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Science 2 July 1999:
Vol. 285. no. 5424, pp. 96 - 100
DOI: 10.1126/science.285.5424.96
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Reports

A Phospholipase C-Dependent Inositol Polyphosphate Kinase Pathway Required for Efficient Messenger RNA Export

John D. York, 1* Audrey R. Odom, 1 Robert Murphy, 2 Eric B. Ives, 2 Susan R. Wente 2*

In order to identify additional factors required for nuclear export of messenger RNA, a genetic screen was conducted with a yeast mutant deficient in a factor Gle1p, which associates with the nuclear pore complex (NPC). The three genes identified encode phospholipase C and two potential inositol polyphosphate kinases. Together, these constitute a signaling pathway from phosphatidylinositol 4,5-bisphosphate to inositol hexakisphosphate (IP6). The common downstream effects of mutations in each component were deficiencies in IP6 synthesis and messenger RNA export, indicating a role for IP6 in GLE1 function and messenger RNA export.

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, Box 8228, 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 (J.D.Y.) or swente{at}cellbio.wustl.edu (S.R.W.)

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Phospholipase C Is Involved in Kinetochore Function in Saccharomyces cerevisiae.
H. Lin, J. H. Choi, J. Hasek, N. DeLillo, W. Lou, and A. Vancura (2000)
Mol. Cell. Biol. 20, 3597-3607
   Abstract »    Full Text »
Discovery of Molecular and Catalytic Diversity among Human Diphosphoinositol-Polyphosphate Phosphohydrolases. AN EXPANDING NUDT FAMILY.
J. J. Caffrey, S. T. Safrany, X. Yang, and S. B. Shears (2000)
J. Biol. Chem. 275, 12730-12736
   Abstract »    Full Text »    PDF »
A Role for Nuclear Inositol 1,4,5-Trisphosphate Kinase in Transcriptional Control.
A. R. Odom, A. Stahlberg, S. R. Wente, and J. D. York (2000)
Science 287, 2026-2029
   Abstract »    Full Text »
Site-directed Mutagenesis of Diphosphoinositol Polyphosphate Phosphohydrolase, a Dual Specificity NUDT Enzyme That Attacks Diadenosine Polyphosphates and Diphosphoinositol Polyphosphates.
X. Yang, S. T. Safrany, and S. B. Shears (1999)
J. Biol. Chem. 274, 35434-35440
   Abstract »    Full Text »    PDF »
The Inositol Hexakisphosphate Kinase Family. CATALYTIC FLEXIBILITY AND FUNCTION IN YEAST VACUOLE BIOGENESIS.
A. Saiardi, J. J. Caffrey, S. H. Snyder, and S. B. Shears (2000)
J. Biol. Chem. 275, 24686-24692
   Abstract »    Full Text »    PDF »
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. 275, 36575-36583
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Phosphorylation of a Synaptic Vesicle-associated Protein by an Inositol Hexakisphosphate-regulated Protein Kinase.
J. M. Hilton, M. Plomann, B. Ritter, J. Modregger, H. N. Freeman, J. R. Falck, U. M. Krishna, and A. B. Tobin (2001)
J. Biol. Chem. 276, 16341-16347
   Abstract »    Full Text »    PDF »
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 98, 875-879
   Abstract »    Full Text »    PDF »
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 »
From the Cover: 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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