platelet-derived growth factor receptor, beta polypeptide

Nomenclature: platelet-derived growth factor receptor, beta polypeptide

Abbreviated Name: PDGFRβ

Family: Receptor tyrosine kinases

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1106 5q33.1 PDGFRB platelet-derived growth factor receptor, beta polypeptide
Mouse 1 1099 18 Pdgfrb platelet derived growth factor receptor, beta polypeptide
Rat 1 1097 18q12.1 Pdgfrb platelet derived growth factor receptor, beta polypeptide
Previous and Unofficial Names
Platelet-derived growth factor receptor β
CD140b
PDGFR1
JTK12
PDGFR
PDGFRB
PDGFR-1
CD140 antigen-like family member B
PDGF-R-beta
PDGFR-beta
Platelet-derived growth factor receptor beta
Platelet-derived growth factor receptor, beta
beta platelet-derived growth factor receptor
beta-type platelet-derived growth factor receptor
platelet-derived growth factor receptor 1
platelet-derived growth factor receptor beta variant 1
Database Links
BRENDA
Ensembl Gene
Entrez Gene
ExplorEnz
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG BRITE Hierarchy
KEGG Gene
OMIM
Orphanet Gene
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  The structure of a platelet derived growth factor receptor complex
PDB Id:  3MJG
Resolution:  2.3Å
Species:  Human
References:  11
Enzyme Reaction
EC Number: 2.7.10.1
Endogenous ligands (Human)
PDGF
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
cediranib Hs Inhibition 8.3 pIC50 12
pIC50 8.3 (IC50 5x10-9 M) [12]
dovitinib Hs Inhibition 8.3 pIC50 10
pIC50 8.3 (IC50 5x10-9 M) [10]
sunitinib Hs Inhibition 8.2 pIC50 8
pIC50 8.2 (IC50 5.7x10-9 M) [8]
nintedanib Hs Inhibition 7.19 pIC50 7
pIC50 7.19 (IC50 6.5x10-8 M) [7]
linifanib Hs Inhibition 7.18 pIC50 1
pIC50 7.18 (IC50 6.6x10-8 M) [1]
vatalanib Hs Inhibition 6.22 pIC50 3
pIC50 6.22 (IC50 6x10-7 M) [3]
masitinib Hs Inhibition 6.1 pIC50 5
pIC50 6.1 (IC50 8x10-7 M) [5]
Inhibitor Comments
Note that sunitinib inhibits a range of additional kinases, including platelet-derived growth factor receptor α (PDGFRα), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3) and colony stimulating factor receptor Type 1 (CSF-1R).
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 4,13

Key to terms and symbols Click column headers to sort
Target used in screen: PDGFRB
Ligand Sp. Type Action Affinity Units
sunitinib Hs Inhibitor Inhibition 10.12 pKd
SU-14813 Hs Inhibitor Inhibition 9.54 pKd
Ki-20227 Hs Inhibitor Inhibition 9.54 pKd
cediranib Hs Inhibitor Inhibition 9.49 pKd
axitinib Hs Inhibitor Inhibition 9.24 pKd
dasatinib Hs Inhibitor Inhibition 9.2 pKd
foretinib Hs Inhibitor Inhibition 9.02 pKd
PD-173955 Hs Inhibitor Inhibition 8.85 pKd
staurosporine Hs Inhibitor Inhibition 8.74 pKd
linifanib Hs Inhibitor Inhibition 8.72 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 2,6

Key to terms and symbols Click column headers to sort
Target used in screen: PDGFRβ/PDGFRb
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 2.3 3.0 1.0
dasatinib Hs Inhibitor Inhibition 2.5
SU11652 Hs Inhibitor Inhibition 9.3 1.0 1.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 11.4 120.0 111.0
sorafenib Hs Inhibitor Inhibition 12.0
K-252a Hs Inhibitor Inhibition 14.6 46.0 8.0
midostaurin Hs Inhibitor Inhibition 14.8 46.0 25.0
dovitinib Hs Inhibitor Inhibition 17.2
masitinib Hs Inhibitor Inhibition 17.3
sunitinib Hs Inhibitor Inhibition 17.6
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Bilateral striopallidodentate calcinosis
Orphanet:  1980
References:  9
Mutations not determined
Disease:  Chronic myelomonocytic leukemia
Orphanet:  98823
References: 
Mutations not determined
Disease:  Idiopathic hypereosinophilic syndrome
Orphanet:  3260
References: 
Mutations not determined
Disease:  Myeloid neoplasm associated with PDGFRB rearrangement
Orphanet:  168950
References: 
Mutations not determined
Disease:  Unclassified chronic myeloproliferative disease
Orphanet:  86830
References: 
Mutations not determined
Disease:  Myofibromatosis, infantile, 1
OMIM:  228550
Orphanet:  2591
References: 
Mutations not determined
Disease:  Basal ganglia calcification, idiopathic, 4
OMIM:  615007
References: 
Mutations not determined
Disease:  Myeloproliferative disorder with eosinophilia
OMIM:  131440
References: 
Mutations not determined

References

Show »

1. Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, Li J, Guo J, Bousquet PF, Ghoreishi-Haack NS et al.. (2006) Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol. Cancer Ther.5 (4): 995-1006. [PMID:16648571]

2. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol.29 (11): 1039-45. [PMID:22037377]

3. Bold G, Altmann KH, Frei J, Lang M, Manley PW, Traxler P, Wietfeld B, Brüggen J, Buchdunger E, Cozens R et al.. (2000) New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. J. Med. Chem.43 (12): 2310-23. [PMID:10882357]

4. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol.29 (11): 1046-51. [PMID:22037378]

5. Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Castéran N, Borge L, Hajem B, Lermet A, Sippl W et al.. (2009) Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS ONE4 (9): e7258. [PMID:19789626]

6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J.451 (2): 313-28. [PMID:23398362]

7. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J et al.. (2008) BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res.68 (12): 4774-82. [PMID:18559524]

8. Kitagawa D, Yokota K, Gouda M, Narumi Y, Ohmoto H, Nishiwaki E, Akita K, Kirii Y. (2013) Activity-based kinase profiling of approved tyrosine kinase inhibitors. Genes Cells18 (2): 110-22. [PMID:23279183]

9. Nicolas G, Pottier C, Charbonnier C, Guyant-Maréchal L, Le Ber I, Pariente J, Labauge P, Ayrignac X, Defebvre L, Maltête D et al.. (2013) Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification. Brain136 (Pt 11): 3395-407. [PMID:24065723]

10. Renhowe PA, Pecchi S, Shafer CM, Machajewski TD, Jazan EM, Taylor C, Antonios-McCrea W, McBride CM, Frazier K, Wiesmann M et al.. (2009) Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors. J. Med. Chem.52 (2): 278-92. [PMID:19113866]

11. Shim AH, Liu H, Focia PJ, Chen X, Lin PC, He X. (2010) Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex. Proc. Natl. Acad. Sci. U.S.A.107 (25): 11307-12. [PMID:20534510]

12. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO et al.. (2005) AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res.65 (10): 4389-400. [PMID:15899831]

13. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol.17 (11): 1241-9. [PMID:21095574]

How to cite this page

Receptor tyrosine kinases: platelet-derived growth factor receptor, beta polypeptide. Last modified on 13/05/2014. Accessed on 30/10/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1804.