title: A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: a potential link between signal transduction and RNA stability.
abstract: A potential p120 GTPase-activating protein (RasGAP) effector, G3BP (RasGAP Src homology 3 [SH3] binding protein), was previously identified based on its ability to bind the SH3 domain of RasGAP. Here we show that G3BP colocalizes and physically interacts with RasGAP at the plasma membrane of serum-stimulated but not quiescent Chinese hamster lung fibroblasts. In quiescent cells, G3BP was hyperphosphorylated on serine residues, and this modification was essential for its activity. Indeed, G3BP harbors a phosphorylation-dependent RNase activity which specifically cleaves the 3'-untranslated region of human c-myc mRNA. The endoribonuclease activity of G3BP can initiate mRNA degradation and therefore represents a link between a RasGAP-mediated signaling pathway and RNA turnover.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Université Montpellier II, F34293 Montpellier Cedex 5, France.
authors.forename: I E
authors.initials: IE
authors.lastname: Gallouzi
authors.forename: F
authors.initials: F
authors.lastname: Parker
authors.forename: K
authors.initials: K
authors.lastname: Chebli
authors.forename: F
authors.initials: F
authors.lastname: Maurier
authors.forename: E
authors.initials: E
authors.lastname: Labourier
authors.forename: I
authors.initials: I
authors.lastname: Barlat
authors.forename: J P
authors.initials: JP
authors.lastname: Capony
authors.forename: B
authors.initials: B
authors.lastname: Tocque
authors.forename: J
authors.initials: J
authors.lastname: Tazi
mesh_terms: D000818:Animals; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D020690:GTPase-Activating Proteins; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012313:RNA / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020690:GTPase-Activating Proteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D012694:Serine; D012313:RNA; D012260:Ribonucleases