PDGFC

Last updated
PDGFC
Identifiers
Aliases PDGFC , FALLOTEIN, SCDGF, platelet derived growth factor C
External IDs OMIM: 608452 MGI: 1859631 HomoloGene: 9423 GeneCards: PDGFC
Orthologs
SpeciesHumanMouse
Entrez

56034

54635

Ensembl

ENSG00000145431

ENSMUSG00000028019

UniProt

Q9NRA1

Q8CI19

RefSeq (mRNA)

NM_016205

NM_019971
NM_001357746

RefSeq (protein)

NP_057289

NP_064355
NP_001344675

Location (UCSC) Chr 4: 156.76 – 156.97 Mb Chr 3: 80.94 – 81.12 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [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]

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. [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]

Interactions

PDGFC has been shown to interact with PDGFRA. [10]

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]

Related Research Articles

<span class="mw-page-title-main">Platelet-derived growth factor</span> Signaling glycoprotein regulating cell proliferation

Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood vessel tissue, mitogenesis, i.e. proliferation, of mesenchymal cells such as fibroblasts, osteoblasts, tenocytes, vascular smooth muscle cells and mesenchymal stem cells as well as chemotaxis, the directed migration, of mesenchymal cells. Platelet-derived growth factor is a dimeric glycoprotein that can be composed of two A subunits (PDGF-AA), two B subunits (PDGF-BB), or one of each (PDGF-AB).

<span class="mw-page-title-main">Platelet-derived growth factor receptor</span> Protein family

Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. There are two forms of the PDGF-R, alpha and beta each encoded by a different gene. Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes.

<span class="mw-page-title-main">CXCL5</span> Mammalian protein found in Homo sapiens

C-X-C motif chemokine 5 is a protein that in humans is encoded by the CXCL5 gene.

<span class="mw-page-title-main">CXCL7</span> Mammalian protein found in Homo sapiens

Chemokine ligand 7 (CXCL7) is a human gene.

<span class="mw-page-title-main">Platelet-activating factor receptor</span> Protein-coding gene in the species Homo sapiens

The platelet-activating factor receptor(PAF-R) is a G-protein coupled receptor which binds platelet-activating factor. It is encoded in the human by the PTAFR gene.

<span class="mw-page-title-main">PDGFRB</span> Protein-coding gene in the species Homo sapiens

Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the PDGFRB gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.

<span class="mw-page-title-main">PDGFA</span> Mammalian protein found in Homo sapiens

Platelet-derived growth factor subunit A is a protein that in humans is encoded by the PDGFA gene.

<span class="mw-page-title-main">F2RL2</span> Protein-coding gene in the species Homo sapiens

Protease activated receptor 3 (PAR-3) also known as coagulation factor II receptor-like 2 (F2RL2) and thrombin receptor-like 2, is a protein that in humans is encoded by the F2RL2 gene.

<span class="mw-page-title-main">PDGFB</span> Protein-coding gene in the species Homo sapiens

Platelet-derived growth factor subunit B is a protein that in humans is encoded by the PDGFB gene.

<span class="mw-page-title-main">TYMP (gene)</span> Protein-coding gene in the species Homo sapiens

TYMP is a gene that encodes for the enzyme thymidine phosphorylase. The TYMP gene is also known as ECGF1 and MNGIE due to its role in MNGIE syndrome.

<span class="mw-page-title-main">F2RL3</span> Protein-coding gene in the species Homo sapiens

Protease-activated receptor 4 (PAR-4), also known as coagulation factor II (thrombin) receptor-like 3, is a protein that in humans is encoded by the F2RL3 gene.

<span class="mw-page-title-main">YES1</span> Protein-coding gene in the species Homo sapiens

Proto-oncogene tyrosine-protein kinase Yes is a non-receptor tyrosine kinase that in humans is encoded by the YES1 gene.

<span class="mw-page-title-main">Interleukin 1 receptor, type I</span>

Interleukin 1 receptor, type I (IL1R1) also known as CD121a, is an interleukin receptor. IL1R1 also denotes its human gene.

<span class="mw-page-title-main">VAV2</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide exchange factor VAV2 is a protein that in humans is encoded by the VAV2 gene.

<span class="mw-page-title-main">Collagen, type XI, alpha 1</span> Protein found in humans

Collagen alpha-1(XI) chain is a protein that in humans is encoded by the COL11A1 gene.

<span class="mw-page-title-main">PDGFD</span> Protein-coding gene in the species Homo sapiens

Platelet-derived growth factor D is a protein that in humans is encoded by the PDGFD gene.

<span class="mw-page-title-main">VAV3</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the VAV3 gene.

<span class="mw-page-title-main">PDAP1</span> Protein-coding gene in the species Homo sapiens

28 kDa heat- and acid-stable phosphoprotein is a protein that in humans is encoded by the PDAP1 gene.

<span class="mw-page-title-main">Platelet-derived growth factor receptor A</span>

Platelet-derived growth factor receptor A, also termed CD140a, is a receptor located on the surface of a wide range of cell types. The protein is encoded in the human by the PDGFRA gene. This receptor binds to certain isoforms of platelet-derived growth factors (PDGFs) and thereby becomes active in stimulating cell signaling pathways that elicit responses such as cellular growth and differentiation. The receptor is critical for the embryonic development of certain tissues and organs, and for their maintenance, particularly hematologic tissues, throughout life. Mutations in PDGFRA, are associated with an array of clinically significant neoplasms, notably ones of the clonal hypereosinophilia class of malignancies, as well as gastrointestinal stromal tumors (GISTs).

<span class="mw-page-title-main">Crenolanib</span> Chemical compound

Crenolanib besylate is an investigational inhibitor being developed by AROG Pharmaceuticals, LLC. The compound is currently being evaluated for safety and efficacy in clinical trials for various types of cancer, including acute myeloid leukemia (AML), gastrointestinal stromal tumor (GIST), and glioma. Crenolanib is an orally bioavailable benzimidazole that selectively and potently inhibits signaling of wild-type and mutant isoforms of class III receptor tyrosine kinases (RTK) FLT3, PDGFR α, and PDGFR β. Unlike most RTK inhibitors, crenolanib is a type I mutant-specific inhibitor that preferentially binds to phosphorylated active kinases with the ‘DFG in’ conformation motif.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000145431 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028019 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ 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. S2CID   19634520.
  6. 1 2 "Entrez Gene: PDGFC platelet derived growth factor C".
  7. ↑ 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. S2CID   25066476.
  8. 1 2 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.
  9. ↑ 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.
  10. ↑ 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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