Missense mutations of the ephrin receptor EPHA1 associated with Alzheimer's disease disrupt receptor signaling functions.

ABSTRACT: Missense mutations in the EPHA1 receptor tyrosine kinase have been identified in Alzheimer's patients. To gain insight into their potential role in disease pathogenesis, we investigated the effects of four of these mutations. We show that the P460L mutation in the second fibronectin type III (FN2) domain drastically reduces EPHA1 cell surface localization while increasing tyrosine phosphorylation of the cell surface-localized receptor. The R791H mutation in the kinase domain abolishes EPHA1 tyrosine phosphorylation, indicating abrogation of kinase-dependent signaling. Furthermore, both mutations decrease EPHA1 phosphorylation on S906 in the kinase-SAM linker region, suggesting impairment of a noncanonical form of signaling regulated by serine/threonine kinases. The R492Q mutation, also in

SUBMITTER: Matsumoto M 

PROVIDER: S-EPMC11773478 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature