Recombinant Mouse DAN Protein

DAN (differential screening-selected gene aberrative in neuroblastoma) was initially identified as a gene whose expression is downregulated in src-transformed rat fibroblasts. DAN has now been shown to be a prototypical member of the DAN family of secreted glycoproteins that are putative BMP antagonists. DAN family members share a cysteine-rich domain that is structurally related to the cysteine-knot motif found in TGF-beta superfamily ligands. There are at least five mouse DAN family members, including DAN, Gremlin/DRM, Cer1 (Cerberus-related), Dante and PRDC (protein related to DAN and cerberus). Additional DAN family members include Xenopus Cerberus, chick Caronte, and C. elegans CeCan 1. Murine DAN binds BMP-2 in immunoprecipitation experiments and acts as a BMP antagonist in Xenopus animal cap explants. The DAN family of proteins are thought to act as antagonists by binding BMP ligands and preventing their interactions with signaling receptor complexes. Recombinant mouse DAN preparations from R&D Systems have been shown to bind BMP-4 in a functional ELISA. It is likely the various DAN family members and other TGF-beta BMP antagonists including Noggin, Chordin, Follistatin, and TSG can selectively antagonize the activities of different subsets of TGF-beta superfamily ligands. These antagonists represent one of the many elaborate regulatory mechanisms that have evolved to control the bioactivities of the TGF-beta superfamily ligands.