RGS4 inhibits Gq-mediated activation of mitogen-activated protein kinase and phosphoinositide synthesis
Recombinant regulators of G protein-signaling (RGS) proteins stimulate hydrolysis of GTP by alpha subunits of the Gi family but have not been reported to regulate other G protein alpha subunits. Expression of recombinant RGS proteins in cultured cells inhibits Gi-mediated hormonal signals probably by acting as GTPase-activating proteins for Galphai subunits. To ask whether an RGS protein can also regulate cellular responses mediated by G proteins in the Gq/11 family, we compared activation of mitogen-activated protein kinase (MAPK) by a Gq/11-coupled receptor, the bombesin receptor (BR), and a Gi-coupled receptor, the D2 dopamine receptor, transiently co-expressed with or without recombinant RGS4 in COS-7 cells. Pertussis toxin, which uncouples Gi from receptors, blocked MAPK activation by the D2 dopamine receptor but not by the BR. Co-expression of RGS4, however, inhibited activation of MAPK by both receptors causing a rightward shift of the concentration-effect curve for both receptor agonists. RGS4 also inhibited BR-stimulated synthesis of inositol phosphates by an effector target of Gq/11, phospholipase C. Moreover, RGS4 inhibited inositol phosphate synthesis activated by addition of AlF4- to cells overexpressing recombinant alphaq, probably by binding to alphaq.GDP.AlF4-. These results demonstrate that RGS4 can regulate Gq/11-mediated cellular signals by competing for effector binding as well as by acting as a GTPase-activating protein.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1997 |
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| Erschienen: |
1997 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:272 |
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| Enthalten in: |
The Journal of biological chemistry - 272(1997), 18 vom: 02. Mai, Seite 11924-7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yan, Y [VerfasserIn] |
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| Anmerkungen: |
Date Completed 02.06.1997 Date Revised 09.02.2021 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM090711726 |
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| 041 | |a eng | ||
| 100 | 1 | |a Yan, Y |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a RGS4 inhibits Gq-mediated activation of mitogen-activated protein kinase and phosphoinositide synthesis |
| 264 | 1 | |c 1997 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 02.06.1997 | ||
| 500 | |a Date Revised 09.02.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Recombinant regulators of G protein-signaling (RGS) proteins stimulate hydrolysis of GTP by alpha subunits of the Gi family but have not been reported to regulate other G protein alpha subunits. Expression of recombinant RGS proteins in cultured cells inhibits Gi-mediated hormonal signals probably by acting as GTPase-activating proteins for Galphai subunits. To ask whether an RGS protein can also regulate cellular responses mediated by G proteins in the Gq/11 family, we compared activation of mitogen-activated protein kinase (MAPK) by a Gq/11-coupled receptor, the bombesin receptor (BR), and a Gi-coupled receptor, the D2 dopamine receptor, transiently co-expressed with or without recombinant RGS4 in COS-7 cells. Pertussis toxin, which uncouples Gi from receptors, blocked MAPK activation by the D2 dopamine receptor but not by the BR. Co-expression of RGS4, however, inhibited activation of MAPK by both receptors causing a rightward shift of the concentration-effect curve for both receptor agonists. RGS4 also inhibited BR-stimulated synthesis of inositol phosphates by an effector target of Gq/11, phospholipase C. Moreover, RGS4 inhibited inositol phosphate synthesis activated by addition of AlF4- to cells overexpressing recombinant alphaq, probably by binding to alphaq.GDP.AlF4-. These results demonstrate that RGS4 can regulate Gq/11-mediated cellular signals by competing for effector binding as well as by acting as a GTPase-activating protein | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Aluminum Compounds |2 NLM | |
| 650 | 7 | |a Inositol Phosphates |2 NLM | |
| 650 | 7 | |a Phosphatidylinositols |2 NLM | |
| 650 | 7 | |a Proteins |2 NLM | |
| 650 | 7 | |a RGS Proteins |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Virulence Factors, Bordetella |2 NLM | |
| 650 | 7 | |a RGS4 protein |2 NLM | |
| 650 | 7 | |a 175335-35-0 |2 NLM | |
| 650 | 7 | |a Quinpirole |2 NLM | |
| 650 | 7 | |a 20OP60125T |2 NLM | |
| 650 | 7 | |a tetrafluoroaluminate |2 NLM | |
| 650 | 7 | |a 21340-02-3 |2 NLM | |
| 650 | 7 | |a Pertussis Toxin |2 NLM | |
| 650 | 7 | |a EC 2.4.2.31 |2 NLM | |
| 650 | 7 | |a Calcium-Calmodulin-Dependent Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.17 |2 NLM | |
| 650 | 7 | |a GTP-Binding Proteins |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
| 650 | 7 | |a Bombesin |2 NLM | |
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| 650 | 7 | |a Fluorides |2 NLM | |
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| 700 | 1 | |a Chi, P P |e verfasserin |4 aut | |
| 700 | 1 | |a Bourne, H R |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of biological chemistry |d 1945 |g 272(1997), 18 vom: 02. Mai, Seite 11924-7 |w (DE-627)NLM000004995 |x 1083-351X |7 nnns |
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