Phospholipase Cε is a nexus for Rho and Rap-mediated G protein-coupled receptor-induced astrocyte proliferation

Simona Citro, Sundeep Malik, Emily A. Oestreich, Julie Radeff-Huang, Grant G. Kelley, Alan V. Smrcka, Joan Heller Brown

Research output: Contribution to journalArticle

Abstract

Phospholipase Cε (PLCε) has been suggested to transduce signals from small GTPases, but its biological function has not yet been clarified. Using astrocytes from PLCε-deficient mice, we demonstrate that endogenous G protein-coupled receptors (GPCRs) for lysophosphatidic acid, sphingosine 1-phosphate, and thrombin regulate phosphoinositide hydrolysis primarily through PLCε. Stimulation by lysophospholipids occurs through Gi, whereas thrombin activates PLC through Rho. Further studies reveal that PLCε is required for thrombin- but not LPA-induced sustained ERK activation and DNA synthesis, providing a novel mechanism for GPCR and Rho signaling to cell proliferation. The requirement for PLCε in this pathway can be explained by its role as a guanine nucleotide exchange factor for Rap1. Thus, PLCε serves to transduce mitogenic signals through a mechanism distinct from its role in generation of PLC-derived second messengers.

Original languageEnglish
Pages (from-to)15543-15548
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number39
DOIs
Publication statusPublished - Sep 25 2007

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Keywords

  • Guanine nucleotide exchange factor
  • Lysophospholipids
  • Mitogenesis
  • Small GTpases
  • Thrombin

ASJC Scopus subject areas

  • General
  • Genetics

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