Randal A. Skidgel, PhD, University of Illinois at Chicago

The Skidgel lab seeks 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. Their 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). They 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. They 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, Gai, Src kinase and MAP kinases Erk1/2 and p38. They are also investigating the functional consequences of B1 receptor activation and super-high output NO production in the regulation of endothelial barrier function.

Part of The Investigator's Annexe program.