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David Pearce, MD
Regulation of gene expression and epithelial ion transport by stress steroids
Selected Publications | Complete Publications


phone
(415) 476-7015
email
dpearce@medsfgh.ucsf.edu
additional
websites

none

secondary
research affiliation
Vascular & Cardiac Biology
Regulation of cellular functions by SGK kinases.

Serine-threonine kinases regulate an enormous variety of cellular actions and mediate the effects of numerous hormones. The SGK/Akt family of kinases control cellular ion transport, metabolism and tissue differentiation. There are three SGK and three Akt isoforms, encoded by distinct genes. They all have distinct functions, even though their expression patterns and substrate specificities are overlapping. We are interested in understanding how determinants of cellular localization and interactions with cellular regulators control the physiological actions of these kinases, particularly in regulating epithelial ion transport. Interestingly, SGK1 controls the trafficking of specific ion transporters by phosphorylating and inhibiting the ubiquitin ligase Nedd4-2. Abnormalities in this signaling pathway can result in severe hypertension and electrolyte abnormalities.


Selected Publications

Chen, S-Y, Bhargava, A, Mastroberardino, L, Meijer, OC, Wang, J, Buse, P, Firestone, GL, Verrey, F, and Pearce, D, Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc Natl Acad Sci U S A, 1999. 96 (5): 2514-9.

Wang, J, Barbry, P, Maiyar, AC, Rozansky, DJ, Bhargava, A, Leong, M, Firestone, GL, and Pearce, D, SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport. Am. J. Physiol., 2001. 280 (2): F303-F313.

Debonneville, C, Flores, SY, Kamynina, E, Plant, PJ, Tauxe, C, Thomas, MA, Munster, C, Chraibi, A, Pratt, JH, Horisberger, JD, Pearce, D, Loffing, J, and Staub, O, Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. Embo J, 2001. 20 (24): 7052-9.

McCormick, JA, Feng, Y, Dawson, K, Behne, MJ, Yu, B, Wang, J, Wyatt, AW, Henke, G, Grahammer, F, Mauro, TM, Lang, F, and Pearce, D, Targeted Disruption of the Protein Kinase SGK3/CISK Impairs Postnatal Hair Follicle Development. Mol Biol Cell, 2004. 15 (9): 4278-88.

Bhargava, A and Pearce, D, Mechanisms of mineralocorticoid action: determinants of receptor specificity and actions of regulated gene products. Trends Endocrinol Metab, 2004. 15 (4): 147-53.

information last updated November 2004


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