Platelet-derived growth factor receptor beta
Also known as: PDGFR, PDGFR1, PDGFRB
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor.
Classification
- Family (Pfam)
- PF13927 Ig_3, PF25305 Ig_PDGFR_d4, PF07714 PK_Tyr_Ser-Thr, PF22854 VEGFR1-3_N_Ig-like
- InterPro
- Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_sub, Ig_sub2, Kinase-like_dom_sf, PGFRB, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS, VEGFR1-3_N_Ig-like
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 8
- 1GQ5 X-ray 2.20A
- 1H9O X-ray 1.79A
- 1SHA X-ray 1.50A
- 2IUI X-ray 2.40A
- 2L6W NMR
- 2PLD NMR
- 2PLE NMR
- 3MJG X-ray 2.30A
A predicted model is available from AlphaFold.
Gene Ontology · 56
- GO:0016324 apical plasma membrane
- GO:0005737 cytoplasm
- GO:0031410 cytoplasmic vesicle
- GO:0005925 focal adhesion
- GO:0043202 lysosomal lumen
- GO:0016020 membrane
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0043235 receptor complex
- GO:0005524 ATP binding
- GO:0019899 enzyme binding
- GO:0005096 GTPase activator activity
- GO:0160185 phospholipase C activator activity
- GO:0004992 platelet activating factor receptor activity
- GO:0005019 platelet-derived growth factor beta-receptor activity
- GO:0048407 platelet-derived growth factor binding
- GO:0005017 platelet-derived growth factor receptor activity
- GO:0005161 platelet-derived growth factor receptor binding
- GO:0004672 protein kinase activity
- GO:0019901 protein kinase binding
- GO:0004713 protein tyrosine kinase activity
- GO:0005102 signaling receptor binding
- GO:0038085 vascular endothelial growth factor binding
- GO:0001525 angiogenesis
- GO:0035909 aorta morphogenesis
- GO:0055003 cardiac myofibril assembly
- GO:0060326 cell chemotaxis
- GO:0060981 cell migration involved in coronary angiogenesis
- GO:0035441 cell migration involved in vasculogenesis
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:0072277 metanephric glomerular capillary formation
- GO:0072262 metanephric glomerular mesangial cell proliferation involved in metanephros development
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0048008 platelet-derived growth factor receptor signaling pathway
- GO:0035791 platelet-derived growth factor receptor-beta signaling pathway
- GO:0090280 positive regulation of calcium ion import
- GO:0050850 positive regulation of calcium-mediated signaling
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:0038091 positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway
- GO:0050921 positive regulation of chemotaxis
- GO:2000573 positive regulation of DNA biosynthetic process
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0043406 positive regulation of MAP kinase activity
- GO:0035793 positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway
- GO:0045840 positive regulation of mitotic nuclear division
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:2000379 positive regulation of reactive oxygen species metabolic process
- GO:0014911 positive regulation of smooth muscle cell migration
- GO:0048661 positive regulation of smooth muscle cell proliferation
- GO:0046777 protein autophosphorylation
- GO:0032956 regulation of actin cytoskeleton organization
- GO:0061298 retina vasculature development in camera-type eye
- GO:0007165 signal transduction
- GO:0014805 smooth muscle adaptation
- GO:0071670 smooth muscle cell chemotaxis
Disease associations
- myeloproliferative disorder, chronic, with eosinophilia MONDO:0007546
- myofibromatosis, infantile, 1 MONDO:0009227
- acute myeloid leukemia MONDO:0018874
- acroosteolysis-keloid-like lesions-premature aging syndrome MONDO:0011150
- juvenile myelomonocytic leukemia MONDO:0011908
- basal ganglia calcification, idiopathic, 4 MONDO:0014004
- skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome MONDO:0014704
- ocular pterygium-digital keloid dysplasia syndrome MONDO:0976136
Drugs targeting this protein · 36
- VATALANIB inhibitor
- SORAFENIB TOSYLATE inhibitor
- PAZOPANIB HYDROCHLORIDE inhibitor
- FORETINIB inhibitor
- TANDUTINIB inhibitor
- FAMITINIB inhibitor
- DASATINIB ANHYDROUS inhibitor
- SUNITINIB MALATE inhibitor
- IMATINIB MESYLATE inhibitor
- SU-014813 inhibitor
- MASITINIB inhibitor
- REGORAFENIB inhibitor
- ILORASERTIB inhibitor
- RG-1530 inhibitor
- TELATINIB inhibitor
- CRENOLANIB inhibitor
- TIVOZANIB HYDROCHLORIDE inhibitor
- TAK-593 inhibitor
- LINIFANIB inhibitor
- ORANTINIB inhibitor
- NINTEDANIB ESYLATE inhibitor
- JI-101 inhibitor
- PD-0166285 HYDROCHLORIDE inhibitor
- TG100-801 inhibitor
- CATEQUENTINIB inhibitor
- PUQUITINIB MESYLATE DIHYDRATE inhibitor
- SERALUTINIB inhibitor
- CEDIRANIB inhibitor
- DOVITINIB inhibitor
- ENMD-981693 inhibitor
- XL-999 inhibitor
- SUNITINIB inhibitor
- MOTESANIB inhibitor
- QUIZARTINIB inhibitor
- CEP-2563 DIHYDROCHLORIDE inhibitor
- MIDOSTAURIN inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Platelet-derived growth factor receptor beta 0.99
- Platelet-derived growth factor receptor beta 0.98
- Platelet-derived growth factor receptor beta 0.98
- Macrophage colony-stimulating factor 1 receptor 0.92
- Macrophage colony-stimulating factor 1 receptor 0.92
- Macrophage colony-stimulating factor 1 receptor 0.92
- Macrophage colony-stimulating factor 1 receptor 0.92
- Mast/stem cell growth factor receptor Kit 0.91
- Platelet-derived growth factor receptor beta 0.91
- Tyrosine-protein kinase transforming protein fms 0.90
- Macrophage colony-stimulating factor 1 receptor 1 0.90
- Platelet-derived growth factor receptor alpha 0.89
Co-cited proteins · studied together in the literature
- Platelet-derived growth factor receptor alpha 10 shared papers
- Cytospin-B 1 shared papers
- Platelet-derived growth factor subunit B 3 shared papers
- Sodium-dependent phosphate transporter 2 1 shared papers
- Centrosomal protein of 85 kDa-like 1 shared papers
- Platelet-derived growth factor subunit A 2 shared papers
- Myomegalin 1 shared papers
- Thyroid receptor-interacting protein 11 1 shared papers
- Neurogenic locus notch homolog protein 3 1 shared papers
- SH2 domain-containing adapter protein B 1 shared papers
- Transcription factor ETV6 1 shared papers
- Platelet-derived growth factor receptor beta 3 shared papers
Literature · 61 cited papers
- Temperature-dependent autoactivation associated with clinical variability of PDGFRB Asn666 substitutions. Hum. Mol. Genet. · 2021
- A tyrosine kinase-activating variant Asn666Ser in PDGFRB causes a progeria-like condition in the severe end of Penttinen syndrome. Eur. J. Hum. Genet. · 2019
- Functional characterization of germline mutations in PDGFB and PDGFRB in primary familial brain calcification. PLoS ONE · 2015
- A point mutation in PDGFRB causes autosomal-dominant Penttinen syndrome. Am. J. Hum. Genet. · 2015
- Novel overgrowth syndrome phenotype due to recurrent de novo PDGFRB mutation. J. Pediatr. · 2015
- Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification. Brain · 2013
- Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am. J. Hum. Genet. · 2013
- A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am. J. Hum. Genet. · 2013
- Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification. Neurology · 2013
- Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated myeloproliferative neoplasm. Genes Chromosomes Cancer · 2012
- Glyceollins inhibit platelet-derived growth factor-mediated human arterial smooth muscle cell proliferation and migration. Br. J. Nutr. · 2012
- Disruption of platelet-derived growth factor-dependent phosphatidylinositol 3-kinase and phospholipase Cgamma 1 activity abolishes vascular smooth muscle cell proliferation and migration and attenuates neointima formation in vivo. J. Am. Coll. Cardiol. · 2011
- … and 49 more in the literature graph