GRK6 phosphorylates IκBα at Ser32/Ser36 and enhances TNF-α-induced inflammation

GRK6 directly phosphorylates IκBα at Ser(32)/Ser(36), which is essential for NF-κB signaling.

• IκBα, a regulator of NF-κB signaling, was identified as a substrate for GRK6.
• The kinase activity of GRK6 is necessary for enhanced NF-κB signaling following TNF-α stimulation.
• Knockout of GRK6 in peritoneal macrophages significantly reduced transcription of inflammatory genes after TNF-α stimulation.
• A bioluminescence resonance energy transfer (BRET) probe was developed to monitor GRK6 activity.
• TNF-α was shown to induce a conformational change in GRK6.

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