Platelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid protein that in humans is encoded by the PDGFCgene.[1][2] Platelet-derived growth factors are important in connective tissue growth, survival and function, and consist of disulphide-linked dimers involving two polypeptide chains, PDGF-A and PDGF-B. PDGF-C is a member of the PDGF/VEGF family of growth factors with a unique two-domain structure and expression pattern. PDGF-C was not previously identified with PDGF-A and PDGF-B, possibly because it may be that it is synthesized and secreted as a latent growth factor, requiring proteolytic removal of the N-terminal CUB domain for receptor binding and activation.[3]
The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a core motif of eight cysteines. This gene product appears to form only homodimers. It differs from the platelet-derived growth factor alpha and beta polypeptides in having an unusual N-terminal domain, the CUB domain.[2]
PDGF-C is a key component of the PDGFR-α signaling pathway and has a specific role in palatogenesis and the morphogenesis of the integumentary tissue. The phenotypes of compound mutants imply that PDGF-C and PDGF-A may function as principal ligands for PDGFR-α.[4]
Mouse knockout studies show that PDGF-C is required for palatogenesis. Although human studies support an etiologic role for several genes in cleft lip and palate etiology (PVRL1, IRF6, and MSX1), expression levels of the mouse homologs of these genes were unaltered in Pdgfc−/− mutant embryos that develop clefts, suggesting that their activity is not related to PDGF-C signaling in palatogenesis, so PDGF-C signaling is a new pathway in palatogenesis.[5]
PDGF-C is a latent growth factor with proteolytic activation, and the processing enzyme might be controlled by the other CLP-associated genes that may indirectly connect to PDGF-C signaling. Notably, a 30-cM region on human chromosome 4, where the PDGFC gene maps, shows strong linkage association with CLP26, and clinical genetic data further suggest a potential link between PDGFC gene polymorphism and cleft lip and palate.[4]
References
↑Hamada T, Ui-Tei K, Miyata Y (June 2000). "A novel gene derived from developing spinal cords, SCDGF, is a unique member of the PDGF/VEGF family". FEBS Lett. 475 (2): 97–102. doi:10.1016/S0014-5793(00)01640-9. PMID10858496.
↑Li X, Pontén A, Aase K, Karlsson L, Abramsson A, Uutela M, Bäckström G, Hellström M, Boström H, Li H, Soriano P, Betsholtz C, Heldin CH, Alitalo K, Ostman A, Eriksson U (May 2000). "PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor". Nat. Cell Biol. 2 (5): 302–9. doi:10.1038/35010579. PMID10806482.
↑ 4.04.1Ding H, Wu X, Boström H, Kim I, Wong N, Tsoi B, O'Rourke M, Koh GY, Soriano P, Betsholtz C, Hart TC, Marazita ML, Field LL, Tam PP, Nagy A (October 2004). "A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling". Nat. Genet. 36 (10): 1111–6. doi:10.1038/ng1415. PMID15361870.
↑Gilbertson DG, Duff ME, West JW, Kelly JD, Sheppard PO, Hofstrand PD, Gao Z, Shoemaker K, Bukowski TR, Moore M, Feldhaus AL, Humes JM, Palmer TE, Hart CE (July 2001). "Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor". J. Biol. Chem. 276 (29): 27406–14. doi:10.1074/jbc.M101056200. PMID11297552.
Further reading
Li X, Pontén A, Aase K, et al. (2000). "PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor". Nat. Cell Biol. 2 (5): 302–9. doi:10.1038/35010579. PMID10806482.
Tsai YJ, Lee RK, Lin SP, Chen YH (2000). "Identification of a novel platelet-derived growth factor-like gene, fallotein, in the human reproductive tract". Biochim. Biophys. Acta. 1492 (1): 196–202. doi:10.1016/s0167-4781(00)00066-x. PMID11004490.
Uutela M, Laurén J, Bergsten E, et al. (2001). "Chromosomal location, exon structure, and vascular expression patterns of the human PDGFC and PDGFC genes". Circulation. 103 (18): 2242–7. doi:10.1161/01.cir.103.18.2242. PMID11342471.
Zwerner JP, May WA (2002). "Dominant negative PDGF-C inhibits growth of Ewing family tumor cell lines". Oncogene. 21 (24): 3847–54. doi:10.1038/sj.onc.1205486. PMID12032822.
Andrae J, Molander C, Smits A, et al. (2002). "Platelet-derived growth factor-B and -C and active alpha-receptors in medulloblastoma cells". Biochem. Biophys. Res. Commun. 296 (3): 604–11. doi:10.1016/S0006-291X(02)00917-8. PMID12176024.
Reigstad LJ, Sande HM, Fluge Ø, et al. (2003). "Platelet-derived growth factor (PDGF)-C, a PDGF family member with a vascular endothelial growth factor-like structure". J. Biol. Chem. 278 (19): 17114–20. doi:10.1074/jbc.M301728200. PMID12598536.
Eitner F, Ostendorf T, Kretzler M, et al. (2003). "PDGF-C expression in the developing and normal adult human kidney and in glomerular diseases". J. Am. Soc. Nephrol. 14 (5): 1145–53. doi:10.1097/01.ASN.0000062964.75006.A8. PMID12707385.
Fang L, Yan Y, Komuves LG, et al. (2004). "PDGF C is a selective alpha platelet-derived growth factor receptor agonist that is highly expressed in platelet alpha granules and vascular smooth muscle". Arterioscler. Thromb. Vasc. Biol. 24 (4): 787–92. doi:10.1161/01.ATV.0000120785.82268.8b. PMID15061151.
Jinnin M, Ihn H, Mimura Y, et al. (2005). "Regulation of fibrogenic/fibrolytic genes by platelet-derived growth factor C, a novel growth factor, in human dermal fibroblasts". J. Cell. Physiol. 202 (2): 510–7. doi:10.1002/jcp.20154. PMID15389578.
Fredriksson L, Ehnman M, Fieber C, Eriksson U (2005). "Structural requirements for activation of latent platelet-derived growth factor CC by tissue plasminogen activator". J. Biol. Chem. 280 (29): 26856–62. doi:10.1074/jbc.M503388200. PMID15911618.
Reigstad LJ, Martinez A, Varhaug JE, Lillehaug JR (2006). "Nuclear localisation of endogenous SUMO-1-modified PDGF-C in human thyroid tissue and cell lines". Exp. Cell Res. 312 (6): 782–95. doi:10.1016/j.yexcr.2005.11.035. PMID16443219.