Platelet-derived growth factor stimulates synthesis of Ptdlns(3,4,5)P3 by activating a Ptdlns(4,5)P2 3-OH kinase (original) (raw)

Nature volume 358, pages 157–159 (1992)Cite this article

Abstract

ALTHOUGH the hormone-stimulated synthesis of 3-phosphorylated inositol lipids is known to form an intracellular signalling system1–5, there is no consensus on the crucial receptor-regulated event in this pathway and it is still not clear which of the intermediates represent potential output signals. We show here that the key step in the synthesis of 3-phosphorylated inositol lipids in 3T3 cells stimulated by platelet-derived growth factor is the activation of a phosphatidylinositol(4,5)-bisphosphate (3)-hydroxy (PtdIns(4,5)P2 3-OH) kinase. A similar conclusion has been applied to explain the actions of formyl-Met-Leu-Phe on neutrophils6, and it may be that receptors that couple through intrinsic tyrosine kinases or through G proteins stimulate the same step in 3-phosphorylated inositol lipid metabolism. The close parallel between these two mechanisms for the activation of PtdIns(4,5)P2 3-OH kinase and those described for the activation of another key signalling enzyme, phospholipase C (ref. 7), focuses attention on the product of the PtdIns(4,5)P2 3-OH kinase, PtdIns(3,4,5)P3, as a possible new second messenger.

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  1. Biochemistry Department, Institute of Animal Physiology and Genetics Research, AFRC, Babraham, Cambridge, CB2 4AT, UK
    P. T. Hawkins, T. R. Jackson & L. R. Stephens

Authors

  1. P. T. Hawkins
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  2. T. R. Jackson
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  3. L. R. Stephens
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Hawkins, P., Jackson, T. & Stephens, L. Platelet-derived growth factor stimulates synthesis of Ptdlns(3,4,5)P3 by activating a Ptdlns(4,5)P2 3-OH kinase.Nature 358, 157–159 (1992). https://doi.org/10.1038/358157a0

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