GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation.
Beta1-adrenergic receptors, expressed at high levels in the human heart, have a carboxyl-terminal ESKV motif that can directly interact with PDZ domain-containing proteins. Using the beta1-adrenergic receptor carboxyl terminus as bait, we identified the novel beta1-adrenergic receptor-binding partner GIPC in a yeast two-hybrid screen of a human heart cDNA library. ... Here we demonstrate that the PDZ domain-containing protein, GIPC, co-immunoprecipitates with the beta1-adrenergic receptor in COS-7 cells. Essential for this interaction is the Ser residue of the beta1-adrenergic receptor carboxyl-terminal ESKV motif. Our data also demonstrate that beta1-adrenergic receptor stimulation activates the mitogen-activated protein kinase, ERK1/2. beta1-adrenergic receptor-mediated ERK1/2 activation was inhibited by pertussis toxin, implicating Gi, and was substantially decreased by the expression of GIPC. Expression of GIPC had no observable effect on beta1-adrenergic receptor sequestration or receptor-mediated cAMP accumulation. This GIPC effect was specific for the beta1-adrenergic receptor and was dependent on an intact PDZ binding motif. These data suggest that GIPC can regulate beta1-adrenergic receptor-stimulated, Gi-mediated, ERK activation while having no effect on receptor internalization or Gs-mediated cAMP signaling.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, COS Cells, Carrier Proteins, Cell Line, Cyclic AMP, DNA, Complementary, Dose-Response Relationship, Drug, Enzyme Activation, Gene Expression Regulation, Enzymologic, Gene Library, Humans, Immunoblotting, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Myocardium, Neuropeptides, Phosphorylation, Plasmids, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Receptors, Adrenergic, beta-1, Serine, Signal Transduction, Time Factors, Transfection, Two-Hybrid System Techniques
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, COS Cells, Carrier Proteins, Cell Line, Cyclic AMP, DNA, Complementary, Dose-Response Relationship, Drug, Enzyme Activation, Gene Expression Regulation, Enzymologic, Gene Library, Humans, Immunoblotting, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Myocardium, Neuropeptides, Phosphorylation, Plasmids, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Receptors, Adrenergic, beta-1, Serine, Signal Transduction, Time Factors, Transfection, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Jul. 11, 2003
PubMed ID: 12724327
View in: Pubmed Google Scholar
Download Curated Data For This Publication
1106
Switch View:
- Interactions 2