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Title: A novel pathway for the formation of phosphatidylinositol 3,4-bisphosphate. Phosphorylation of phosphatidylinositol 3-monophosphate by phosphatidylinositol-3-monophosphate 4-kinase

Journal Article · · Journal of Biological Chemistry; (USA)
OSTI ID:6213494
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  1. Burroughs Wellcome Co., Research Triangle Park, NC (USA)

Three polyphosphoinositides containing phosphate at the D-3 position of the inositol ring can be generated in vitro by phosphorylation of phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate by a phosphatidylinositol-3-kinase. An alternative pathway for in vivo synthesis of one of these lipids was recently suggested: phosphatidylinositol 3,4-bisphosphate could be produced by phosphorylation of phosphatidylinositol 3-phosphate at the D-4 position of the inositol ring. Here we demonstrate the presence of an enzyme in human platelets that phosphorylates (32P)phosphatidylinositol 3-phosphate to produce (32P)phosphatidylinositol 3,4-bisphosphate. This enzyme is Mg2(+)-dependent and its apparent molecular mass is approximately 150 kDa as estimated by sucrose gradient centrifugation and gel filtration chromatography. Unlike the major phosphatidylinositol-4-kinase in platelets that is stimulated by the detergent Nonidet P-40, the phosphatidylinositol-3-phosphate-4-kinase is inhibited by Nonidet P-40. Both activities are also differentiated by the action of adenosine. The discovery of this new enzyme raises the possibility that multiple pathways exists for generating D-3 phosphorylated phosphoinositides.

OSTI ID:
6213494
Journal Information:
Journal of Biological Chemistry; (USA), Vol. 265:36; ISSN 0021-9258
Country of Publication:
United States
Language:
English