptors.


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Authors

Blaszczyk, Michal 
Harmer, Nicholas J 
Chirgadze, Dimitri Y 
Ascher, David B 
Blundell, Tom L 

Abstract

How is information communicated both within and between cells of living systems with high signal to noise? We discuss transmembrane signaling models involving two receptor tyrosine kinases: the fibroblast growth factor receptor (FGFR) and the MET receptor. We suggest that simple dimerization models might occur opportunistically giving rise to noise but cooperative clustering of the receptor tyrosine kinases observed in these systems is likely to be important for signal transduction. We propose that this may be a more general prerequisite for high signal to noise in transmembrane receptor signaling.

Description

Keywords

Cell signaling, FGFR, MET receptor, Signal to noise, Transmembrane receptors, Cell Membrane, Protein Multimerization, Proto-Oncogene Proteins c-met, Receptors, Fibroblast Growth Factor, Signal Transduction

Journal Title

Prog Biophys Mol Biol

Conference Name

Journal ISSN

0079-6107
1873-1732

Volume Title

118

Publisher

Elsevier BV
Sponsorship
Bill & Melinda Gates Foundation (via Foundation for the National Institutes of Health (FNIH)) (ABELL11HTB0)
Wellcome Trust (093167/Z/10/Z)
D.B.A is the recipient of a C. J. Martin Research Fellowship from the National Health and Medical Research Council of Australia (APP1072476). TLB and MB receive funding from the Gates Foundation, and T.L.B. and D.Y.C. from The Wellcome Trust (093167) for facilities and support. D.Y.C. is also supported by the Crystallographic X-ray Facility, Department of Biochemistry, University of Cambridge. We thank Ermanno Gherardi for many contributions to the experiments and to our thinking on the Met receptor structure and activation over the years.