Editors' ChoiceLipid Signaling

Multikinase Acts as Nuclear PI3-Kinase

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Science's STKE  13 Sep 2005:
Vol. 2005, Issue 301, pp. tw326
DOI: 10.1126/stke.3012005tw326

Resnick et al. provide new insight into the biological roles of the enzyme inositol polyphosphate multikinase (IPMK, also called Ipk2). The protein was so named because it phosphorylates multiple sites on water-soluble inositol polyphosphate rings. However, Resnick et al. show that in vitro and in vivo, IPMKs from yeast and mammals have lipid inositol kinase activity. This activity is highly specific for the D-3 position of the inositol ring--even more so than the better known phosphoinositide 3-kinases (PI3Ks), which, in mammals, generate phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] in response to activated receptor tyrosine kinases. Unlike PI3K, though, IPMK was found almost exclusively in the nucleus of transfected yeast or human cells. IPMK had been previously implicated in control of gene expression in yeast, and Resnick et al. used experiments in yeast lacking phospholipase C (which consequently have no highly phosphorylated soluble inositol polyphosphates) to show that transcriptional regulatory activity of IPMK appears to result from its lipid kinase activity. Thus, the authors conclude, PI(3,4,5)P3--once thought to be absent in yeast (which lack receptor tyrosine kinases)--may have important roles in regulation of transcription in evolutionarily primitive eukaryotes, and these roles may well be conserved in mammals.

A. C. Resnick, A. M. Snowman, B. N. Kang, K. J. Hurt, S. H. Snyder, A. Saiardi, Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity. Proc. Natl. Acad. Sci. U.S.A. 102, 12783-12788 (2005). [Abstract] [Full Text]

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