Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor

We have characterized platelet-derived growth factor (PDGF) C, a novel grow th factor belonging to the PDGF family. PDGF-C is a multidomain protein wit h the N-terminal region homologous-to the extracellular CUB domain of neuro pilin-1, and the C-terminal region consists of a growth factor domain (GFD) with homology to vascular endothelial growth factor (25%) and PDGF A-chain (23%). A serum-sensitive cleavage site between the two domains allows rele ase of the GFD from the CUE domain. Competition binding and immunoprecipita tion studies on cells bearing both PDGF alpha and beta receptors reveal a h igh affinity binding of recombinant GFD (PDGF-CC) to PDGF receptor-alpha ho modimers and PDGF receptor-alpha/beta heterodimers, PDGF-CC exhibits greate r mitogenic potency than PDGF-AA and comparable or greater mitogenic activi ty than PDGF-AB and PDGF-BB on several mesenchymal cell types. Analysis of PDGF-CC in vivo in a diabetic mouse model of delayed wound healing showed t hat PDGF-CC significantly enhanced repair of a full-thickness skin excision . Together, these studies describe a third member of the PDGF family (PDGF- C) as a potent mitogen for cells of mesenchymal origin in in vitro and in v ivo systems with a binding pattern similar to PDGF-AB.