{
  "abstract": "Protein tyrosine phosphatase sigma (PTPσ) is a member of the leukocyte common antigen-related (LAR) family of receptor-type protein tyrosine phosphatases. Its architecture integrates an extracellular proteoglycan-sensing region, a single-pass transmembrane helix, and tandem intracellular phosphatase domains. In neural injury, inhibition of PTPσ signaling can relieve chondroitin sulfate proteoglycan (CSPG)-mediated restriction of axonal growth and plasticity. In rheumatoid arthritis (RA), by contrast, restoration of PTPσ activity in fibroblast-like synoviocytes can suppress pathogenic migration and invasion. Structural studies have established a proteoglycan-switch model in which glycosaminoglycan engagement of the N-terminal immunoglobulin-like domains and extracellular clustering regulate intracellular phosphatase activity. Recent work demonstrated that antibodies to the membrane-proximal fibronectin type III-like domain 9 (Fn9) can regulate PTPσ oligomerization and syndecan-4 association in rheumatoid arthritis. Structure-guided protein engineering has converted a poorly soluble PTPσ Ig1-Ig2 decoy into developable Fc-fusion variants with substantially improved solubility and expression yield while retaining glycosaminoglycan binding and cell-based activity. This review summarizes the structural basis of PTPσ regulation and evaluates therapeutic modalities and engineering strategies for advancing PTPσ-directed biologics toward clinical candidates.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Bioengineering, College of Engineering, Hanyang University, Seoul 04673, Republic of Korea."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hyunjin Kim",
      "orcid": "0009-0007-0299-4589"
    },
    {
      "affs": [
        0
      ],
      "name": "Seong Eon Ryu",
      "orcid": "0000-0003-3335-326X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3hb0b1gggncxh.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198659",
  "fulltext_url": "https://europepmc.org/articles/PMC13664785",
  "id": "3hb0b1gggncxh",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://europepmc.org/article/MED/42883905",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Tyrosine Phosphatases"
    ]
  ],
  "openalex": "W7214639672",
  "pdf_url": "https://europepmc.org/articles/PMC13664785?pdf=render",
  "pmcid": "PMC13664785",
  "pmid": "42883905",
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3hb0b1gggncxh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42883905",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883905"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Tyrosine Phosphatases",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structure-Based Engineering for PTPσ-Targeted Therapeutic Development.",
  "title_text": "Structure-Based Engineering for PTPσ-Targeted Therapeutic Development.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/3hb0b1gggncxh",
  "venue": "International journal of molecular sciences",
  "versions": []
}