A Specific RAGE Phosphorylation by CK2 in human Amniotic Epithelial cell model

ABSTRACT: The receptor for advanced glycation end products (RAGE) is a multiligand, immunoglobulin-like transmembrane protein expressed in various cell types and implicated in a broad spectrum of diseases linked with epithelial dysfunctions. Despite significant progress in structural studies, the details of its activation mechanism remain poorly understood. Since RAGE lacks intrinsic kinase activity, its activation by phosphorylation depends on the action of intracellular kinases. In a model of epithelial amniotic cell line FL, mass spectrometry analyses combined with in vitro phosphorylation assays and Microscale thermophoresis reveal that the intracytoplasmic domain of RAGE interacts with the CK2 catalytic subunit of protein kinase CK2, leading to the phosphorylation of Serine 400. Structure-function analyses show that the Ser400Ala mutation does not alter the affinity of CK2α for RAGE but causes dysregulation of intracellular kinase signaling pathways, particularly affecting the phosphorylation of the transcription factors CREB (Serine 133) and c-Jun (Serine 63) in the presence of AGE ligands. In silico analyses identified binding sites for these two transcription factors in the Connexin-43 promoter/UTR, a RAGE target gene, and were associated with the overexpression of its mRNA. Our findings suggest that phosphorylation at Serine 400 plays a crucial role in the RAGE signaling in response to AGEs ligands.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Disease Free

SUBMITTER: Hesse Anne-Marie  

LAB HEAD: Yohann Couté

PROVIDER: PXD064008 | Pride | 2026-09-14

REPOSITORIES: Pride