Modulation of the PTPRS proteoglycan switch by antibodies binding to the membrane-proximal fibronectin-type III domain.

ABSTRACT: Protein tyrosine phosphatases (PTPs) receptor type II A (R2A) are negatively regulated through oligomerization upon binding of their extracellular domains to glycosaminoglycans (GAGs) on heparan sulfate proteoglycans (HSPGs). Inactivation of receptor PTP sigma (PTPRS) by HSPGs promotes the aggressive behavior of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Blocking the binding of its N-terminal, membrane-distal immunoglobulin-like 1 and 2 (Ig1&2) domains to its GAG ligands on the HSPG syndecan-4 (SDC4) promotes PTPRS activity and reverses the pathogenic phenotype of FLS. The potential for therapeutically leveraging other PTPRS ectodomain regions is, however, unknown. We show targeting the membrane-proximal fibronectin type III-like 9 (Fn9) domain offers a novel avenue t

SUBMITTER: Hein Da Rosa T 

PROVIDER: S-EPMC12363564 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature