Activation of phospholipase C causes increased production of inositol 1,4,5-trisphosphate (IP3), a second messenger that regulates release of Ca2+ from intracellular stores. IP3 can be modified by further phosphorylation, but the signaling role, if any, of such molecules is unclear. Odom et al. report that in Saccharomyces cerevisiae, an IP3 kinase, designated Ipk2p for inositol polyphosphate kinase, that can convert IP3 to IP5 is identical to Arg82p, a protein that participates in regulation of transcription. Arg82p functions as part of a transcriptional complex that controls the response to changes in the extracellular concentration of arginine. Ipk2p protein, but not its kinase activity, was required for proper formation of complexes on DNA promoter elements. However, activity of the enzyme and formation of I(1,4,5,6)-P4 was required for proper transcriptional regulation in response to extracellular arginine. Thus, signaling through inositol polyphosphates appears to be intimately associated with regulation of transcription in the nucleus. In a related Perspective, Chi and Crabtree discuss in greater detail the role of Ipk2p in transcriptional regulation.
Chi, T.H., and Crabtree, G.R. (2000) Signal transduction: Inositol phosphates in the nucleus. Science 287: 1937-1939. [Full Text]