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. 1997 Nov 13;390(6656):192-6.
doi: 10.1038/36621.

A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate

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A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate

L E Rameh et al. Nature. .

Abstract

Phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2), a key molecule in the phosphoinositide signalling pathway, was thought to be synthesized exclusively by phosphorylation of PtdIns-4-P at the D-5 position of the inositol ring. The enzymes that produce PtdIns-4,5-P2 in vitro fall into two related subfamilies (type I and type II PtdInsP-5-OH kinases, or PIP(5)Ks) based on their enzymatic properties and sequence similarities'. Here we have reinvestigated the substrate specificities of these enzymes. As expected, the type I enzyme phosphorylates PtdIns-4-P at the D-5 position of the inositol ring. Surprisingly, the type II enzyme, which is abundant in some tissues, phosphorylates PtdIns-5-P at the D-4 position, and thus should be considered as a 4-OH kinase, or PIP(4)K. The earlier error in characterizing the activity of the type II enzyme is due to the presence of contaminating PtdIns-5-P in commercial preparations of PtdIns-4-P. Although PtdIns-5-P was previously thought not to exist in vivo, we find evidence for the presence of this lipid in mammalian fibroblasts, establishing a new pathway for PtdIns-4,5-P2 synthesis.

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Comment in

  • Inositol lipid pathways turn turtle.
    Hinchliffe K, Irvine R. Hinchliffe K, et al. Nature. 1997 Nov 13;390(6656):123-4. doi: 10.1038/36458. Nature. 1997. PMID: 9367149 No abstract available.

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