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

被引:225
作者
Gilbertson, DG [1 ]
Duff, ME [1 ]
West, JW [1 ]
Kelly, JD [1 ]
Sheppard, PO [1 ]
Hofstrand, PD [1 ]
Gao, ZR [1 ]
Shoemaker, K [1 ]
Bukowski, TR [1 ]
Moore, M [1 ]
Feldhaus, AL [1 ]
Humes, JM [1 ]
Palmer, TE [1 ]
Hart, CE [1 ]
机构
[1] ZymoGenet Inst, Seattle, WA 98102 USA
关键词
D O I
10.1074/jbc.M101056200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 CUE domain. Competition binding and immunoprecipitation studies on cells bearing both PDGF alpha and beta receptors reveal a high affinity binding of recombinant GFD (PDGF-CC) to PDGF receptor-alpha homodimers and PDGF receptor-alpha/beta 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.
引用
收藏
页码:27406 / 27414
页数:9
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