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Randal A. Skidgel, PhD

Professor of Pharmacology and Anesthesiology
Director of Graduate Studies
Center for Lung and Vascular Biology

skidgel
We are seeking to understand the important roles of membrane carboxypeptidase M in the regulation of peptide hormone activity and receptor signaling leading to high output nitric oxide production in the cardiovascular system. Our studies revealed that carboxypeptidase M on the surface of cytokine-stimulated endothelial cells efficiently converts bradykinin (a B2 receptor agonist) into des-Arg9-bradykinin, a B1 agonist, generating a significant and prolonged output of nitric oxide (NO). We are investigating the structure and function of CPM on the plasma membrane and its ability to form a receptor-enzyme signaling complex with the B1 receptor, a GPCR. We are also studying novel signaling pathways by which the activation of the kinin B1 receptor generates a hyperactive iNOS resulting from activation of the heterotrimeric G protein, Gαi, Src kinase and MAP kinases Erk1/2 and p38. We are also investigating the functional consequences of B1 receptor activation and super-high output NO production in the regulation of endothelial barrier function.

406 CMW
1853 W. Polk St.
(312) 996-9179
rskidgel@uic.edu

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