The platelet-derived growth factor (PDGF) family consists of proteins derived from four genes (PDGF-A, -B, -C, and -D) that form four disulfide-linked homodimers (PDGF-AA, -BB, -CC, and -DD) and one heterodimer (PDGF-AB) (1). These proteins regulate diverse cellular functions by binding to and inducing the homo- or hetero-dimerization of two receptor tyrosine kinases (PDGF R alpha  and R beta ). Within the PDGF family, PDGF-C and PDGF-D constitute a subgroup that shares similar structural organization (2, 3). Both proteins are secreted as inactive homodimeric latent growth factors. Each monomer has two distinct protein domains: an N-terminal CUB domain; and a C-terminal PDGF/VEGF homology domain that shares 27 - 35% sequence identity with the corresponding regions of other PDGF family members. An 80 - 90 amino acid residue hinge region connects the two domains. Sequential removal of the CUB domains in the homodimeric latent growth factor by extracellular proteolytic cleavage at the hinge region is required to release the bioactive PDGF/VEGF homology domain (1). Twelve cysteine residues are found within the PDGF/VEGF homology domain of PDGF-C, including the characteristic eight invariant cysteine residues involved in inter- and intra-chains disulfide-bonds needed for the formation of the cysteine-knot structure. Bioactive PDGF-CC binds with high-affinity to PDGF R alpha  but not PDGF R beta  and activates PDGF R alpha homodimerization (1). PDGF-CC has also been shown to activate PDGF R alpha beta heterodimers (1). PDGF-CC is expressed in multiple embryonic and adult cell types and tissues. During embryonic development, PDGF-CC is involved in ductal morphogenesis (4). PDGF-CC is a potent angiogenic factor that stimulates vessel growth in the mouse cornea pocket assay and in the CAM assay (5). It stimulates coronary artery smooth muscle cell proliferation and may play an important role in cardiovascular development and function (6). PDGF-CC is also expressed in many tumors and tumor cell lines and has a causative role in tumorigenesis (7). Mature human and mouse PDGF-C share 93.7% amino acid sequence identity.