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Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase.
Nature. 1992 Jul 09; 358(6382):157-9.Nat

Abstract

Although the hormone-stimulated synthesis of 3-phosphorylated inositol lipids is known to form an intracellular signalling system, 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 neutrophils, 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.

Authors+Show Affiliations

Biochemistry Department, AFRC, Babraham, Cambridge, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1319558

Citation

Hawkins, P T., et al. "Platelet-derived Growth Factor Stimulates Synthesis of PtdIns(3,4,5)P3 By Activating a PtdIns(4,5)P2 3-OH Kinase." Nature, vol. 358, no. 6382, 1992, pp. 157-9.
Hawkins PT, Jackson TR, Stephens LR. Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase. Nature. 1992;358(6382):157-9.
Hawkins, P. T., Jackson, T. R., & Stephens, L. R. (1992). Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase. Nature, 358(6382), 157-9.
Hawkins PT, Jackson TR, Stephens LR. Platelet-derived Growth Factor Stimulates Synthesis of PtdIns(3,4,5)P3 By Activating a PtdIns(4,5)P2 3-OH Kinase. Nature. 1992 Jul 9;358(6382):157-9. PubMed PMID: 1319558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase. AU - Hawkins,P T, AU - Jackson,T R, AU - Stephens,L R, PY - 1992/7/9/pubmed PY - 1992/7/9/medline PY - 1992/7/9/entrez SP - 157 EP - 9 JF - Nature JO - Nature VL - 358 IS - 6382 N2 - Although the hormone-stimulated synthesis of 3-phosphorylated inositol lipids is known to form an intracellular signalling system, 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 neutrophils, 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 - 0028-0836 UR - https://www.unboundmedicine.com/medline/citation/1319558/Platelet_derived_growth_factor_stimulates_synthesis_of_PtdIns_345_P3_by_activating_a_PtdIns_45_P2_3_OH_kinase_ L2 - https://doi.org/10.1038/358157a0 DB - PRIME DP - Unbound Medicine ER -