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TY - JOUR AU - Hawkins, P. T. AU - Jackson, T. R. AU - Stephens, L. R. PY - 1992 DA - 1992/07/01 TI - Platelet-derived growth factor stimulates synthesis of Ptdlns(3,4,5)P3 by activating a Ptdlns(4,5)P2 3-OH kinase JO - Nature SP - 157 EP - 159 VL - 358 IS - 6382 AB - 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. SN - 1476-4687 UR - https://doi.org/10.1038/358157a0 DO - 10.1038/358157a0 ID - Hawkins1992 ER -