PDGFRB

Official Full Name

platelet derived growth factor receptor beta

Organism

Homo sapiens

Gene ID

5159

Background

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]

Synonyms

IMF1; KOGS; IBGC4; JTK12; OPDKD; PDGFR; PENTT; CD140B; PDGFR1; PDGFR-1

Bio Chemical Class

mRNA target

Protein Sequence

MRLPGAMPALALKGELLLLSLLLLLEPQISQGLVVTPPGPELVLNVSSTFVLTCSGSAPVVWERMSQEPPQEMAKAQDGTFSSVLTLTNLTGLDTGEYFCTHNDSRGLETDERKRLYIFVPDPTVGFLPNDAEELFIFLTEITEITIPCRVTDPQLVVTLHEKKGDVALPVPYDHQRGFSGIFEDRSYICKTTIGDREVDSDAYYVYRLQVSSINVSVNAVQTVVRQGENITLMCIVIGNEVVNFEWTYPRKESGRLVEPVTDFLLDMPYHIRSILHIPSAELEDSGTYTCNVTESVNDHQDEKAINITVVESGYVRLLGEVGTLQFAELHRSRTLQVVFEAYPPPTVLWFKDNRTLGDSSAGEIALSTRNVSETRYVSELTLVRVKVAEAGHYTMRAFHEDAEVQLSFQLQINVPVRVLELSESHPDSGEQTVRCRGRGMPQPNIIWSACRDLKRCPRELPPTLLGNSSEEESQLETNVTYWEEEQEFEVVSTLRLQHVDRPLSVRCTLRNAVGQDTQEVIVVPHSLPFKVVVISAILALVVLTIISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQLVLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKMLKSTARSSEKQALMSELKIMSHLGPHLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNALPVGLPLPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVPSAPERTCRATLINESPVLSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLVKICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLGGTPYPELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLERLLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGFHGLRSPLDTSSVLYTAVQPNEGDNDYIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQVEPEPELEQLPDSGCPAPRAEAEDSFL

Open

Approved Drug

3 +

Clinical Trial Drug

6 +

Discontinued Drug

5 +

Cat.No.	Product Name	Price
CLOE-1360	Human PDGFRB HEK293 Cell Lysate	Inquiry
CLOE-1361	Human PDGFRB(His) HEK293 Cell Lysate	Inquiry
CLOE-1362	Human PDGFRB(His/Fc) HEK293 Cell Lysate	Inquiry
CLOE-1949	Rat Pdgfrb (His) HEK293 Cell Lysate	Inquiry
CLOE-1955	Rat Pdgfrb (Fc) HEK293 Cell Lysate	Inquiry

Cat.No.	Product Name	Price
AD12024Z	Human PDGFRB adenoviral particles	Inquiry
LV00422Z	Mouse Pdgfrb lentiviral particles	Inquiry

Cat.No.	Product Name	Price
SHH372700	shRNA set against Mouse PDGFRB (NM_008809.2)	Inquiry
SHH372704	shRNA set against Rat PDGFRB (NM_031525.1)	Inquiry
SHW013663	shRNA set against Danio rerio PDGFRB (NM_001190933)	Inquiry

Cat.No.	Product Name	Price
RP00236	Recombinant Human PDGFRB (C-6His)	Inquiry

Cat.No.	Product Name	Price
CDCL147587	Mouse Pdgfrb ORF clone (NM_001146268.1)	Inquiry
CDCR246168	Mouse Pdgfrb ORF Clone(NM_008809.2)	Inquiry
CDFR012685	Rat Pdgfrb cDNA Clone(NM_031525.1)	Inquiry
MiUTR1R-05726	PDGFRB miRNA 3'UTR clone	Inquiry
CDCB156656	Cynomolgus PDGFRB ORF clone	Inquiry
CDCB175138	Danio rerio PDGFRB ORF Clone (NM_001190933)	Inquiry
CDCB191977	Rabbit PDGFRB ORF clone (XM_002710305.2)	Inquiry
CDCL185673	Rat PDGFRB ORF clone(NM_031525.1)	Inquiry

Detailed Information

The PDGFRB gene is located on chromosome 5q32 and consists of 25 exons. It encodes a transmembrane tyrosine kinase receptor comprising 1,106 amino acids. The protein shares high homology with PDGFRA, though it differs in ligand specificity: PDGFRB is exclusively activated by PDGF-BB or PDGF-DD, forming either homodimers or heterodimers with PDGFRA. A notable feature of this gene locus is its proximity to the colony-stimulating factor 1 (CSF1) and its receptor gene (CSF1R). These three genes are often co-deleted due to 5q deletions, contributing to the pathogenesis of the 5q-syndrome, which is characterized by myelodysplastic features and megaloblastic anemia.

PDGFRB plays a critical physiological role in vascular system development by recruiting pericytes and smooth muscle cells to endothelial cells, thereby stabilizing nascent blood vessels. Gene knockout models have shown that Pdgfrb⁻/⁻ mice suffer embryonic lethality due to vascular fragility.

Figure 1. Localization of PDGFR mutations associated with human diseases. (Guérit E, et al., 2021)

Fusion Genes and Hematologic Malignancies

Chromosomal translocations involving PDGFRB result in fusion genes that are key drivers of myeloproliferative neoplasms (MPNs). Over 30 fusion partners have been identified. These chimeric genes characteristically preserve the PDGFRB tyrosine kinase domain while substituting the N-terminal with a dimerization domain from the partner gene, leading to constitutive kinase activation. Clinical features commonly associated with these fusions include:

Eosinophilia: Observed in more than 90% of patients, attributed to fusion protein-mediated IL-5 pathway activation.
Organ infiltration: Cardiac fibrosis, pulmonary infiltration, and cutaneous involvement (20%) are frequent findings.
Risk of leukemic transformation: Up to 40% of patients may progress to acute myeloid leukemia (AML) within ten years.

Representative fusion types include:

ETV6–PDGFRB (t(5;12)): Accounts for ~50% of cases, typically presenting as chronic eosinophilic leukemia (CEL).
WDR48–PDGFRB (t(5;15)): Associated with early-onset myocardial fibrosis.
KANK1–PDGFRB (t(5;9)): Often involves meningeal infiltration.

Targeted Therapeutic Strategies

PDGFRB fusion proteins are highly sensitive to tyrosine kinase inhibitors (TKIs):

Imatinib (First-line therapy): A low dose (100 mg/day) can induce a hematologic remission rate of approximately 95% and a complete cytogenetic remission rate of 80%.
Dasatinib: Effective in cases with ETV6–PDGFRB fusion, especially when imatinib resistance occurs due to mutations such as T681I.

Mechanisms of resistance include:

Gatekeeper mutations: These hinder imatinib binding.
Fusion partner-dependent signaling: For example, WDR48–PDGFRB may activate STAT3 signaling to bypass TKI suppression.

New-generation agents such as CHZ868, a type II allosteric inhibitor, retain efficacy against gatekeeper mutation models.

Challenges in Clinical Translation

Diagnostic delay: Detection of fusion genes requires RNA sequencing, with a median diagnostic delay of approximately 14 months.
Relapse after treatment discontinuation: Despite deep remission, relapse occurs in over 70% of cases following TKI withdrawal, necessitating indefinite maintenance therapy.
Tissue-specific toxicity: TKI-induced vascular endothelial injury can result in pulmonary arterial hypertension (incidence ~15%), mandating routine cardiac function monitoring.

References:

Guérit E, Arts F, Dachy G, Boulouadnine B, et al. PDGF receptor mutations in human diseases. Cell Mol Life Sci. 2021 Apr;78(8):3867-3881.
Wang Z, Wan L, Lin D, et al. Myeloid Neoplasm with PCM1-PDGFRB Transcript Responded to Low-Dose Imatinib: One Case Report with Literature Review. Acta Haematol. 2022;145(5):560-565.

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