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PNAS 102 (36): 12783-12788

Copyright © 2005 by the National Academy of Sciences.


CELL BIOLOGY

Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity

Adam C. Resnick *, Adele M. Snowman *, Bingnan N. Kang {dagger}, K. Joseph Hurt *, Solomon H. Snyder *, {dagger}, {ddagger}, §, and Adolfo Saiardi * ¶, §

Departments of *Neuroscience, {dagger}Pharmacology, and {ddagger}Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205

Contributed by Solomon H. Snyder, July 21, 2005

Abstract: Phosphatidylinositol 3,4,5-trisphosphate is a major intracellular messenger molecule thought to be formed almost exclusively by cytosolic, wortmannin-inhibited phosphoinositide 3-kinase family members. Inositol polyphosphate multikinase was identified as an enzyme that generates a series of water-soluble inositol phosphates. We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. In yeast, this inositol lipid kinase activity physiologically regulates transcription.

Key Words: lipids • nucleus • wortmannin


Author contributions: A.C.R., B.N.K., S.H.S., and A.S. designed research; A.C.R., A.M.S., B.N.K., K.J.H., and A.S. performed research; A.C.R., B.N.K., S.H.S., and A.S. analyzed data; and A.C.R., S.H.S., and A.S. wrote the paper.

Abbreviations: IP3, inositol 1,4,5-trisphosphate; PI(4,5)P2, inositol phosphatidylinositol 4,5-bisphosphate; PLC, phospholipase C; IPK, inositol polyphosphate kinase; IPMK, inositol polyphosphate multikinase; PI3K, phosphoinositide 3-kinase; PI(3,4,5)P3, phosphatidylinositol 3,4,5-trisphosphate.

Present address: Medical Research Council (MRC) Cell Biology Unit and Laboratory for Molecular Cell Biology, Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.

§ To whom correspondence may be addressed. E-mail: dmcbado{at}ucl.ac.uk or ssnyder{at}jhmi.edu.

© 2005 by The National Academy of Sciences of the USA


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