R-Spondin
RSPO1 is a member of the R-spondin family and encodes a secreted activator protein with two cystein-rich, furin-like domains and one thrombospondin type 1 domain. In mice, the protein induces the rapid onset of crypt cell proliferation and increases intestinal epithelial healing, providing a protective effect against chemotherapy-induced adverse effects.R-spondin transcripts were observed mainly in central nervous system (CNS) tissues, especially in association with the roof plate structure, in 10- and 12-dpc embryos. Outside the CNS, R-spondin transcripts were detected in forelimb buds after 10 dpc, especially in the body trunk and the proximal posterior part of the anterior limb bud. Expression was also observed in facial parenchyma surrounding the nasal cavity at 12 dpc.
R-spondins (RSPOs), such as RSPO2, are secreted proteins that regulate beta-catenin (CTNNB1) signaling. Xenopus and human RSPO2 enhanced mouse Wnt3a signaling in transfected human embryonic kidney cells. C-terminally truncated Xenopus Rspo2, but not the full-length protein, was secreted from cells and retained its activity. Mutation analysis showed that the TSP1 domain of Xenopus Rspo2 was dispensable for activity, but the furin domains were required. RT-PCR analysis showed that Xenopus embryos injected with Wnt8 or beta-catenin induced Rspo2 and Rspo3. Overexpression of Rspo2 in Xenopus activated the Wnt/beta-catenin pathway upstream of dishevelled (DVL1), interfered with Tgfb-type growth factors, and promoted myogenesis.
RSPO3 encodes a member of the thrombospondin type 1 repeat supergene family. In addition, the protein contains a furin-like cysteine-rich region. Furin-like repeat domains have been found in a variety of eukaryotic proteins involved in the mechanism of signal transduction by receptor tyrosine kinases.The 272-amino acid protein has an N-terminal cys-rich domain (CRD) and a central thrombospondin type-1 (THBS1) repeat (TSR) domain. Northern blot analysis detected 3.0- and 4.0-kb transcripts in placenta, lung, and skeletal muscle. RT-PCR revealed ubiquitous expression, with highest levels in placenta, small intestine, fetal thymus, and lymph node. RSPO3 expression was detected in all tumor tissues examined except a lung carcinoma and an ovarian carcinoma.
RSPO4 encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants.
The 224-amino acid human RSPO4 protein, like other members of the RSPO family, contains an N-terminal signal peptide, 2 furin-like domains, a thrombospondin type-1 (THBS1) domain, and a C-terminal low-complexity region enriched with positively charged amino acids. Dot blot analysis revealed very weak expression of RSPO4 in adult organs and tumors.
R-spondins (RSPOs), such as RSPO2, are secreted proteins that regulate beta-catenin (CTNNB1) signaling. Xenopus and human RSPO2 enhanced mouse Wnt3a signaling in transfected human embryonic kidney cells. C-terminally truncated Xenopus Rspo2, but not the full-length protein, was secreted from cells and retained its activity. Mutation analysis showed that the TSP1 domain of Xenopus Rspo2 was dispensable for activity, but the furin domains were required. RT-PCR analysis showed that Xenopus embryos injected with Wnt8 or beta-catenin induced Rspo2 and Rspo3. Overexpression of Rspo2 in Xenopus activated the Wnt/beta-catenin pathway upstream of dishevelled (DVL1), interfered with Tgfb-type growth factors, and promoted myogenesis.
RSPO3 encodes a member of the thrombospondin type 1 repeat supergene family. In addition, the protein contains a furin-like cysteine-rich region. Furin-like repeat domains have been found in a variety of eukaryotic proteins involved in the mechanism of signal transduction by receptor tyrosine kinases.The 272-amino acid protein has an N-terminal cys-rich domain (CRD) and a central thrombospondin type-1 (THBS1) repeat (TSR) domain. Northern blot analysis detected 3.0- and 4.0-kb transcripts in placenta, lung, and skeletal muscle. RT-PCR revealed ubiquitous expression, with highest levels in placenta, small intestine, fetal thymus, and lymph node. RSPO3 expression was detected in all tumor tissues examined except a lung carcinoma and an ovarian carcinoma.
RSPO4 encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants.
The 224-amino acid human RSPO4 protein, like other members of the RSPO family, contains an N-terminal signal peptide, 2 furin-like domains, a thrombospondin type-1 (THBS1) domain, and a C-terminal low-complexity region enriched with positively charged amino acids. Dot blot analysis revealed very weak expression of RSPO4 in adult organs and tumors.
