Platelet-derived Growth Factor C (PDGF-C), a Novel Growth Factor That Binds to PDGF α and β Receptor

• Published in: The Journal of biological chemistry 2001-07, Vol.276 (29), p.27406
• Main Authors: Debra G. Gilbertson, Meghan E. Duff, James W. West, James D. Kelly, Paul O. Sheppard, Philip D. Hofstrand, Zeren Gao, Kimberly Shoemaker, Thomas R. Bukowski, Margaret Moore, Andrew L. Feldhaus, Jacqueline M. Humes, Thomas E. Palmer, Charles E. Hart
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M101056200

We have characterized platelet-derived growth factor (PDGF) C, a novel growth factor belonging to the PDGF family. PDGF-C is a multidomain protein with the N-terminal region homologous to the extracellular CUB domain of neuropilin-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 release of the GFD from the CUB domain. Competition binding and immunoprecipitation studies on cells bearing both PDGF α and β receptors reveal a high affinity binding of recombinant GFD (PDGF-CC) to PDGF receptor-α homodimers and PDGF receptor-α/β heterodimers. PDGF-CC exhibits greater mitogenic potency than PDGF-AA and comparable or greater mitogenic activity 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 that 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 vivo systems with a binding pattern similar to PDGF-AB.