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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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