PRIMARY FACULTY

Ying-Hong Feng, Ph.D.
Associate Professor
Pharmacology
 
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-3232
Fax: 301-295-1996
yhfeng@usuhs.mil

Angiotensin II is an active hormane of the renin-angiotensin-aldosterone system that has been implicated in hypertension, heart failure, fibrosis, hypertrophy, stroke, diabetes, and cancer. It binds to type 1 and type 2 angiotensin II receptors (AT1 and AT2) of G protein-coupled receptor (GPCR) superfamily to exert diverse actions through network signal transductions. Thus, understanding the signaling network and structural mechanisms of AT1 and AT2 receptors becomes an important and exciting frontier of biomedical research.

For example, binding of Angiotensin II to AT1 receptor leads to transactivation of EGF (epidermal growth factor) receptor through undefined mechanisms. To identify the structural determinants of the AT1 receptor essential to the transactivation, a variety of AT1 mutant receptors are utilized to characterize the signal network and to map the critical residues. Our results indicate that the AT1 receptor is capable of transforming distinct multiple active states and also suggest that intracellular signaling molecules interacting directly with the AT1 receptor on the intracellular side play a pivotal role in determining which active state the receptor may transform. This mode of generation of multiple active states may represent a general paradigm for G protein-coupled receptors. Moreover, multiple active states of the AT1 receptor could serve as drug targets to block an undesired specific signaling pathway while leaving the other desired pathways unaffected.

Selected Publications

Resources