PDGFRB

The protein expressed by the PDGFRB gene is a tyrosine-protein kinase that functions as a cell-surface receptor for various PDGF homodimers and heterodimers, playing an essential role in embryonic development, cell proliferation, survival, differentiation, chemotaxis, and migration. It is crucial for blood vessel development by promoting the proliferation and migration of, as well as recruitment of, pericytes and smooth muscle cells to endothelial cells. It has a role in vascular smooth muscle cell migration and neointima formation at injury sites, and is necessary for normal cardiovascular development and pericyte recruitment in kidney glomeruli. The protein facilitates actin cytoskeleton rearrangement and membrane ruffle formation. Ligand binding activates signaling cascades depending on the ligand bound and interactions with PDGFRA, leading to phosphorylation of several substrates, activation of signaling pathways such as AKT1, MAPK, and SRC family kinases, and production of molecules like diacylglycerol and inositol trisphosphate. Receptor signaling is downregulated by protein phosphatases and receptor internalization. This supplementary information is collated from multiple sources and compiled automatically.

A chromosomal aberration involving PDGFRB is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with EVT6/TEL. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML).

Myeloproliferative disorder chronic with eosinophilia

MPE

A hematologic disorder characterized by malignant eosinophils proliferation.

None

The gene represented in this entry may be involved in disease pathogenesis. Chromosomal aberrations involving PDGFRB have been found in many instances of chronic myeloproliferative disorder with eosinophilia. Translocation t(5;12) with ETV6 on chromosome 12 creating an PDGFRB-ETV6 fusion protein (PubMed:12181402). Translocation t(5;15)(q33;q22) with TP53BP1 creating a PDGFRB-TP53BP1 fusion protein (PubMed:15492236). Translocation t(1;5)(q23;q33) that forms a PDE4DIP-PDGFRB fusion protein (PubMed:12907457). Translocation t(5;6)(q33-34;q23) with CEP85L that fuses the 5'-end of CEP85L (isoform 4) to the 3'-end of PDGFRB (PubMed:21938754).

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.

None

The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving PDGFRB has been found in a patient with AML. Translocation t(5;14)(q33;q32) with TRIP11 (PubMed:9373237).

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.

None

The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving PDGFRB has been found in a patient with JMML. Translocation t(5;17)(q33;p11.2) with SPECC1 (PubMed:15087372).

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

• Cell membrane
• Single-pass type I membrane protein
• Cytoplasmic vesicle
• Lysosome lumen
• After ligand binding, the autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation.

CD140b, PDGFR, PDGFR1, PDGFRB, Platelet-derived growth factor receptor beta, PDGF-R-beta, PDGFR-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, PDGFR-1

• entrezGene:5159
• omim:173410
• swissprot:P09619

Proteins

Immunology & Infectious Disease

123968Da