The GPCR-interactome: a comprehensive membrane protein interaction map of the human G-Protein Coupled Receptors (GPCRs).
Lukas Bürkle (1), Michael Fetchko (1), Daniel Auerbach (2), Igor Stagljar (1)
(1) Vet. Biochem and Mol Biology, Universtiy of Zürich-Irchel, Winterthurerstr. 190, Zurich, CH-8057, Switzerland;
(2) Dualsystems Biotech Inc., Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
As biology enters the so-called 'Post-Genomics' era, researchers have begun to embrace the exciting opportunity of investigating proteins in high-throughput experiments. GPCRs constitute one of the most important families of membrane receptors through which cells communicate with each other and organisms adapt to changes in the internal and external milieus. Their medical importance is reflected by the fact that they are targeted by 60% of all medicines making them extremely valuable targets for the pharmaceutical industry. In humans, this family of receptors has been proposed to contain approximately 1'500 members. However, only approximately 700 human GPCRs have been identified so far and their communication with other cellular components is only poorly understood. Previously, we have developed a genetic method for the in vivo detection of membrane protein interactions in S. cerevisiae, so-called membrane-based yeast two-hybrid (MbYTH) system (Stagljar et al. (1998)), and have recently adapted it for prey library screening (Thaminy et al. (2003) Genome Res). Our current effort is directed at generating a comprehensive protein interaction network of the human GPCRs. Such a proteomic approach should reveal many unknown regulatory pathways and will provide the framework upon which a systems biology understanding of GPCR function will be developed. We will present the latest achievements on this project and the results of our preliminary screenings.
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