PDGFC

PDGFC
Platelet derived growth factor C
Identifiers
Symbols PDGFC; FALLOTEIN; SCDGF
External IDs OMIM608452 MGI1859631 HomoloGene9423 GeneCards: PDGFC Gene
RNA expression pattern
PBB GE PDGFC 218718 at tn.png
PBB GE PDGFC gnf1h09218 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 56034 54635
Ensembl ENSG00000145431 ENSMUSG00000028019
UniProt Q9NRA1 Q8CI19
RefSeq (mRNA) NM_016205.2 NM_019971.2
RefSeq (protein) NP_057289 NP_064355.1
Location (UCSC) Chr 4:
157.68 – 157.89 Mb
Chr 3:
80.84 – 81.02 Mb
PubMed search [1] [2]

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.[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]

Contents

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.[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 CL/P 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]

File:Genome chart.gif

Interactions

PDGFC has been shown to interact with PDGFRA.[6]

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 CLP.[4]

References

  1. ^ 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. PMID 10858496. 
  2. ^ a b "Entrez Gene: PDGFC platelet derived growth factor C". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56034. 
  3. ^ 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. PMID 10806482. 
  4. ^ a b 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 (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. PMID 15361870. 
  5. ^ 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. (December 2009). "The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional activity and is associated with CL/P". European Journal of Human Genetics 17 (11): 774–84. doi:10.1038/ejhg.2008.245. PMC 2788748. PMID 19092777. http://www.nature.com/ejhg/journal/v17/n6/full/ejhg2008245a.html. 
  6. ^ 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. PMID 11297552. 

Further reading


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