InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PDGFRB

Summary

InnateDB Protein

IDBP-53328.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PDGFRB

Protein Name

platelet-derived growth factor receptor, beta polypeptide

Synonyms

CD140B; IBGC4; IMF1; JTK12; PDGFR; PDGFR-1; PDGFR1;

Species

Homo sapiens

Ensembl Protein

ENSP00000261799

InnateDB Gene

IDBG-53326 (PDGFRB)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:11297552, ECO:0000269PubMed:11331881, ECO:0000269PubMed:1314164, ECO:0000269PubMed:1396585, ECO:0000269PubMed:1653029, ECO:0000269PubMed:1709159, ECO:0000269PubMed:1846866, ECO:0000269PubMed:20494825, ECO:0000269PubMed:20529858, ECO:0000269PubMed:21098708, ECO:0000269PubMed:21679854, ECO:0000269PubMed:21733313, ECO:0000269PubMed:2554309, ECO:0000269PubMed:2835772, ECO:0000269PubMed:2850496, ECO:0000269PubMed:7685273, ECO:0000269PubMed:7691811, ECO:0000269PubMed:7692233, ECO:0000269PubMed:8195171}.

Subcellular Localization

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

Disease Associations

Note=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) [MIM:131440]: A hematologic disorder characterized by malignant eosinophils proliferation. Note=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). {ECO:0000269PubMed:12181402, ECO:0000269PubMed:12907457, ECO:0000269PubMed:15492236, ECO:0000269PubMed:21938754}.Leukemia, acute myelogenous (AML) [MIM:601626]: 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. Note=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). {ECO:0000269PubMed:9373237}.Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: 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. Note=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). {ECO:0000269PubMed:15087372}.Basal ganglia calcification, idiopathic, 4 (IBGC4) [MIM:615007]: 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. {ECO:0000269PubMed:23255827}. Note=The disease is caused by mutations affecting the gene represented in this entry.Myofibromatosis, infantile 1 (IMF1) [MIM:228550]: 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. {ECO:0000269PubMed:23731537, ECO:0000269PubMed:23731542}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 124 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	124 [view]
Protein-Protein	124 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0004871	signal transducer activity
GO:0004992	platelet activating factor receptor activity
GO:0005017	platelet-derived growth factor-activated receptor activity
GO:0005019	platelet-derived growth factor beta-receptor activity
GO:0005102	receptor binding
GO:0005161	platelet-derived growth factor receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0038085	vascular endothelial growth factor binding
GO:0043548	phosphatidylinositol 3-kinase binding
GO:0048407	platelet-derived growth factor binding

Biological Process

GO:0001701	in utero embryonic development
GO:0001822	kidney development
GO:0001894	tissue homeostasis
GO:0006024	glycosaminoglycan biosynthetic process
GO:0006468	protein phosphorylation
GO:0006807	nitrogen compound metabolic process
GO:0007165	signal transduction
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007186	G-protein coupled receptor signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009636	response to toxic substance
GO:0010863	positive regulation of phospholipase C activity
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0014070	response to organic cyclic compound
GO:0014911	positive regulation of smooth muscle cell migration
GO:0016477	cell migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030325	adrenal gland development
GO:0030335	positive regulation of cell migration
GO:0032355	response to estradiol
GO:0032516	positive regulation of phosphoprotein phosphatase activity
GO:0032526	response to retinoic acid
GO:0032956	regulation of actin cytoskeleton organization
GO:0032967	positive regulation of collagen biosynthetic process
GO:0033993	response to lipid
GO:0034405	response to fluid shear stress
GO:0035441	cell migration involved in vasculogenesis
GO:0035556	intracellular signal transduction
GO:0035789	metanephric mesenchymal cell migration
GO:0035791	platelet-derived growth factor receptor-beta signaling pathway
GO:0035793	positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway
GO:0035909	aorta morphogenesis
GO:0036120	cellular response to platelet-derived growth factor stimulus
GO:0038091	positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042060	wound healing
GO:0042542	response to hydrogen peroxide
GO:0043066	negative regulation of apoptotic process
GO:0043406	positive regulation of MAP kinase activity
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0043627	response to estrogen
GO:0045087	innate immune response
GO:0045840	positive regulation of mitosis
GO:0046488	phosphatidylinositol metabolic process
GO:0046777	protein autophosphorylation
GO:0048008	platelet-derived growth factor receptor signaling pathway
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0048661	positive regulation of smooth muscle cell proliferation
GO:0048705	skeletal system morphogenesis
GO:0048745	smooth muscle tissue development
GO:0048839	inner ear development
GO:0050730	regulation of peptidyl-tyrosine phosphorylation
GO:0050921	positive regulation of chemotaxis
GO:0055003	cardiac myofibril assembly
GO:0055093	response to hyperoxia
GO:0060326	cell chemotaxis
GO:0060981	cell migration involved in coronary angiogenesis
GO:0061298	retina vasculature development in camera-type eye
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0071670	smooth muscle cell chemotaxis
GO:0072075	metanephric mesenchyme development
GO:0072262	metanephric glomerular mesangial cell proliferation involved in metanephros development
GO:0072275	metanephric glomerulus morphogenesis
GO:0072277	metanephric glomerular capillary formation
GO:0072278	metanephric comma-shaped body morphogenesis
GO:0072284	metanephric S-shaped body morphogenesis
GO:0090280	positive regulation of calcium ion import
GO:2000379	positive regulation of reactive oxygen species metabolic process
GO:2000573	positive regulation of DNA biosynthetic process

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0016324	apical plasma membrane
GO:0031226	intrinsic component of plasma membrane
GO:0043202	lysosomal lumen
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR013151 Immunoglobulin
IPR016243 Tyrosine-protein kinase, CSF-1/PDGF receptor
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF07679
PF00047

PRINTS

PR00109

PIRSF

PIRSF000615
PIRSF500947

SMART

SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References