N-glycoproteomics of CHO cell-expressed FGFR3

ABSTRACT: Receptor tyrosine kinases (RTKs) that undergo N-linked glycosylation undergo protein quality control in the endoplasmic reticulum (ER) and subsequently transfer to the Golgi apparatus, where they acquire a diverse array of glycan structures. The family of receptor tyrosine kinases (RTKs) known as FGFR (Fibroblast Growth Factor Receptor) possesses N-glycosylation potential sites within their extracellular domains. Mutations in the modification site of FGFR3 have been documented in conditions such as Achondroplasia (ACH) and hypochondroplasia (HCH). While it is believed that ACH and HCH are associated with the overactivity of FGFR3 and accumulation in the ER, there has yet to be a case where the root cause has been explained from the perspective of glycosylation. This study furnishes a site-specific profile of N-glycans on FGFR3 through structural analysis of the extracellular domain of FGFR3 containing N-glycosylation potential sites, conducted via nLC-MS/MS. Moreover, we generated mutants of FGFR3 with a single glycan deficiency at each site and examined the impact of N-glycans at these sites on the receptor. The findings demonstrated reduced phosphorylation in the N98 glycosylation deficient mutant and accumulation in the ER in the N262 glycosylation deficient mutant, indicating ligand-independent autophosphorylation of the receptor. Hence, it is proposed that N-glycans in FGFR3 may play a role in functional regulation, offering fresh perspectives on disease etiology from a glycosylation standpoint.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Achondroplasia

SUBMITTER: Naoki Fujitani  

LAB HEAD: Motoko Takahashi

PROVIDER: PXD047309 | Pride | 2026-08-05

REPOSITORIES: Pride