Role of the CDC25 Homology Domain of Phospholipase Cε in Amplification of Rap1-dependent Signaling

Tai Guang Jin, Takaya Satoh, Yanhong Liao, Chunhua Song, Xianlong Gao, Ken Ichi Kariya, Chang Deng Hu, Tohru Kataoka

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Phospholipase Cε (PLCε) is a novel class of phosphoinositide-specific PLC characterized by possession of CDC25 homology and Ras/Rap1-associating domains. We and others have shown that human PLCε is translocated from the cytoplasm to the plasma membrane and activated by direct association with Ras at its Ras/Rap1-associating domain. In addition, translocation to the perinuclear region was induced upon association with Rap1·GTP. However, the function of the CDC25 homology domain remains to be clarified. Here we show that the CDC25 homology domain of PLCε functions as a guanine nucleotide exchange factor for Rap1 but not for any other Ras family GTPases examined including Rap2 and Ha-Ras. Consistent with this, coexpression of full-length PLCε or its N-terminal fragment carrying the CDC25 homology domain causes an increase of the intracellular level of Rap1·GTP. Concurrently, stimulation of the downstream kinases B-Raf and extracellular signal-regulated kinase is observed, whereas the intracellular level of Ras·GTP and Raf-1 kinase activity are unaffected. In wild-type Rap1-overexpressing cells, epidermal growth factor induces translocation of PLCε to the perinuclear compartments such as the Golgi apparatus, which is sustained for at least 20 min. In contrast, PLCε lacking the CDC25 domain translocates to the perinuclear compartments only transiently. Further, the formation of Rap1·GTP upon epidermal growth factor stimulation exhibits a prolonged time course in cells expressing full-length PLCε compared with those expressing PLCε lacking the CDC25 homology domain. These results suggest a pivotal role of the CDC25 homology domain in amplifying Rap1-dependent signal transduction, including the activation of PLCε itself, at specific subcellular locations such as the Golgi apparatus.

Original languageEnglish (US)
Pages (from-to)30301-30307
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number32
DOIs
StatePublished - Aug 10 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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