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Mol Cell Biol, July 1998, p. 3956-3965, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Novel Phosphorylation-Dependent RNase Activity of GAP-SH3 Binding Protein: a Potential Link between Signal Transduction and RNA Stability

Imed-eddine Gallouzi,1 Fabienne Parker,2 Karim Chebli,1 Florence Maurier,2 Emmanuel Labourier,1 Isabelle Barlat,2 Jean-Paul Capony,3 Bruno Tocque,2 and Jamal Tazi1 *

Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Université Montpellier II, F34293 Montpellier Cedex 5,1 Gene Medicine Department, Centre de Recherche de Vitry-Alfortville, Rhône-Poulenc Rorer SA, 94403 Vitry sur Seine,2 and Centre de Recherche de Biochimie Macromoléculaire, CNRS LP 9008-INSERM Unité 249, CNRS, F34293 Montpellier Cedex 1,3 France

Received 26 February 1998/Returned for modification 10 April 1998/Accepted 14 April 1998

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.


* Corresponding author. Mailing address: Institut de Genetique Moleculaire de Montpellier (IGM), UMR 5535 CNRS, Universite Montpellier II CNRS, 1919, route de Mende, F34293 Montpellier Cedex 5, France. Phone: 33 (0) 4 67 61 36 85. Fax: 33 (0) 4 67 04 02 45. E-mail: tazi{at}igm.cnrs-mop.fr.


Mol Cell Biol, July 1998, p. 3956-3965, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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