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

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ALTHOUGH the hormone-stimulated synthesis of 3-phosphorylated inositol lipids is known to form an intracellular signalling system 1–5 , 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)P 2 3-OH) kinase. A similar conclusion has been applied to explain the actions of formyl-Met-Leu-Phe on neutrophils 6 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)P 2 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)P 2 3-OH kinase, PtdIns(3,4,5)P 3 , as a possible new second messenger.

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Cell Line Phosphates Phosphotransferases Phosphotransferases (Alcohol Group Acceptor Phosphatidylinositols Phosphatidylinositol Phosphates Platelet-Derived Growth Factor N-Formylmethionine Leucyl-Phenylalanine Signal Transduction Enzyme Activation