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Welcome!
Bih-Hwa Shieh, Ph.D.
Associate Professor of Pharmacology
Vanderbilt University Medical Center
402 Robinson Res Bldg (MRB1)
Nashville, TN 37232
Tel. (615) 343-0441
bih-hwa.shieh@vanderbilt.edu
Research
My laboratory is interested in understanding mechanisms of G-protein coupled phospholipase C-mediated signal transduction. We use Drosophila visual transduction as a model system for its feasibility in not only genetic and molecular biological analyses, but also biochemical and electrophysiological investigations.
Visual transduction is the process that converts the signal of light into a change of membrane potential in photoreceptors of the eye. In this signaling pathway, rhodopsin is activated by light and interacts with a heterotrimeric GTP-binding protein, Gq. Activated G-protein subsequently switches on a phospholipase C-beta (PLC-beta) that catalyzes the hydrolysis of phospholipid to generate two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular Ca2+ by interacting with IP3 receptors. DAG is a potent activator of protein kinase C (PKC). Downstream of PLC-beta, there are two channels, TRP (transient receptor potential) and TRPL (TRP-like), which are implicated in light-initiated depolarization of photoreceptors.
Our current efforts focus on a scaffolding protein named INAD. INAD contains five distinct PDZ domains and has been shown to interact with three key proteins in the visual cascade including PLC-beta, TRP and PKC leading to formation of a macromolecular complex. We are currently investigating how PKC modulates components of the complex by examining phosphorylation sites and analyzing the functional consequence of phosphorylation.
We are also extending our investigations to vertebrate INAD-like molecules. In particular, we are interested in MUPP1 (multiple PDZ protein 1) and its interaction with serotonin 5HT2c receptor. We have demonstrated that the MUPP1-receptor interaction can be regulated by agonist-induced phosphorylation of the receptor. Future directions include to identify additional MUPP1 interacting proteins as well as to investigate the consequence of the MUPP1-receptor interaction.