The Function of PDGFRB
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 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.
Protein names
Recommended name:
Platelet-derived growth factor receptor betaShort name:
PDGFR-1Alternative name(s):
PDGF-R-betaPDGFR-beta
Beta platelet-derived growth factor receptor
Beta-type platelet-derived growth factor receptor
CD140 antigen-like family member B
Platelet-derived growth factor receptor 1
CD antigen CD140b
- RS17708574 (PDGFRB) ??
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Top Gene-Substance Interactions
PDGFRB Interacts with These Diseases
| Disease | Score |
Substances That Increase PDGFRB
| Substances | Interaction | Organism | Category |
Substances That Decrease PDGFRB
| Substances | Interaction | Organism | Category |
Advanced Summary
familial idiopathic basal ganglia calcification At least two mutations in the PDGFRB gene have been found to cause familial idiopathic basal ganglia calcification (FIBGC). This condition is characterized by abnormal deposits of calcium (calcification) in the brain, which can lead to movement and psychiatric problems. These mutations change single protein building blocks (amino acids) in the PDGFRβ protein. It is unclear how PDGFRB gene mutations cause FIBGC. Mutations may alter signaling within cells that line blood vessels in the brain, causing them to take in excess calcium, and leading to calcification of the lining of these blood vessels. Alternatively, changes in the PDGFRβ protein can alter phosphate transport signaling pathways, causing an increase in phosphate levels. In the brain, the excess phosphate combines with calcium and forms deposits. The PDGFRB gene is active (expressed) throughout the body; it is unclear why the effects of these mutations are limited to the basal ganglia and other brain regions that are involved in FIBGC. PDGFRB-associated chronic eosinophilic leukemia Genetic rearrangements (translocations) involving the PDGFRB gene cause a type of cancer of blood-forming cells called PDGFRB-associated chronic eosinophilic leukemia. This condition is characterized by an increased number of eosinophils, a type of white blood cell. The most common of these translocations brings together part of the PDGFRB gene with another gene called ETV6, whose function is to turn off gene activity. Together, these pieces create the ETV6-PDGFRB fusion gene. Occasionally, genes other than ETV6 are fused with the PDGFRB gene. The translocations that lead to these fusion genes are somatic mutations, which are acquired during a person's lifetime and occur initially in a single cell. This cell continues to grow and divide, producing a group of cells with the same mutation (a clonal population). The protein produced from the ETV6-PDGFRB fusion gene (as well as other PDGFRB fusion genes) functions differently than the proteins normally produced from the individual genes. The ETV6/PDGFRβ fusion protein does not require ligand binding to be activated and cannot bind to DNA to turn off gene activity. As a result, signaling pathways are constantly turned on (constitutively activated) and gene activity is increased, which increases the proliferation and survival of cells. When the ETV6-PDGFRB fusion gene mutation occurs in cells that develop into blood cells, the growth of eosinophils (and occasionally other white blood cells, such as neutrophils and mast cells) is poorly controlled, leading to PDGFRB-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.
The PDGFRB gene provides instructions for making a protein called platelet-derived growth factor receptor beta (PDGFRβ), which is part of a family of proteins called receptor tyrosine kinases. Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The PDGFRβ protein is found in the cell membrane of certain cell types, where a protein called platelet-derived growth factor attaches (binds) to it. This binding turns on (activates) the PDGFRβ protein, which then activates other proteins inside the cell by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. This process, called phosphorylation, leads to the activation of a series of proteins in multiple signaling pathways. The signaling pathways stimulated by the PDGFRβ protein control many important processes in the cell such as growth and division (proliferation), movement, and survival. PDGFRβ protein signaling is important for the development of many types of cells throughout the body.
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Gene Pathways:
Enzyme Regulation:
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib.
Molecular Function:
- Protein Tyrosine Kinase Activity
- Platelet Activating Factor Receptor Activity
- Platelet-Derived Growth Factor-Activated Receptor Activity
- Platelet-Derived Growth Factor Beta-Receptor Activity
- Ras Guanyl-Nucleotide Exchange Factor Activity
- Receptor Binding
- Platelet-Derived Growth Factor Receptor Binding
- Atp Binding
- Enzyme Binding
- Protein Kinase Binding
- Vascular Endothelial Growth Factor Binding
- Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Activity
- Platelet-Derived Growth Factor Binding
Biological Processes:
- Mapk Cascade
- Glycosaminoglycan Biosynthetic Process
- Signal Transduction
- Positive Regulation Of Cell Proliferation
- Response To Toxic Substance
- Positive Regulation Of Phospholipase C Activity
- Regulation Of Phosphatidylinositol 3-Kinase Signaling
- Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
- Positive Regulation Of Smooth Muscle Cell Migration
- Peptidyl-Tyrosine Phosphorylation
- Positive Regulation Of Cell Migration
- Response To Estradiol
- Positive Regulation Of Phosphoprotein Phosphatase Activity
- Response To Retinoic Acid
- Regulation Of Actin Cytoskeleton Organization
- Positive Regulation Of Collagen Biosynthetic Process
- Response To Fluid Shear Stress
- Positive Regulation Of Rho Protein Signal Transduction
- Cell Migration Involved In Vasculogenesis
- Metanephric Mesenchymal Cell Migration
- Platelet-Derived Growth Factor Receptor-Beta Signaling Pathway
- Positive Regulation Of Metanephric Mesenchymal Cell Migration By Platelet-Derived Growth Factor Receptor-Beta Signaling Pathway
- Aorta Morphogenesis
- Positive Regulation Of Cell Proliferation By Vegf-Activated Platelet Derived Growth Factor Receptor Signaling Pathway
- Wound Healing
- Response To Hydrogen Peroxide
- Positive Regulation Of Apoptotic Process
- Negative Regulation Of Apoptotic Process
- Positive Regulation Of Map Kinase Activity
- Positive Regulation Of Phosphatidylinositol 3-Kinase Activity
- Response To Estrogen
- Positive Regulation Of Mitotic Nuclear Division
- Phosphatidylinositol Metabolic Process
- Protein Autophosphorylation
- Platelet-Derived Growth Factor Receptor Signaling Pathway
- Phosphatidylinositol-Mediated Signaling
- Positive Regulation Of Fibroblast Proliferation
- Positive Regulation Of Smooth Muscle Cell Proliferation
- Inner Ear Development
- Positive Regulation Of Chemotaxis
- Cardiac Myofibril Assembly
- Response To Hyperoxia
- Cell Chemotaxis
- Cell Migration Involved In Coronary Angiogenesis
- Retina Vasculature Development In Camera-Type Eye
- Positive Regulation Of Erk1 And Erk2 Cascade
- Smooth Muscle Cell Chemotaxis
- Metanephric Mesenchyme Development
- Metanephric Glomerular Mesangial Cell Proliferation Involved In Metanephros Development
- Metanephric Glomerular Capillary Formation
- Metanephric Comma-Shaped Body Morphogenesis
- Metanephric S-Shaped Body Morphogenesis
- Positive Regulation Of Calcium Ion Import
- Positive Regulation Of Reactive Oxygen Species Metabolic Process
- Positive Regulation Of Hepatic Stellate Cell Activation
- Positive Regulation Of Dna Biosynthetic Process
Drug Bank:
- Becaplermin
- Imatinib
- Regorafenib
- Sorafenib
- Sunitinib
- Dasatinib
- Pazopanib