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. 2025 Apr;599(8):1169-1186.
doi: 10.1002/1873-3468.70018. Epub 2025 Feb 24.

Human PHOSPHO1 exhibits phosphatidylcholine- and phosphatidylethanolamine-phospholipase C activities and interacts with diacylglycerol kinase δ

Chiaki Murakami  1   2 , Kyoko Atsuta-Tsunoda  1 , Sho Inomata  1 , Takuma Kawai  1 , Yasuhisa Hijikata  1 , Kamila Dilimulati  1 , Hiromichi Sakai  3 , Fumio Sakane  1
Affiliations

Human PHOSPHO1 exhibits phosphatidylcholine- and phosphatidylethanolamine-phospholipase C activities and interacts with diacylglycerol kinase δ

Chiaki Murakami et al. FEBS Lett. 2025 Apr.

Abstract

Phosphatidylcholine- and phosphatidylethanolamine-specific phospholipase C (PC-PLC and PE-PLC) activities, which generate diacylglycerol (DG) and are tricyclodecan-9-yl-xanthogenate (D609)-sensitive, have been detected in both the membrane and cytosolic fractions. We have previously demonstrated that sphingomyelin synthase isozymes, which are transmembrane proteins, exhibit PC-/PE-PLC activities. However, mammalian cytosolic PC-PLC and PE-PLC remain unidentified. Here, we demonstrated that phosphatase orphan 1 (PHOSPHO1), a cytosolic protein, exhibits D609-sensitive PC-PLC and PE-PLC activities. Moreover, the overexpression of PHOSPHO1 in HEK293 cells significantly increased the levels of cellular saturated and/or monounsaturated fatty acid-containing DG. Furthermore, DGKδ cosedimented and colocalized with PHOSPHO1. Collectively, these in vitro findings provide, for the first time, a promising candidate for the long-sought cytosolic PC-/PE-PLC, which may act as DG supply enzyme upstream of DGKδ.

Keywords: PHOSPHO1; diacylglycerol kinase; phosphatase orphan‐1; phosphatidylcholine; phosphatidylethanolamine; phospholipase C.

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References

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