title: Phospholipase Cepsilon is a nexus for Rho and Rap-mediated G protein-coupled receptor-induced astrocyte proliferation.
abstract: 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.
authors: Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA.
authors: Simona
authors: S
authors: Citro
authors: Sundeep
authors: S
authors: Malik
authors: Emily A
authors: EA
authors: Oestreich
authors: Julie
authors: J
authors: Radeff-Huang
authors: Grant G
authors: GG
authors: Kelley
authors: Alan V
authors: AV
authors: Smrcka
authors: Joan Heller
authors: JH
authors: Brown
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D049109:Cell Proliferation; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005838:Genotype; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054801:Phosphoinositide Phospholipase C; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000502:physiology*; D020668:rap GTP-Binding Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D002217:Carbachol; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon; D020558:GTP Phosphohydrolases; D020668:rap GTP-Binding Proteins; D020741:rho GTP-Binding Proteins