Recombinant Mouse PRDC/GREM2 Protein

PRDC (protein related to DAN and Cerberus) is a secreted cysteine knot-containing BMP antagonist belonging to the Cerberus/DAN (CAN) family. Mammalian CAN family members, including Gremlin, Dan, Cerberus, COCO, SOST, and USAG-1, have the conserved 6 cysteine residues that form a cysteine knot, and two additional cysteine residues located in the loops of the cysteine knot, which form an additional intrasubunit disulfide bond (1, 2). Some members of this family, including PRDC, have an additional cysteine residue used for dimerization (1, 2). Of all the CAN family members, PRDC is most closely related to Gremlin, displaying 52% amino acid sequence identity. PRDC was first identified in a screen for developmentally regulated genes by gene trapping in embryonic stem cells (3). PRDC expression is detected by in situ hybridization in the dorsal edge of the spinal cord at E10.5, in commissural neurons in the caudal part of the spinal cord two days later (3), and in the granulosa cells of selective ovarian follicles (4). In the adult, abundant levels of PRDC are detected by RT-PCR in the mouse ovary, brain, and spleen, and to a lesser degree in the colon, kidney, lung, liver, and uterus (4). PRDC acts as a specific BMP antagonist, binding to and blocking signaling induced by BMP-2 or -4, but not Activin or TGF-beta (4). Thus, PRDC expression in the ovary could be involved in follicular development by antagonizing the inhibitory effects of BMPs on FSH stimulation of progesterone (4).