RSPO1/R-spondin-1 Protein, Human (CHO, His)

RSPO1/R-spondin-1 is a potent activator of the Wnt/β-catenin signaling pathway and a secretory glycoprotein belonging to the R-spondin family. RSPO1 homotetramers synergize with LRP5/6 via LGR4/5/6 and activate the Wnt/β-catenin pathway by inhibiting DKK1/Kremen-mediated LRP6 endocytosis. RSPO1 promotes β-catenin nuclear translocation, drives HSC activation in liver fibrosis, inhibits adipocyte thermogenic gene expression, and promotes intestinal epithelial proliferation^[1][2][3][4]. RSPO1/R-spondin-1 Protein, Human (CHO, His) is a recombinant human RSPO1 protein expressed in CHO cells with a C-6*His tag.

1. Protein characteristics of RSPO1/R-spondin-1
RSPO1/R-spondin-1, belonging to the R-Spondin (RSpo) secretory protein family (including RSPO1-4 members), is a potent activator of the Wnt/-catenin signaling pathway^[1]. RSPO1/R-spondin-1 is a disulfide-linked secretory glycoprotein containing an N-terminal signal peptide, two furin-like domains (FR), a thrombin ospondin 1 domain (TSP1) and a C-terminal positively charged region. It binds to heparin sulfate proteoglycans (HSPGs) through electrostatic interactions to anchor the extracellular matrix^[1][3].
The activity of R-spondin-1/RSPO1 depends largely on the presence of classical Wnt ligands and LRP6. Although R-spondin-1/RSPO1 does not directly activate LRP6, it can interfere with DKK1 function, regulate the turnover of LRP5 or LRP6 receptors and amplify Wnt-dependent signaling^[2]. RSPO1/R-spondin-1 inhibits DKK1/Kremen-mediated LRP6 endocytosis, maintains cell surface LRP6 levels, and activates the Wnt/β-catenin pathway. After binding to LGR4/5/6, it releases the ubiquitination and degradation of Wnt receptors by ZNRF3/RNF43, promotes β-catenin nuclear translocation and TCF/LEF-dependent gene transcription^[1][3].

2. Application of RSPO1/R-spondin-1
RSPO1/R-spondin-1 participates in the regulation of liver fibrosis: RSPO1/R-spondin-1 can promote the activation of hepatic stellate cells (HSC), upregulate α-SMA and Collagen-I, and drive fibrosis through the Wnt pathway^[4].
RSPO1/R-spondin-1 inhibits fat metabolism: Wild-type RSPO1 enhances Wnt signaling through LGR4, inhibits adipocyte mitochondrial respiration and the expression of thermogenic genes (UCP1, PGC-1α), while the p.R219W mutation destroys HSPG binding, which leads to abnormal release and aggravates obesity^[3].
RSPO1/R-spondin-1 promotes intestinal epithelial proliferation: RSPO1 promotes the proliferation of intestinal crypt stem cells through the Wnt pathway and repairs mucosal damage^[2].

1.R-Spondin-1 enhances BMP-2-mediated differentiation of MC3T3-E1 cells. The expected ED₅₀ is 1.182 μg/mL.corresponding to a specific activity is 8.46 ×10² units/mg.
2.Measured by its ability to induce Topflash reporter activity in HEK293T human embryonic kidney cells. The ED₅₀ for this effect is 1-10 ng/mL.

• 
  R-Spondin-1 enhances BMP-2-mediated differentiation of MC3T3-E1 cells. The expected ED₅₀ is 1.182 μg/ml.corresponding to a specific activity is  8.46 ×10^2 units/mg.

Human

CHO

C-6*His

Q2MKA7-1 (S21-A263)

284654  [NCBI]

Full Length of Isoform-1 Mature Protein

SRGIKGKRQRRISAEGSQACAKGCELCSEVNGCLKCSPKLFILLERNDIRQVGVCLPSCPPGYFDARNPDMNKCIKCKIEHCEACFSHNFCTKCKEGLYLHKGRCYPACPEGSSAANGTMECSSPAQCEMSEWSPWGPCSKKQQLCGFRRGSEERTRRVLHAPVGDHAACSDTKETRRCTVRRVPCPEGQKRRKGGQGRRENANRNLARKESKEAGAGSRRRKGQQQQQQQGTVGPLTSAGPA

38-43.3 kDa

• 
  Greater than 95% as determined by reducing SDS-PAGE.

Lyophilized powder

Lyophilized after extensive dialysis against PBS, pH 7.4 or PBS,4%Mannitol,pH 7.4.

<0.01 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years from date of receipt. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Binnerts ME, et al. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14700-5.  [Content Brief]

  [2]. Zhao J, et al. Tipping the balance: modulating the Wnt pathway for tissue repair. Trends Biotechnol. 2009 Mar;27(3):131-6.  [Content Brief]

  [3]. Sun Y, et al. Human RSPO1 Mutation Represses Beige Adipocyte Thermogenesis and Contributes to Diet-Induced Adiposity. Adv Sci (Weinh). 2023 Apr;10(12):e2207152.  [Content Brief]

  [4]. Yin X, et al. RSPOs facilitated HSC activation and promoted hepatic fibrogenesis. Oncotarget. 2016 Sep 27;7(39):63767-63778.  [Content Brief]

  [5]. Silvano S, et al. RSPO1, a potent inducer of pancreatic β cell neogenesis. Cell Rep Med. 2025 May 20;6(5):102126.  [Content Brief]