Identification and characterization of a membrane receptor that binds to human STC1

Hin Ting Wan, Alice HM Ng, Wang Ka Lee, Feng Shi, Chris Kong Chu Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Stanniocalcin-1 (STC1) is a hypocalcemic hormone originally identified in bony fishes. The mammalian homolog is found to be involved in inflammation and carcinogenesis, among other physiological functions. In this study, we used the TriCEPS-based ligand–receptor methodology to identify the putative binding proteins of human STC1 (hSTC1) in the human leukemia monocytic cell line, ThP-1. LC–MS/MS analysis of peptides from shortlisted hSTC1-binding proteins detected 32 peptides that belong to IGF2/MPRI. Surface plasmon resonance assay demonstrated that hSTC1 binds to immobilized IGF2R/MPRI with high affinity (10–20 nM) and capacity (Rmax 70–100%). The receptor binding data are comparable with those of (CREG) cellular repressor of E1A-stimulated gene a known ligand of IGF2R/MPRI, with Rmax of 75–80% and affinity values of 1–2 nM. The surface plasmon resonance competitive assays showed CREG competed with hSTC1 in binding to IGF2R/MPRI. The biological effects of hSTC1 on ThP-1 cells were demonstrated via IGF2R/MPRI to significantly reduce secreted levels of IL-1β. This is the first study to reveal the high-affinity binding of hSTC1 to the membrane receptor IGF2R/MPRI.

Original languageEnglish
Article numbere202201497
JournalLife Science Alliance
Volume5
Issue number11
Early online date7 Jul 2022
DOIs
Publication statusE-pub ahead of print - 7 Jul 2022

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Health, Toxicology and Mutagenesis
  • Plant Science
  • Ecology

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