PDGFRA

PDGFRA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GQ5
Identifiers
Aliases	PDGFRA, CD140A, PDGFR-2, PDGFR2, RHEGAS9, platelet derived growth factor receptor alpha
External IDs	MGI: 97530 HomoloGene: 31361 GeneCards: PDGFRA
Genetically Related Diseases
astigmatism[1]
Targeted by Drug
cediranib, crenolanib, masitinib, nintedanib[2]
Gene ontology Molecular function • vascular endothelial growth factor-activated receptor activity • transferase activity • protein kinase activity • nucleotide binding • protein homodimerization activity • vascular endothelial growth factor binding • platelet-derived growth factor receptor binding • kinase activity • protein binding • platelet-derived growth factor binding • transmembrane receptor protein tyrosine kinase activity • platelet-derived growth factor alpha-receptor activity • protein tyrosine kinase activity • ATP binding • Ras guanyl-nucleotide exchange factor activity • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Cellular component • cytoplasm • integral component of membrane • membrane • intrinsic component of plasma membrane • plasma membrane • integral component of plasma membrane • protein complex • nucleus Biological process • embryonic skeletal system morphogenesis • regulation of actin cytoskeleton reorganization • luteinization • regulation of chemotaxis • phosphorylation • positive regulation of phospholipase C activity • transmembrane receptor protein tyrosine kinase signaling pathway • positive regulation of cell migration • positive regulation of fibroblast proliferation • positive regulation of cytosolic calcium ion concentration • retina vasculature development in camera-type eye • wound healing • cell activation • MAPK cascade • positive regulation of phosphatidylinositol 3-kinase activity • cellular response to reactive oxygen species • positive regulation of DNA replication • cardiac myofibril assembly • negative regulation of platelet activation • metanephric glomerular capillary formation • protein phosphorylation • chemotaxis • multicellular organism development • positive regulation of cell proliferation • positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway • positive regulation of ERK1 and ERK2 cascade • embryonic digestive tract morphogenesis • cell chemotaxis • platelet-derived growth factor receptor-alpha signaling pathway • protein autophosphorylation • positive regulation of phosphatidylinositol 3-kinase signaling • peptidyl-tyrosine phosphorylation • platelet-derived growth factor receptor signaling pathway • embryonic cranial skeleton morphogenesis • viral process • platelet aggregation • regulation of mesenchymal stem cell differentiation • phosphatidylinositol-mediated signaling • positive regulation of GTPase activity • phosphatidylinositol phosphorylation • regulation of phosphatidylinositol 3-kinase signaling Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5156	18595
Ensembl	ENSG00000134853	ENSMUSG00000029231
UniProt	P16234	P26618
RefSeq (mRNA)	NM_006206	NM_001083316 NM_011058
RefSeq (protein)	NP_006197.1	NP_001076785.1 NP_035188.2
Location (UCSC)	Chr 4: 54.23 – 54.3 Mb	Chr 5: 75.15 – 75.2 Mb
PubMed search	[3]	[4]
Wikidata

View/Edit Human

View/Edit Mouse

Platelet-derived growth factor receptor, alpha polypeptide is a protein that in humans is encoded by the PDGFRA gene.

Function

This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies in knockout mice, where homozygosity is lethal, indicate that the alpha form of the platelet-derived growth factor receptor is particularly important for kidney development since mice heterozygous for the receptor exhibit defective kidney phenotypes.^[5]

Interactions

PDGFRA has been shown to interact with:

• CRK,^[6][7]
• Caveolin 1,^[8]
• Cbl gene,^[9]
• PDGFC,^[10]
• PDGFR-β,^[11][12]
• PLCG1,^[13] and
• Sodium-hydrogen antiporter 3 regulator 1.^[14]

Monoclonal Antibody

Lilly has developed Olaratumab, (LY3012207) a human IgG1 monoclonal antibody designed to bind to human PDGFRα with high affinity and block PDGF-AA, PDGF-BB, and PDGF-CC ligands from binding to the receptor and is conducting clinical trials (2016) in patients with soft-tissue sarcoma.^[15]

See also

• Platelet-derived growth factor receptor

References

1. "Diseases that are genetically associated with PDGFRA view/edit references on wikidata".
2. "Drugs that physically interact with Platelet-derived growth factor receptor alpha view/edit references on wikidata".
3. "Human PubMed Reference:".
4. "Mouse PubMed Reference:".
5. "Entrez Gene: PDGFRA platelet-derived growth factor receptor, alpha polypeptide".
6. Yokote K, Hellman U, Ekman S, Saito Y, Rönnstrand L, Saito Y, Heldin CH, Mori S (March 1998). "Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins". Oncogene. 16 (10): 1229–39. doi:10.1038/sj.onc.1201641. PMID 9546424.
7. Matsumoto T, Yokote K, Take A, Takemoto M, Asaumi S, Hashimoto Y, Matsuda M, Saito Y, Mori S (April 2000). "Differential interaction of CrkII adaptor protein with platelet-derived growth factor alpha- and beta-receptors is determined by its internal tyrosine phosphorylation". Biochem. Biophys. Res. Commun. 270 (1): 28–33. doi:10.1006/bbrc.2000.2374. PMID 10733900.
8. Yamamoto M, Toya Y, Jensen RA, Ishikawa Y (March 1999). "Caveolin is an inhibitor of platelet-derived growth factor receptor signaling". Exp. Cell Res. 247 (2): 380–8. doi:10.1006/excr.1998.4379. PMID 10066366.
9. Bonita DP, Miyake S, Lupher ML, Langdon WY, Band H (August 1997). "Phosphotyrosine binding domain-dependent upregulation of the platelet-derived growth factor receptor alpha signaling cascade by transforming mutants of Cbl: implications for Cbl's function and oncogenicity". Mol. Cell. Biol. 17 (8): 4597–610. doi:10.1128/mcb.17.8.4597. PMC 232313. PMID 9234717.
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.
11. Rupp E, Siegbahn A, Rönnstrand L, Wernstedt C, Claesson-Welsh L, Heldin CH (October 1994). "A unique autophosphorylation site in the platelet-derived growth factor alpha receptor from a heterodimeric receptor complex". Eur. J. Biochem. 225 (1): 29–41. doi:10.1111/j.1432-1033.1994.00029.x. PMID 7523122.
12. Seifert RA, Hart CE, Phillips PE, Forstrom JW, Ross R, Murray MJ, Bowen-Pope DF (May 1989). "Two different subunits associate to create isoform-specific platelet-derived growth factor receptors". J. Biol. Chem. 264 (15): 8771–8. PMID 2542288.
13. Eriksson A, Nånberg E, Rönnstrand L, Engström U, Hellman U, Rupp E, Carpenter G, Heldin CH, Claesson-Welsh L (March 1995). "Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors". J. Biol. Chem. 270 (13): 7773–81. doi:10.1074/jbc.270.13.7773. PMID 7535778.
14. Maudsley S, Zamah AM, Rahman N, Blitzer JT, Luttrell LM, Lefkowitz RJ, Hall RA (November 2000). "Platelet-derived growth factor receptor association with Na(+)/H(+) exchanger regulatory factor potentiates receptor activity". Mol. Cell. Biol. 20 (22): 8352–63. doi:10.1128/mcb.20.22.8352-8363.2000. PMC 102142. PMID 11046132.
15. https://investor.lilly.com/releasedetail.cfm?ReleaseID=969023

Further reading

• Hart CE, Bowen-Pope DF (1990). "Platelet-derived growth factor receptor: current views of the two-subunit model". J. Invest. Dermatol. 94 (6 Suppl): 53S–57S. doi:10.1111/1523-1747.ep12875065. PMID 2161888.
• Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, Shiraga S, Bainbridge T, Morich J, Heinrich MC (2005). "PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib". J. Clin. Oncol. 23 (23): 5357–64. doi:10.1200/JCO.2005.14.068. PMID 15928335.
• Lasota J, Miettinen M (2007). "KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)". Semin Diagn Pathol. 23 (2): 91–102. doi:10.1053/j.semdp.2006.08.006. PMID 17193822.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.