Platelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid
protein that in humans is encoded by the PDGFCgene.[5][6] 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.[7]
Function
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.[6]
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.[8]
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.[9]
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.[8]
^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.
S2CID25066476.
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.
S2CID25066476.
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.
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.
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.
S2CID33954371.
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.