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Updated: Aug 21, 2026

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
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RAGE phosphorylation by CK2 in human epithelial cell model: Modulation of connexin 43 expression

Karen Coste1,2, Anne-Marie Hesse3, Geoffroy Marceau1,4

  • 1Team "Translational Approach to Epithelial Injury and Repair", iGReD, Université Clermont Auvergne, UMR6293 CNRS-U1103 INSERM, 63001 Clermont-Ferrand Cedex, France.

Iscience
|August 20, 2026
PubMed

Insights

Phosphorylation of the receptor for advanced glycation end products (RAGE) at serine 400 by protein kinase CK2 is crucial for its signaling and transcriptional regulation in response to AGE ligands.

Area of Science:

  • Molecular biology
  • Cellular signaling
  • Biochemistry

Background:

  • The receptor for advanced glycation end products (RAGE) is a key mediator in diseases associated with epithelial dysfunction.
  • RAGE activation is not fully understood as it lacks intrinsic kinase activity and relies on external kinases for phosphorylation.

Purpose of the Study:

  • To elucidate the mechanism of RAGE activation and its role in cellular signaling.
  • To identify the specific kinase responsible for RAGE phosphorylation and its downstream effects.

Main Methods:

  • Utilized an epithelial amniotic cell model (FL cells).
  • Employed mass spectrometry, phosphorylation assays, and microscale thermophoresis.
  • Performed in silico analyses to identify transcription factor binding sites.

Main Results:

  • Demonstrated that the intracellular domain of RAGE binds to the alpha subunit of protein kinase CK2 (CK2α).
  • Identified serine 400 as the critical phosphorylation site on RAGE, mediated by CK2α.
  • Showed that mutation of Serine 400 disrupts downstream signaling, including the phosphorylation of CREB and c-Jun, and alters connexin 43 mRNA expression upon AGE ligand stimulation.

Conclusions:

  • Phosphorylation of RAGE at serine 400 by CK2α is essential for RAGE-mediated signaling.
  • This phosphorylation event is critical for the transcriptional regulation of RAGE targets like connexin 43 in response to AGE ligands.
Keywords:
CK2CX43RAGEepithelial cellsphosphorylation

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