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

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.

Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress

“…Recently, several clinicopathological studies have identi ed serum STC2 levels are elevated in patients with HCC, gastric cancer and colorectal cancer, and particularly high serum STC2 levels are associated with poor prognosis 20,50,51,52 , indicating secreted STC2 could perform its biological functions through an endocrine mechanism at organism levels. It has been reported that the cation-independent mannose-6-phosphate receptor/IGF2R interacts with STC1 and may serve as a receptor 53 . Whether STC2 shares the same receptor or uses a different surface protein as a receptor remains to be investigated.…”

Megalin Facilitates the Regulation of Mitochondrial Function by Extracellular Cues

“…[29][30][31] In the mitochondria, megalin is found in association with Sirt3 and Stc1. [29] Stc1 receptors are found at the plasma membrane and inner mitochondrial membrane, [30,32,33] and as discussed above, Stc1 is defined as mitochondrial intracrine. [6] In prior publications, we showed Stc1 upregulates mitochondrial uncoupling proteins (UCPs) [34][35][36][37] and the energy sensor Sirt3 through activation of yet another energy sensor, AMP-activated protein kinase (AMPK).…”