Regulation of a Novel Human Phospholipase C, PLCε, through Membrane Targeting by Ras

Chunhua Song, Chang Deng Hu, Misa Masago, Ken Ichi Kariya, Yuriko Yamawaki-Kataoka, Mitsushige Shibatohge, Dongmei Wu, Takaya Satoh, Tohru Kataoka

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263 Scopus citations

Abstract

Phosphoinositide-specific phospholipase C (PI-PLC) plays a pivotal role in regulation of intracellular signal transduction from various receptor molecules. More than 10 members of human PI-PLC isoforms have been identified and classified into three classes β, γ, and δ, which are regulated by distinct mechanisms. Here we report identification of a novel class of human PI-PLC, named PLCε, which is characterized by the presence of a Ras-associating domain at its C terminus and a CDC25-like domain at its N terminus. The Ras-associating domain of PLCε specifically binds to the GTP-bound forms of Ha-Ras and Rap1A. The dissociation constant for Ha-Ras is estimated to be approximately 40 nm, comparable with those of other Ras effectors. Co-expression of an activated Ha-Ras mutant with PLCε induces its translocation from the cytosol to the plasma membrane. Upon stimulation with epidermal growth factor, similar translocation of ectopically expressed PLCε is observed, which is inhibited by co-expression of dominant-negative Ha-Ras. Furthermore, using a liposome-based reconstitution assay, it is shown that the phosphatidylinositol 4,5-bisphosphate-hydrolyzing activity of PLCε is stimulated in vitro by Ha-Ras in a GTP-dependent manner. These results indicate that Ras directly regulates phosphoinositide breakdown through membrane targeting of PLCε.

Original languageEnglish (US)
Pages (from-to)2752-2757
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number4
DOIs
StatePublished - Jan 26 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Song, C., Hu, C. D., Masago, M., Kariya, K. I., Yamawaki-Kataoka, Y., Shibatohge, M., Wu, D., Satoh, T., & Kataoka, T. (2001). Regulation of a Novel Human Phospholipase C, PLCε, through Membrane Targeting by Ras. Journal of Biological Chemistry, 276(4), 2752-2757. https://doi.org/10.1074/jbc.M008324200