|Department Affiliations||Medicine, Biological Chemistry, Pulmonary and Critical Care Medicine|
|Rank||Professor and Executive Vice Dean|
|SOM Address||100 Miller Research Building|
Aquaporins are water-specific membrane channel proteins. Multiple mammalian homologues have been identified, each with a distinct tissue distribution. Four aquaporins have been identified in the respiratory tract, and functional studies indicate that that they participate in regulation of both endothelial and epithelial water permeability in the lung. Aquaporins appear to be dynamically regulated at multiple levels, from transcriptional activation of the genes through changes in stability of the protein to trafficking on and off of the membrane. We are currently dissecting the molecular mechanisms regulating each of these steps for respiratory tract aquaporins. We hope to understand how these proteins contribute to water homeostasis in the respiratory tract, and how their expression or function may be altered in disease states.
- Hoffert, J., V. Leitch, P. Agre, King, L.S., 2000. Hypertonic induction of AQP5 expression through an ERK dependent pathway. J. Biol. Chem. 275:9070-9077
- Tsubota, K., Hirai, S., King, L.S., Agre, P., Ishida, N. 2001 Defective cellular trafficking of aquaporin-5 water channel protein in Sj?n’s syndrome lacrimal glands. Lancet, 357:688-689
- Leitch, V., Agre, P., King, L.S., 2001. Altered ubiquitination and stability of aquaporin-1 in hypertonic stress. Proc. Natl. Acad. Sci. USA, 98:2894-2898.
- King, L.S., Choi, M., Cartron, J-P, Agre, P. 2001. Defective urinary concentrating ability due to a complete deficiency of aquaporin-1. N. Engl. J. Med. 345:175-179.
- King, L.S., Nielsen, S., Agre, P., Brown, R. 2002. Decreased pulmonary vascular permeability in aquaporin-1 null humans. Proc. Natl. Acad. Sci. 99:1059-1063
- Kozono, D., Yasui, M., King, L.S., Agre, P. 2002. Aquaporin water channels: atomic structure and molecular dynamics meet clinical medicine. J. Clin. Invest. 109:1395-1399.
- Herrlich A, Leitch V, King LS. 2004. Role of proneuregulin 1 cleavage and human epidermal growth factor receptor activation in hypertonic aquaporin induction. Proc Natl Acad Sci U S A. 101(44):15799-15804.
- Gresz V, Kwon TH, Gong H, Agre P, Steward MC, King LS, Nielsen S. 2004. Immunolocalization of AQP-5 in rat parotid and submandibular salivary glands after stimulation or inhibition of secretion in vivo. Am J Physiol Gastrointest Liver Physiol. 287(1):G151-G161.
- King LS, Kozono D, Agre P. From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol. 25(9): 687-698. Review, 2004.
- Sidhaye V, Hoffert JD, King LS. 2005. cAMP has distinct acute and chronic effects on aquaporin-5 in lung epithelial cells. J Biol Chem. 280(5):3590-3596.