PDGFC

Platelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid is_associated_with::protein that in humans is encoded by the PDGFC is_associated_with::gene. 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.

Function
The protein encoded by this gene is a member of the is_associated_with::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 is_associated_with::CUB domain.

PDGF-C is a key component of the PDGFR-α signaling pathway and has a specific role in palatogenesis and the is_associated_with::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.

Mouse knockout studies show that PDGF-C is required for palatogenesis. Although human studies support an etiologic role for several genes in is_associated_with::cleft lip and palate etiology (is_associated_with::PVRL1, is_associated_with::IRF6, and is_associated_with::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.

Interactions
PDGFC has been shown to interact with is_associated_with::PDGFRA.

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.