Inhibition of Neuroblastoma Cell Phosphatidylinositol 3-Kinase by CDP-Diacylglycerol and Phosphatidate |
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Authors: | Yaakov Lavie Bernard W Agranoff |
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Institution: | Neuroscience Laboratory, University of Michigan, Ann Arbor, Michigan, U.S.A. |
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Abstract: | Abstract: Phosphatidylinositol (PI) 3-kinase is activated by a variety of agents, including various growth factors, and has been proposed to play a role in initiation of cell growth, proliferation, and differentiation. We here investigate the effect of various membrane lipids on PI 3-kinase immunopurified from human SH-SY5Y neuroblastoma cells. CDP-diacylglycerol (CDP-DAG) inhibited PI 3-kinase activity with an IC50 of 6 µ M . Phosphatidate (PA) was also inhibitory (IC50 = 38 µ M ) as was lysophosphatidate. Neither DAG nor any of the other phospholipids examined affected PI 3-kinase activity. The results offer the possibility that CDP-DAG or PA at critical membrane sites may exert functionally significant metabolic regulation at the point of convergence of the PI 3-kinase-directed and the PI 4-kinase-directed phosphoinositide signal transduction pathways. |
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Keywords: | Phosphatidylinositol 3-kinase CDP-diacylglycerol Lysophosphatidate Phosphatidate SH-SY5Y neuroblastoma cells |
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