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

Randal A. Skidgel, PhD
Randal A. Skidgel, PhD

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.

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  1. McGwire, G. B., Tan, F., Michel, B., Rehli, M., and Skidgel, R. A. Identification of a membrane-bound carboxypeptidase as the mammalian homolog of duck gp180, a hepatitis B virus-binding protein. (1997) Life Sci. 60, 715-724.
  2. Tan, F., Rehli, M., Krause, S. W., and Skidgel, R. A. Sequence of human carboxypeptidase D reveals it to be a member of the regulatory carboxypeptidase family with three tandem active site domains. (1997) Biochem. J. 327, 81-87.
  3. Hadkar, V., and Skidgel, R. A. Carboxypeptidase D is up-regulated in RAW 264.7 macrophages and stimulates nitric oxide synthesis by cells in arginine-free medium. (2001) Mol. Pharmacol. 59, 1324-1332.
  4. Sangsree, S., Brovkovych, V., Minshall, R. D., and Skidgel, R. A. Kininase I-type carboxypeptidases enhance nitric oxide production in endothelial cells by generating bradykinin B1 receptor agonists. (2003) Am J Physiol Heart Circ Physiol 284, H1959-1968.
  5. Skidgel, R. A., and Erdös, E. G. Cellular carboxypeptidases. (1998) Immunol. Rev. 161, 129-141.