title: R-Spondin proteins: a novel link to beta-catenin activation.
abstract: The R-spondin (Rspo) protein family is a recently described group of four distinct human secreted proteins. Reported activities for Rspo proteins include essential roles in vertebrate development and their ligand-type activities overlap substantially with those of the canonical Wnt ligands in that both Rspo and canonical Wnt signaling result in the activation of beta-catenin. In a general functional screen for human secreted proteins using transgenic mouse models, we identified human R-spondin1 (hRspo1) protein as a potent and specific mitogen for the gastrointestinal epithelium and demonstrated a potential therapeutic application for the protein in mouse models of cancer therapy-induced mucositis. In contrast to previous studies, our data indicated only partial overlap between Wnt and Rspo ligand activities, suggesting that there may be independent receptor/signaling pathways for Rspo proteins that intersect those of Wnt at the level of beta-catenin. Here we summarize the current reported data on the Rspo family and discuss these results in terms of alternate mechanisms of action. We have extended our observations on the potential therapeutic application of Rspo proteins by showing that all four human Rspo family members are capable of inducing epithelial proliferation and report the first non-vertebrate Rspo family member.
authors.affiliation: Nuvelo Inc., San Carlos, California, USA.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Kim
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhao
authors.forename: Susan
authors.initials: S
authors.lastname: Andarmani
authors.forename: Makoto
authors.initials: M
authors.lastname: Kakitani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oshima
authors.forename: Minke E
authors.initials: ME
authors.lastname: Binnerts
authors.forename: Arie
authors.initials: A
authors.lastname: Abo
authors.forename: Kazuma
authors.initials: K
authors.lastname: Tomizuka
authors.forename: Walter D
authors.initials: WD
authors.lastname: Funk
mesh_terms: D000818:Animals; D006801:Humans; D015398:Signal Transduction; D019699:Thrombospondins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D000098907:R-Spondins
chemical_list: D019699:Thrombospondins; D051176:beta Catenin; C503243:RSPO1 protein, human; D000098907:R-Spondins