Role of Serine/Threonine Protein Kinase in ADPKD

Mount Sinai School Of Medicine Of Nyu, New York NY

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Abstract

The long term goal of this project is to fully define the function and role of PRKX protein kmase in normal renal development and in PKD mutants. Using a degenerate PCR cloning strategy and library screening techniques, I identified the full length PRKX gene from a human fetal kidney library. Since its distribution patterns are developmentally regulated and differ in ADPKD and ARPKD versus normal kidneys, this has led us to the hypothesis that PRKX kinase is important for the regulation and signal transduction of the PKDl-encoded protein, polycystin-1. Our preliminary studies also suggest that PRKX is bona fide cAMP-responsive kinase that signal to the nucleus via CREB proteins to stimulate gene transcription via CRE elements. In vitro phosphorylation study showed that PRKX fusion protein can phosphorylate PKD 1 C terminal domain. Our hypothesis, therefore is that PRKX protein kinase -is responsible for serine phosphorylation of polycystin-1 protein and that this has important consequences for the regulation of appropriate signal transduction and gene transcription.