title: Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor.
abstract: 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 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.
authors: ZymoGenetics Inc., Seattle, Washington 98102, USA. gilbertd@zgi.com
authors: D G
authors: DG
authors: Gilbertson
authors: M E
authors: ME
authors: Duff
authors: J W
authors: JW
authors: West
authors: J D
authors: JD
authors: Kelly
authors: P O
authors: PO
authors: Sheppard
authors: P D
authors: PD
authors: Hofstrand
authors: Z
authors: Z
authors: Gao
authors: K
authors: K
authors: Shoemaker
authors: T R
authors: TR
authors: Bukowski
authors: M
authors: M
authors: Moore
authors: A L
authors: AL
authors: Feldhaus
authors: J M
authors: JM
authors: Humes
authors: T E
authors: TE
authors: Palmer
authors: C E
authors: CE
authors: Hart
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000254:growth & development; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D006801:Humans; D008222:Lymphokines; D051379:Mice; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013936:Thymidine / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D018076:DNA, Complementary; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; C411423:platelet-derived growth factor C; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D013936:Thymidine