Abstract
This study demonstrated that activation of tyrosine kinase of epidermal growth factor receptor (EGFR) induces its association with G protein-coupled receptor kinase 2 (GRK2). Immunoprecipitation experiments showed that EGF stimulation increased GRK2 binding to EGFR complex in HEK293 cells coexpressing EGFR and GRK2. The EGF-induced GRK2-EGFR complex formation was greatly reduced by perturbation of EGFR and Src tyrosine kinase activity. Furthermore, studies with GRK2 mutants showed that neither catalytic activity nor the N-terminal domain of GRK2 was required for EGF-induced GRK2-EGFR complex formation. However, overexpression of Gbetagamma scavengers blocked EGF-induced formation of GRK2-EGFR complex.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cyclic AMP-Dependent Protein Kinases / analysis
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Enzyme Activation
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Epidermal Growth Factor / pharmacology
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Epidermal Growth Factor / physiology
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ErbB Receptors / analysis
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ErbB Receptors / drug effects
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ErbB Receptors / metabolism*
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GTP-Binding Protein beta Subunits / metabolism*
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GTP-Binding Protein gamma Subunits / metabolism*
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Humans
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Immunoprecipitation
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Mutation / genetics
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beta-Adrenergic Receptor Kinases
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src-Family Kinases / metabolism
Substances
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Epidermal Growth Factor
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ErbB Receptors
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src-Family Kinases
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Cyclic AMP-Dependent Protein Kinases
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beta-Adrenergic Receptor Kinases