First Author | Citro S | Year | 2007 |
Journal | Proc Natl Acad Sci U S A | Volume | 104 |
Issue | 39 | Pages | 15543-8 |
PubMed ID | 17878312 | Mgi Jnum | J:125306 |
Mgi Id | MGI:3758148 | Doi | 10.1073/pnas.0702943104 |
Citation | Citro S, et al. (2007) Phospholipase Cepsilon is a nexus for Rho and Rap-mediated G protein-coupled receptor-induced astrocyte proliferation. Proc Natl Acad Sci U S A 104(39):15543-8 |
abstractText | Phospholipase Cepsilon (PLCepsilon) has been suggested to transduce signals from small GTPases, but its biological function has not yet been clarified. Using astrocytes from PLCepsilon-deficient mice, we demonstrate that endogenous G protein-coupled receptors (GPCRs) for lysophosphatidic acid, sphingosine 1-phosphate, and thrombin regulate phosphoinositide hydrolysis primarily through PLCepsilon. Stimulation by lysophospholipids occurs through G(i), whereas thrombin activates PLC through Rho. Further studies reveal that PLCepsilon 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 PLCepsilon in this pathway can be explained by its role as a guanine nucleotide exchange factor for Rap1. Thus, PLCepsilon serves to transduce mitogenic signals through a mechanism distinct from its role in generation of PLC-derived second messengers. |