title: Grb2 and its apoptotic isoform Grb3-3 associate with heterogeneous nuclear ribonucleoprotein C, and these interactions are modulated by poly(U) RNA.
abstract: Grb2 is an adaptor molecule comprising one Src homology (SH) 2 and two SH3 domains. This protein has a natural isoform named Grb3-3 with a deletion within the SH2 domain. Numerous evidence points to a functional connection between SH2- and SH3-containing proteins and molecules implicated in RNA biogenesis. In this context, we have examined the binding of Grb2 and Grb3-3 to heterogeneous nuclear ribonucleoprotein (hnRNP) C. By the use of an in vivo genetic approach and through in vitro experiments, we furnish evidence that both Grb2 and Grb3-3 interact with hnRNP C proteins. Subcellular fractionation studies clearly show that Grb2 is partially localized in the nucleus. In addition, coimmunoprecipitation experiments demonstrate that Grb2.hnRNP C complexes exist in intact hematopoietic cells. The carboxyl-terminal SH3 domains of Grb2 and Grb3-3 are primarily responsible for the association with hnRNP C. However, although the proline-rich motif of hnRNP C is involved in the interaction with Grb2, it is not in the binding to Grb3-3. Furthermore, poly(U) RNA inhibits the association of Grb2 with hnRNP C, whereas it enhances the interaction between Grb3-3 and hnRNP C. These findings suggest that the Grb2/Grb3-3-hnRNP C interactions might fulfill different biological functions.
authors.affiliation: Institut Cochin de Génétique Moléculaire, U363 INSERM, Hôpital Cochin, 27 rue du faubourg Saint Jacques, 75014 Paris, France. romero@icgm.cochin.inserm.fr
authors.forename: F
authors.initials: F
authors.lastname: Romero
authors.forename: F
authors.initials: F
authors.lastname: Ramos-Morales
authors.forename: A
authors.initials: A
authors.lastname: Domínguez
authors.forename: R M
authors.initials: RM
authors.lastname: Rios
authors.forename: F
authors.initials: F
authors.lastname: Schweighoffer
authors.forename: B
authors.initials: B
authors.lastname: Tocqué
authors.forename: J A
authors.initials: JA
authors.lastname: Pintor-Toro
authors.forename: S
authors.initials: S
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Tortolero
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D003001:Cloning, Molecular; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011072:Poly U / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D011506:Proteins; D012332:RNA, Heterogeneous Nuclear; D012261:Ribonucleoproteins; D011072:Poly U; D066246:ErbB Receptors