In an attempt to elucidate the physiological function(s) of the Ras-related Rap proteins, we used the yeast two-hybrid system and isolated a cDNA encoding a protein that interacts with both Rap1 and Rap2, but not with Ras; the use of Rap2 mutants showed that this interaction is characteristic of a potential Rap effector. This protein was identified as RGS14, a member of the recently discovered family of RGS (‘regulators of G-protein signalling’) proteins that stimulate the GTPase activity of the GTP-binding α subunit of heterotrimeric G-proteins (Gα). Deletion analysis, as well as in vitro binding experiments, revealed that RGS14 binds Rap proteins through a domain distinct from that carrying the RGS identity, and that this domain shares sequence identity with the Ras/Rap binding domain of B-Raf and Raf-1 kinases. RGS14 is distinguished from other RGS proteins by its marked preference for Gαo over other Gα subunits: RGS14 binds preferentially to Gαo in isolated brain membranes, and also interacts preferentially with Gαo (as compared with Gαi1) to stimulate its GTPase activity. In adult mice, RGS14 expression is restricted to spleen and brain. In situ hybridization studies showed that it is highly expressed only in certain areas of mouse brain (such as the CA1 and CA2 regions of the hippocampus), and that this pattern closely resembles that of Rap2, but not Rap1, expression. Double in situ hybridization experiments revealed that certain cells in the hippocampus express both RGS14 and Gαo, as well as both RGS14 and Rap2, showing that the interaction of RGS14 with Gαo and Rap2 is physiologically possible. Taken together, these results suggest that RGS14 could constitute a bridging molecule that allows cross-regulation of signalling pathways downstream from G-protein-coupled receptors involving heterotrimeric proteins of the Gi/o family and those involving the Ras-related GTPase Rap2.
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August 2000
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Research Article|
August 09 2000
RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of Gαo
Sabine TRAVER;
Sabine TRAVER
1
*INSERM U-528, Institut Curie – Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France
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Carole BIDOT;
Carole BIDOT
1
*INSERM U-528, Institut Curie – Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France
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Nathalie SPASSKY;
Nathalie SPASSKY
†INSERM U-495, Hôpital de la Salpêtrière, 75651 Paris Cedex 13, France
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Tania BALTAUSS;
Tania BALTAUSS
2
*INSERM U-528, Institut Curie – Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France
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Marie-France DE TAND;
Marie-France DE TAND
*INSERM U-528, Institut Curie – Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France
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Jean-Léon THOMAS;
Jean-Léon THOMAS
†INSERM U-495, Hôpital de la Salpêtrière, 75651 Paris Cedex 13, France
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Bernard ZALC;
Bernard ZALC
†INSERM U-495, Hôpital de la Salpêtrière, 75651 Paris Cedex 13, France
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Isabelle JANOUEIX-LEROSEY;
Isabelle JANOUEIX-LEROSEY
*INSERM U-528, Institut Curie – Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France
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Jean DE GUNZBURG
Jean DE GUNZBURG
3
*INSERM U-528, Institut Curie – Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France
3To whom correspondence should be addressed (e-mail gunzburg@curie.fr).
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Publisher: Portland Press Ltd
Received:
October 08 1999
Revision Received:
April 18 2000
Accepted:
June 02 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 350 (1): 19–29.
Article history
Received:
October 08 1999
Revision Received:
April 18 2000
Accepted:
June 02 2000
Connected Content
A correction has been published:
RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of Gαo
Citation
Sabine TRAVER, Carole BIDOT, Nathalie SPASSKY, Tania BALTAUSS, Marie-France DE TAND, Jean-Léon THOMAS, Bernard ZALC, Isabelle JANOUEIX-LEROSEY, Jean DE GUNZBURG; RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of Gαo. Biochem J 15 August 2000; 350 (1): 19–29. doi: https://doi.org/10.1042/bj3500019
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