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PMID:14712229
| Citation |
Weissman, JT, Ma, JN, Essex, A, Gao, Y and Burstein, ES (2004) G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Oncogene 23:241-9 |
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| Abstract |
Ras proteins mediate the proliferative effects of G-protein-coupled receptors (GPCRs), but the role of Rap proteins in GPCR signaling is unclear. We have developed a novel cellular proliferation assay for examining signal transduction to Rap utilizing Ras-rap chimeras that respond selectively to Rap-specific exchange factors, but which stimulate cellular proliferation through Ras effectors. Both the D1 dopamine receptor (Gs-coupled) and the 5HT1E serotonin receptor (Gi-coupled) mediated cellular proliferation in a Ras/rap chimera-dependent manner. Responses to both receptors were PKA-independent. Both receptors activated Ras/rap and full-length Rap as measured by activation-specific probes. Pertussis toxin blocked Ras/rap-dependent responses to 5HT1E but not D1. Ras/rap-dependent responses to both receptors were insensitive to beta-gamma scavengers. Responses to 5HT1E, but not D1, were sensitive to inhibition by a dominant-negative C3G fragment, by the Src-like kinase inhibitors PP1 and PP2, and by a dominant-negative mutant of Src. Very similar data were obtained for two other Gi-coupled receptors, the D2 dopamine receptor and the alpha2C adrenergic receptor. A constitutively active mutant of Galphai2 also mediated Ras/rap-dependent responses. These data indicate that GPCRs coupled to pertussis-toxin-sensitive G-proteins activate Rap through a Galpha subunit, C3G, and Src-dependent pathway. |
| Links |
PubMed Online version:10.1038/sj.onc.1207014 |
| Keywords |
Animals; Cyclic AMP-Dependent Protein Kinases/physiology; Enzyme Activation; GTP-Binding Protein alpha Subunits, Gi-Go/physiology; GTP-Binding Protein alpha Subunits, Gs/physiology; Mice; NIH 3T3 Cells; Phosphorylation; Receptors, G-Protein-Coupled/physiology; rap GTP-Binding Proteins/metabolism; ras Proteins/physiology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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