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.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - Sep 25 2007|
- Guanine nucleotide exchange factor
- Small GTpases
ASJC Scopus subject areas