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Science 287 (5460): 2026-2029

Copyright © 2000 by the American Association for the Advancement of Science

A Role for Nuclear Inositol 1,4,5-Trisphosphate Kinase in Transcriptional Control

Audrey R. Odom, 1 Alke Stahlberg, 2 Susan R. Wente, 2 John D. York 1*

Phospholipase C and two inositol polyphosphate (IP) kinases constitute a signaling pathway that regulates nuclear messenger RNA export through production of inositol hexakisphosphate (IP6). The inositol 1,4,5-trisphosphate kinase of this pathway in Saccharomyces cerevisiae, designated Ipk2, was found to be identical to Arg82, a regulator of the transcriptional complex ArgR-Mcm1. Synthesis of inositol 1,4,5,6-tetrakisphosphate, but not IP6, was required for gene regulation through ArgR-Mcm1. Thus, the phospholipase C pathway produces multiple IP messengers that modulate distinct nuclear processes. The results reveal a direct mechanism by which activation of IP signaling may control gene expression.

1 Departments of Pharmacology and Cancer Biology and of Biochemistry, Duke University Medical Center, DUMC 3813, Durham, NC 27710, USA.
2 Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA.
*   To whom correspondence should be addressed. E-mail: yorkj{at}acpub.duke.edu

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