PDGFRB

The protein encoded by this gene is 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 (PDGFB or PDGFD) or a heterodimer (PDGFA and PDGFB). This gene is essential for normal development of the cardiovascular system and aids in rearrangement of the actin cytoskeleton. This gene is flanked on chromosome 5 by the genes for granulocyte-macrophage colony-stimulating factor and macrophage-colony stimulating factor receptor; all three genes may be implicated in the 5-q syndrome. A translocation between chromosomes 5 and 12, that fuses this gene to that of the ETV6 gene, results in chronic myeloproliferative disorder with eosinophilia. [provided by RefSeq, Aug 2017]

Platelet Derived Growth Factor Receptor Beta

Tyrosine-protein kinase that acts as 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 Ca2+ 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.

AgingIEA:Ensembl
AngiogenesisManual Assertion Based On ExperimentIBA:GO_Central
Aorta morphogenesisISS:BHF-UCL
Cardiac myofibril assemblyISS:UniProtKB
Cell chemotaxisManual Assertion Based On ExperimentIDA:UniProtKB
Cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Cell migration involved in coronary angiogenesisISS:UniProtKB
Cell migration involved in vasculogenesisISS:UniProtKB
Glycosaminoglycan biosynthetic processIEA:Ensembl
Inner ear developmentIEA:Ensembl
Lung growthIEA:Ensembl
Male gonad developmentIEA:Ensembl
Metanephric comma-shaped body morphogenesisIEA:Ensembl
Metanephric glomerular capillary formationISS:UniProtKB
Metanephric glomerular mesangial cell proliferation involved in metanephros developmentISS:UniProtKB
Metanephric mesenchymal cell migrationIEA:Ensembl
Metanephric mesenchyme developmentIEA:Ensembl
Metanephric S-shaped body morphogenesisIEA:Ensembl
Negative regulation of apoptotic processIEA:Ensembl
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Phosphatidylinositol metabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Phosphatidylinositol-mediated signalingManual Assertion Based On ExperimentIMP:UniProtKB
Platelet-derived growth factor receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Platelet-derived growth factor receptor-beta signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of apoptotic processIEA:Ensembl
Positive regulation of calcium ion importISS:UniProtKB
Positive regulation of cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of chemotaxisISS:UniProtKB
Positive regulation of collagen biosynthetic processIEA:Ensembl
Positive regulation of DNA biosynthetic processISS:UniProtKB
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of fibroblast proliferationIEA:Ensembl
Positive regulation of hepatic stellate cell activationIEA:Ensembl
Positive regulation of kinase activityManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of MAP kinase activityISS:UniProtKB
Positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathwayISS:UniProtKB
Positive regulation of mitotic nuclear divisionISS:UniProtKB
Positive regulation of phosphatidylinositol 3-kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingISS:UniProtKB
Positive regulation of phospholipase C activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of phosphoprotein phosphatase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of reactive oxygen species metabolic processISS:UniProtKB
Positive regulation of Rho protein signal transductionIEA:Ensembl
Positive regulation of smooth muscle cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of smooth muscle cell proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of actin cytoskeleton organizationISS:BHF-UCL
Response to estradiolIEA:Ensembl
Response to estrogenIEA:Ensembl
Response to fluid shear stressIEA:Ensembl
Response to hydrogen peroxideIEA:Ensembl
Response to hyperoxiaIEA:Ensembl
Response to retinoic acidIEA:Ensembl
Response to toxic substanceIEA:Ensembl
Retina vasculature development in camera-type eyeISS:UniProtKB
Signal transductionManual Assertion Based On ExperimentIDA:UniProtKB
Smooth muscle cell chemotaxisISS:BHF-UCL
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Wound healingIEA:Ensembl

Cell membrane
Cytoplasmic vesicle
Lysosome lumen
After ligand binding, the autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation.

Myeloproliferative disorder chronic with eosinophilia (MPE):
A hematologic disorder characterized by malignant eosinophils proliferation.
Leukemia, acute myelogenous (AML):
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
Leukemia, juvenile myelomonocytic (JMML):
An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
Basal ganglia calcification, idiopathic, 4 (IBGC4):
A form of basal ganglia calcification, an autosomal dominant condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas.
Myofibromatosis, infantile 1 (IMF1):
A rare mesenchymal disorder characterized by the development of benign tumors in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about half of the patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life. Visceral lesions are associated with high morbidity and mortality.
Kosaki overgrowth syndrome (KOGS):
A syndrome characterized by somatic overgrowth, distinctive facial features, hyperelastic and fragile skin, and progressive neurologic deterioration with white matter lesions on brain imaging.
Premature aging syndrome, Penttinen type (PENTT):
A syndrome characterized by a prematurely aged appearance with lipoatrophy, epidermal and dermal atrophy along with hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acro-osteolysis.

Extracellular: 33-532
Helical: 533-553
Cytoplasmic: 554-1106

Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-579, and to a lesser degree, at Tyr-581, is important for interaction with SRC family kinases. Phosphorylation at Tyr-740 and Tyr-751 is important for interaction with PIK3R1. Phosphorylation at Tyr-751 is important for interaction with NCK1. Phosphorylation at Tyr-771 and Tyr-857 is important for interaction with RASA1/GAP. Phosphorylation at Tyr-857 is important for efficient phosphorylation of PLCG1 and PTPN11, resulting in increased phosphorylation of AKT1, MAPK1/ERK2 and/or MAPK3/ERK1, PDCD6IP/ALIX and STAM, and in increased cell proliferation. Phosphorylation at Tyr-1009 is important for interaction with PTPN11. Phosphorylation at Tyr-1009 and Tyr-1021 is important for interaction with PLCG1. Phosphorylation at Tyr-1021 is important for interaction with CBL; PLCG1 and CBL compete for the same binding site. Dephosphorylated by PTPRJ at Tyr-751, Tyr-857, Tyr-1009 and Tyr-1021. Dephosphorylated by PTPN2 at Tyr-579 and Tyr-1021.
N-glycosylated.
Ubiquitinated. After autophosphorylation, the receptor is polyubiquitinated, leading to its degradation.