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- W4294242534 abstract "Phospholipase C (PLC) β1 hydrolyzes 1-stearoyl-2-arachidonoyl (18:0/20:4)-phosphatidylinositol (PtdIns) 4,5-bisphosphate to produce diacylglycerol, which is converted to phosphatidic acid (PtdOH), in the PtdIns cycle and plays pivotal roles in intracellular signal transduction. The present study identified PLCβ1 as a PtdOH-binding protein using PtdOH-containing liposomes. Moreover, the comparison of the binding of PLCβ1 to various PtdOH species, including 14:0/14:0-PtdOH, 16:0/16:0-PtdOH, 16:0/18:1-PtdOH, 18:0/18:1-PtdOH, 18:0/18:0-PtdOH, 18:1/18:1-PtdOH, 18:0/20:4-PtdOH, and 18:0/22:6-PtdOH, indicated that the interaction of PLCβ1 with 16:0/16:0-PtdOH was the strongest. The PLCβ1-binding activity of 18:0/18:0-PtdOH was almost the same as the binding activity of 16:0/16:0-PtdOH. Furthermore, the binding of PLCβ1 to 16:0/16:0-PtdOH was substantially stronger than 16:0/16:0-phosphatidylserine, 16:0/16:0/16:0/16:0-cardiolipin, 16:0/16:0-PtdIns, and 18:0/20:4-PtdIns. We revealed that a PLCβ1 mutant whose Lys946 and Lys951 residues were replaced with Glu (PLCβ1-KE) did not interact with 16:0/16:0-PtdOH and failed to localize to the plasma membrane in Neuro-2a cells. Retinoic acid-dependent increase in neurite length and numbers was significantly inhibited in PLCβ1-expressing cells; however, this considerable attenuation was not detected in the cells expressing PLCβ1-KE. Overall, these results strongly suggest that PtdOHs containing only saturated fatty acids, including 16:0/16:0-PtdOH, which are not derived from the PtdIns cycle, selectively bind to PLCβ1 and regulate its function." @default.
- W4294242534 created "2022-09-02" @default.
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- W4294242534 date "2022-09-02" @default.
- W4294242534 modified "2023-10-17" @default.
- W4294242534 title "Phosphatidylinositol 4,5‐bisphosphate‐specific phospholipase C β1 selectively binds dipalmitoyl and distearoyl phosphatidic acids via Lys946 and Lys951" @default.
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- W4294242534 doi "https://doi.org/10.1002/lipd.12356" @default.
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