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Signal transduction

Inositol lipid pathways turn turtle

Nature volume 390, pages 123–124 (1997)Cite this article

It seems that there are few limits to the number of molecules and biochemical pathways into which evolution has incorporated myo-inositol. The awesome rate of new inositol phosphates identified in the 1980s was succeeded in the 1990s by a more sedate growth in the number of inositol lipids identified following the discovery of 3-phosphorylated inositol lipids (reviewed in ref. 1). Most people would have thought that the roster of these inositol lipids, and their metabolic interrelationships, is now complete. But two papers2,3 elsewhere in this issue tell us that we don't have all the answers yet.

This then begs the question of whether the in vivo substrate of PIP4K is predominantly PtdIns-3-P or PtdIns-5-P. Little is known about cellular PtdIns-5-P levels and how they change when cells are stimulated with, for example, hormones and neurotransmitters, although Rameh and colleagues2 report that resting mouse fibroblasts contain comparable levels of PtdIns-3-P and PtdIns-5-P. They also demonstrate that a small amount of PtdIns-5-P can be generated from the action of the SH2-containing inositol 5-phosphatase on PtdIns-4,5-P2in vitro. But if this is the sole route of PtdIns-5-P production (that is, if there is no PtdIns-5-kinase activity in cells — and we cannot be sure of that yet), then the primary function of PIP4K would seem to be the removal of PtdIns-5-P, rather than the synthesis of PtdIns-4,5-P2.

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Figure 1: Structure of phosphatidylinositol (PtdIns).
Figure 2: Synthesis of inositol phospholipids.

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  1. the Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QJ, UK

    Kath Hinchliffe & Robin Irvine

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  1. Kath Hinchliffe
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  2. Robin Irvine
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Hinchliffe, K., Irvine, R. Inositol lipid pathways turn turtle. Nature 390, 123–124 (1997). https://doi.org/10.1038/36458

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