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Peter Friedman
Biomedical Masters Program
Email: paf10@pitt.edu
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Ligand bias, signaling, and trafficking of the parathyroid hormone receptor
Date Added: 7/31/2003 12:00:00 AM
Last Updated: 11/5/2008 12:00:00 AM
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Description of projects available to graduate students:
Studies in our lab focus on regulation of parathyroid hormone (PTH) receptor signaling and regulated trafficking. PTH regulates bone remodeling and calcium homeostasis Current attention centers on the role of cytoplasmic adapter proteins that modify and control all aspects of PTH receptor signaling and trafficking. PTH controls extracellular calcium and inorganic phosphate homeostasis. Its effects on kidney and bone are mediated by its cognate receptor, the type I PTH receptor (PTH1R). Key advances have been made in cell-specific PTH1R signaling and trafficking. Recent observations indicate that PTH1R activation and desensitization/endocytosis are mediated through distinct structural states that derive from specific interactions between ligand and receptor. Agonist- or antagonist-occupied receptor states induce discrete conformations with accessibility to intracellular receptor domains. The differential or inducible involvement of these domains in coupling to G proteins may represent a molecular basis for ligand-selective responses not only for the PTH1R, but also for other GPCRs. Work in progress is directed at elucidating the molecular and structural mechanisms of how these cytoplasmic scaffold proteins legislate cell-specific receptor internalization and ubiquitination.
Techniques graduate student will learn:
Trainees are introduced to the basic concepts of G protein-coupled biology and use state-of-the-art analytic fluorescence techniques and biochemical and simple molecular biological assays to analyze receptor recycling and signaling through adenylyl cyclase or phospholipase C pathways using convenient cell culture models.
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