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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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PNAS 97, 8687-8692
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SIGNAL TRANSDUCTION:Inositol Phosphates in the Nucleus.
T. H. Chi and G. R. Crabtree (2000)
Science 287, 1937-1939
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Biochemical and Functional Characterization of Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinases.
E. B. Ives, J. Nichols, S. R. Wente, and J. D. York (2000)
J. Biol. Chem.
   Abstract »
Protein Kinase C alpha -mediated Negative Feedback Regulation Is Responsible for the Termination of Insulin-like Growth Factor I-induced Activation of Nuclear Phospholipase C beta 1 in Swiss 3T3 Cells.
A. Xu, Y. Wang, L. Y. Xu, and R. S. Gilmour (2001)
J. Biol. Chem. 276, 14980-14986
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Highly saturated endonuclear phosphatidylcholine is synthesised in situ and co-located with CDPcholine pathway enzymes.
A. N. Hunt, G. T. Clark, G. S. Attard, and A. D. Postle (2000)
J. Biol. Chem.
   Abstract »
Overexpression of the inositol phosphatase SopB in human 293 cells stimulates cellular chloride influx and inhibits nuclear mRNA export.
Y. Feng, S. R. Wente, and P. W. Majerus (2001)
PNAS
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Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5-trisphosphate and an inositol pyrophosphate.
A. Saiardi, E. Nagata, H. R. Luo, A. Sawa, X. Luo, A. M. Snowman, and S. H. Snyder (2001)
PNAS 98, 2306-2311
   Abstract »    Full Text »    PDF »
Inositol hexakisphosphate is a physiological signal regulating the K+-inward rectifying conductance in guard cells.
F. Lemtiri-Chlieh, E. A. C. MacRobbie, and C. A. Brearley (2000)
PNAS 97, 8687-8692
   Abstract »    Full Text »    PDF »

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