PDGFC

{{Short description|Protein-coding gene in the species Homo sapiens}}

Platelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid protein that in humans is encoded by the PDGFC gene.{{cite journal | vauthors = Hamada T, Ui-Tei K, Miyata Y | title = A novel gene derived from developing spinal cords, SCDGF, is a unique member of the PDGF/VEGF family | journal = FEBS Lett. | volume = 475 | issue = 2 | pages = 97–102 |date=June 2000 | pmid = 10858496 | doi = 10.1016/S0014-5793(00)01640-9| s2cid = 19634520 | doi-access = free }} 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.{{cite journal | vauthors = 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 | title = PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor | journal = Nat. Cell Biol. | volume = 2 | issue = 5 | pages = 302–9 |date=May 2000 | pmid = 10806482 | doi = 10.1038/35010579 | s2cid = 25066476 }}

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.{{cite web | title = Entrez Gene: PDGFC platelet derived growth factor C| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56034}}

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.{{cite journal | vauthors = Ding 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 | title = A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling | journal = Nat. Genet. | volume = 36 | issue = 10 | pages = 1111–6 |date=October 2004 | pmid = 15361870 | doi = 10.1038/ng1415 | doi-access = free }}

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.{{cite journal | vauthors = Choi SJ, Marazita ML, Hart PS, Sulima PP, Field LL, McHenry TG, Govil M, Cooper ME, Letra A, Menezes R, Narayanan S, Mansilla MA, Granjeiro JM, Vieira AR, Lidral AC, Murray JC, Hart TC | title = The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional activity and is associated with CL/P | journal = European Journal of Human Genetics | volume = 17| issue = 11 | pages = 774–84 |date=December 2009| pmid = 19092777 | pmc = 2788748| doi = 10.1038/ejhg.2008.245 }}

Interactions

PDGFC has been shown to interact with PDGFRA.{{cite journal | vauthors = 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 | title = Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor | journal = J. Biol. Chem. | volume = 276 | issue = 29 | pages = 27406–14 |date=July 2001 | pmid = 11297552 | doi = 10.1074/jbc.M101056200 | doi-access = free }}

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.

References

External links

{{UCSC genome browser|PDGFC}}
{{UCSC gene details|PDGFC}}

PDGFC

Function

Interactions

References

Further reading

External links