Endogenous G Protein-coupled Receptor Kinase 6 Regulates M3 Muscarinic Acetylcholine Receptor Phosphorylation and Desensitization in Human SH-SY5Y Neuroblastoma Cells

Expression of kinase-dead GRK6 reduced M(3) mACh receptor phosphorylation by 50%.

• Blocking the action of GRK6 using a dominant-negative variant significantly inhibited methacholine-stimulated M(3) mACh receptor phosphorylation.
• M(3) mACh receptor-G alpha(q/11) uncoupling was also reduced by 50% in cells expressing the dominant-negative GRK6 compared to controls.
• Agonist-stimulated inositol phosphate accumulation was more sustained in cells with the dominant-negative GRK6 than in control or GRK5-expressing cells.
• The related kinase GRK5 did not affect M(3) mACh receptor phosphorylation or uncoupling.
• These findings suggest that endogenous GRK6 plays a role in M(3) mACh receptor desensitization.

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