Affinage

PDGFRA

Platelet-derived growth factor receptor alpha · UniProt P16234

Length
1089 aa
Mass
122.7 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDGFRA is a type III receptor tyrosine kinase that transduces extracellular cues into proliferative, migratory, and differentiation programs during development and is a principal oncogenic driver when its kinase activity becomes deregulated (PMID:12522257, PMID:23970477, PMID:1846043). In its resting state the kinase is auto-inhibited by insertion of the juxtamembrane domain into the active site, which stabilizes a 'DFG-out' inactive conformation maintained by Asp842 contacts with the activation loop; the activation-loop mutation D842V disrupts this stabilization, constitutively activates the kinase, and raises ATP affinity, explaining both ligand-independent signaling and imatinib resistance (PMID:27349873). Constitutive activation arises through multiple routes: activation-loop and juxtamembrane point mutations (D842V, V561D) (PMID:15928335, PMID:27349873), extracellular-domain mutations such as Y288C that cause ER retention with ligand-independent dimerization (PMID:30389923), intragenic deletions and gene fusions (KDR-PDGFRA, FIP1L1-PDGFRA) (PMID:20889717, PMID:17440089), and ligand or paracrine inputs including PDGF-A and the endothelial proteoglycan Endocan, which binds and activates the receptor to drive Myc-dependent chromatin remodeling (PMID:11544480, PMID:39773984). Activated PDGFRA engages a converging signaling network — PI3K/AKT/mTOR (with SHP-2/PTPN11 acting upstream of PI3K), RAS/MEK/ERK, and STAT/NF-κB cascades — that mediates proliferation, migration, and lineage output (PMID:17440089, PMID:21393858, PMID:22271894, PMID:11544480). ERK activity in turn feeds back on receptor surface levels by directing PDGFRA between endosomal recycling and Golgi retention (PMID:24489888). These mutations are the dominant oncogenic mechanism in KIT-wild-type GIST, inflammatory fibroid polyps, pediatric and H3.3 G34R/V high-grade glioma, and FIP1L1-PDGFRA eosinophilic leukemia, motivating conformation-selective inhibitors such as avapritinib that engage the active state to overcome D842V resistance (PMID:12522257, PMID:29093181, PMID:17440089, PMID:23970477, PMID:18686281, PMID:33259802). Developmentally, Pdgfra is required for cardiac fibroblast and endocardial/myocardial assembly, neural crest palatogenesis, chondrocyte progenitor specification via Wnt9a suppression, and marks bipotential oligodendrocyte progenitors (PMID:24000064, PMID:26971580, PMID:32800757, PMID:1846043, PMID:28167492, PMID:21947029).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1991 High

    Established that PDGFRA loss-of-function underlies a defined developmental phenotype, demonstrating the gene's essential in vivo role before its oncogenic functions were defined.

    Evidence Genetic mapping and Southern/RNA analysis of the mouse patch (Ph) deletion encompassing Pdgfra

    PMID:1846043

    Open questions at the time
    • Does not define the cell types or signaling outputs requiring Pdgfra
    • No molecular mechanism of receptor activity addressed
  2. 2003 High

    Identified PDGFRA as an alternative oncogenic driver in KIT-wild-type GIST, establishing intragenic activating mutations as a clinically central mechanism mutually exclusive with KIT.

    Evidence Mutational sequencing of GIST tumors with downstream signaling characterization

    PMID:12522257

    Open questions at the time
    • Did not resolve the structural basis of activation
    • Did not establish inhibitor sensitivity profiles per mutation
  3. 2005 High

    Resolved which PDGFRA mutations are imatinib-sensitive versus resistant, directly informing therapy by mapping drug response to mutation site.

    Evidence Expression of PDGFRA mutant isoforms in CHO and BA/F3 cells with proliferation/inhibition assays

    PMID:15928335

    Open questions at the time
    • Mechanism of D842 resistance not yet structurally explained
    • No inhibitor effective against resistant activation-loop mutants
  4. 2007 High

    Defined the signaling output and domain requirements of the FIP1L1-PDGFRA fusion in human progenitors, linking the fusion to myeloproliferation through PI3K/ERK/STAT5.

    Evidence Retroviral transduction of CD34+ progenitors with deletion mutants, dominant-negative STAT5, and pharmacological inhibitors

    PMID:17440089

    Open questions at the time
    • Did not define how fusion alters receptor conformation/dimerization
    • Relative contribution of each pathway to leukemogenesis unresolved
  5. 2010 High

    Showed that genomic rearrangements (intragenic deletion, KDR-PDGFRA fusion) constitutively activate PDGFRA in glioma, expanding the repertoire of activation mechanisms beyond point mutation.

    Evidence Genomic analysis of glioma PDGFRA locus with kinase activity, transformation, and inhibitor-reversal assays

    PMID:20889717

    Open questions at the time
    • Structural consequence of rearrangements on the kinase not defined
    • Did not map downstream effector requirements
  6. 2011 High

    Placed SHP-2 upstream of PI3K/AKT/mTOR in PDGFRA-driven gliomagenesis, identifying a required adaptor node and a tractable epistatic relationship.

    Evidence Signaling-module PDGFRA mutants, SHP-2 knockdown/inhibition, activated-PI3K rescue, and intracranial glioma model

    PMID:21393858

    Open questions at the time
    • Direct biochemistry of the PDGFRA–SHP-2 interface not crystallographically resolved
    • Generality across tumor types not established
  7. 2011 Medium

    Established CD140a/PDGFRα as a marker of bipotential human oligodendrocyte progenitors with superior myelination capacity, linking receptor expression to a defined neural lineage.

    Evidence FACS isolation, in vitro differentiation, and xenotransplantation into shiverer mice

    PMID:21947029

    Open questions at the time
    • Did not test whether PDGFRA signaling is required for OPC fate versus merely marking it
    • Single lab
  8. 2012 High

    Extended fusion-oncogene signaling to STAT1/3/5 and NF-κB, showing PI3K-dependent NF-κB drives the eosinophil differentiation program characteristic of these leukemias.

    Evidence CD34+ transduction with dominant-negative IκB, PI3K inhibition, and gene expression microarrays

    PMID:22271894

    Open questions at the time
    • Direct NF-κB target genes for lineage skewing only partially mapped
    • Did not distinguish PDGFRA-specific versus PDGFRB-shared effects
  9. 2013 High

    Showed that novel pediatric high-grade glioma PDGFRA mutations are bona fide ligand-independent oncogenic drivers in vivo, broadening the disease spectrum.

    Evidence Full-coding sequencing, receptor phosphorylation assays, and p53-null astrocyte transformation with intracranial implantation

    PMID:23970477

    Open questions at the time
    • Inhibitor sensitivity of each mutant not exhaustively mapped
    • Co-occurring genetic context dependence not addressed here
  10. 2016 High

    Provided the structural basis of PDGFRA auto-inhibition and D842V activation, mechanistically explaining constitutive activity and imatinib resistance.

    Evidence X-ray crystallography of the kinase domain plus ATP-affinity kinetics for D842V

    PMID:27349873

    Open questions at the time
    • Full-length receptor and ligand-bound conformations not captured
    • Structure did not directly model inhibitor engagement
  11. 2017 High

    Delivered a conformation-selective inhibitor (avapritinib) engaging the active state to overcome D842V resistance, translating structural insight into a therapy for resistant mutants.

    Evidence In vitro kinase assays, preclinical models, and phase 1 clinical evaluation

    PMID:29093181

    Open questions at the time
    • Mechanisms of secondary resistance not yet defined
    • Precise binding-pocket interactions not crystallographically resolved at this stage
  12. 2017 Medium

    Identified cross-talk and dependency relationships of PDGFRA with EGFR and Src family kinases, revealing combinatorial requirements for tumor maintenance.

    Evidence Co-IP/heterodimerization and transactivation in GBM spheres; Src/Pdgfra epistasis in aRMS with KO and inhibitor combinations in vitro and in vivo

    PMID:22960170 PMID:28831081 PMID:33707748

    Open questions at the time
    • Stoichiometry and direct versus indirect nature of EGFR-PDGFRA association not fully defined
    • Co-IP-based heterodimerization without reciprocal structural validation
  13. 2018 High

    Revealed an extracellular-domain activation mechanism (Y288C) driven by altered glycosylation and ER-associated ligand-independent dimerization, with a distinct inhibitor-sensitivity profile.

    Evidence Glycosylation, dimerization, and phosphorylation assays with inhibitor sensitivity profiling in cell lines

    PMID:30389923

    Open questions at the time
    • Subcellular site of active signaling not directly imaged
    • Frequency across tumor types not established
  14. 2020 Medium

    Defined avapritinib secondary-resistance mutations and confirmed continued PDGFRA dependence, establishing the receptor as a persistent therapeutic target at progression.

    Evidence Tumor and plasma sequencing of progressing patients with functional analysis of resistance mutations

    PMID:32972961

    Open questions at the time
    • Binding interference inferred structurally, not demonstrated biochemically
    • Did not test next-generation inhibitors against these mutants
  15. 2020 Medium

    Connected PDGFRA to chromatin-level regulation and trafficking in disease: a chromatin loop driving PDGFRA overexpression in G34R/V glioma, and endosomal PDGFRA driving TGFB1/SMAD fibrosis in CKD.

    Evidence Chromatin conformation and oncogenicity assays in glioma; conditional Pdgfra KO with endosomal localization and SMAD signaling in an AVF/CKD model

    PMID:33001865 PMID:33259802

    Open questions at the time
    • Mechanism coupling endosomal PDGFRA to SMAD activation not biochemically resolved
    • Generality of the GSX2 loop to other lineages unknown
  16. 2020 Medium

    Clarified PDGFRA's developmental roles in lineage decisions: chondrocyte progenitor specification via Wnt9a suppression and epicardial fibroblast differentiation.

    Evidence Conditional Pdgfra loss- and gain-of-function mouse models with Wnt pathway rescue; Tbx18-Cre epicardial knockout

    PMID:24000064 PMID:32800757

    Open questions at the time
    • Direct effectors linking PDGFRA to Wnt9a transcription not identified
    • Single-lab findings
  17. 2022 Medium

    Positioned PDGFRA downstream of FLNC loss via β-catenin, implicating receptor activity in a non-cancer cardiomyopathy and validating inhibition as a functional intervention.

    Evidence FLNC-mutant iPSC-cardiomyocytes with Co-IP/proteomics and crenolanib contractility rescue

    PMID:35196083

    Open questions at the time
    • Mechanism of β-catenin-driven PDGFRA activation not defined
    • Co-IP/proteomics axis without reciprocal validation
  18. 2024 High

    Resolved the avapritinib binding mode and a critical Gα sub-pocket, enabling structure-guided design of derivatives against resistance.

    Evidence X-ray crystallography of avapritinib–PDGFRA complexes with derivative pharmacology

    PMID:38167404

    Open questions at the time
    • Clinical efficacy of new derivatives not established
    • Coverage of all resistance mutations not demonstrated
  19. 2025 Medium

    Identified Endocan as a direct extracellular activator of PDGFRA driving Myc-dependent chromatin remodeling, revealing a paracrine route to receptor activation in glioma.

    Evidence Direct binding and phosphorylation assays, ATAC-seq, and Esm1-KO mouse GBM with ponatinib treatment

    PMID:39773984

    Open questions at the time
    • Binding interface on PDGFRA not structurally mapped
    • Relationship to canonical PDGF ligand signaling unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse activation modes (point mutation, extracellular/glycosylation defects, fusions, paracrine ligands, chromatin-level overexpression) differentially shape downstream signaling balance, trafficking, and inhibitor response in a single quantitative framework remains unresolved.
  • No unified structural model of full-length ligand- versus mutation-activated receptor
  • Effector-level differences between activation modes not systematically compared
  • Mechanism coupling endosomal/Golgi trafficking to signaling output incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0060089 molecular transducer activity 2 GO:0001618 virus receptor activity 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005768 endosome 2 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CTNNB1EGFRESM1FIP1L1KDRPTPN11

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 PDGFRA harbors activating intragenic mutations in ~35% of KIT-wild-type GISTs, making KIT and PDGFRA mutations alternative and mutually exclusive oncogenic mechanisms in GISTs; both activate overlapping downstream signaling intermediates. Mutational sequencing of GIST tumors; functional characterization of downstream signaling activation Science High 12522257
2005 PDGFRA exon 12 mutations (e.g., V561D, SPDHE566-571R) and exon 14 substitution (N659K) are imatinib-sensitive, whereas most exon 18 codon D842 substitutions (D842V, RD841-842KI, DI842-843IM) are imatinib-resistant in vitro; D842Y is an exception that retains imatinib sensitivity. Transient expression of PDGFRA mutant isoforms in CHO cells; stable expression in BA/F3 cell lines; proliferation/inhibition assays Journal of Clinical Oncology High 15928335
2010 PDGFRA gene rearrangements, including an intragenic deletion of exons 8 and 9 (PDGFRA-Δ8,9) and a KDR-PDGFRA gene fusion, occur in 40% of PDGFRA-amplified GBMs; both rearrangements produce constitutively elevated tyrosine kinase activity and transforming potential reversible by PDGFR blockade. Genomic analysis of glioma PDGFRA locus; functional assays measuring constitutive kinase activity and transformation; PDGFR inhibitor treatment Genes & Development High 20889717
2016 Crystal structure of the PDGFRA kinase domain in the auto-inhibited form reveals that the juxtamembrane (JM) domain inserts into the active site stabilizing a 'DFG out' (inactive) conformation; Asp842 makes extensive contacts with activation-loop residues to maintain this conformation. The D842V mutation disrupts this stabilization, constitutively activates the kinase, and increases ATP affinity, together explaining imatinib resistance. X-ray crystallography of PDGFRA kinase domain; kinetic measurements of ATP affinity for D842V mutant Biochemical and Biophysical Research Communications High 27349873
2017 BLU-285 (avapritinib), designed to interact preferentially with the active conformation of PDGFRA, potently inhibits the activation-loop mutant PDGFRA D842V with subnanomolar potency, overcoming the resistance seen with type II inhibitors (imatinib) that require the inactive 'DFG out' conformation. In vitro kinase inhibition assays; preclinical cell/animal models; phase 1 clinical evaluation Science Translational Medicine High 29093181
2024 Crystal structures of avapritinib in complex with wild-type and mutant PDGFRA (and KIT) reveal the inhibitor binding mode and identify a sub-pocket (Gα-pocket) critical for inhibitor engagement; this structural information was used to design derivatives that overcome drug resistance. X-ray crystallography of avapritinib–PDGFRA complexes; structure-guided medicinal chemistry and pharmacologic characterization of derivatives Nature Communications High 38167404
2007 The FIP1L1-PDGFRA fusion protein promotes myeloproliferation in human CD34+ hematopoietic progenitors by activating PI3K, ERK1/2, and STAT5 signaling; STAT5 activation is dependent on the FIP1L1 N-terminal domain (aa 30-233), and combined PI3K + ERK1/2 inhibition significantly reverses colony formation. Retroviral transduction of human CD34+ progenitors with FIP1L1-PDGFRA and deletion mutants; phospho-Western blotting; dominant-negative STAT5; pharmacological inhibitors Cancer Research High 17440089
2011 SHP-2 (PTPN11) mediates PDGFRA-driven gliomagenesis: abrogation of the PDGFRA–SHP-2 binding interface or pharmacological SHP-2 inhibition disrupts PI3K interaction with PDGFRA, suppresses downstream AKT/mTOR activation, and impairs tumorigenicity of Ink4a/Arf-null cells; activated PI3K rescues this effect, placing SHP-2 upstream of PI3K/AKT/mTOR. Epistasis via signaling-module mutants of PDGFRA; shRNA knockdown and pharmacological inhibitors of SHP-2; activated PI3K rescue experiment; mouse intracranial glioma model Journal of Clinical Investigation High 21393858
2013 Novel somatic PDGFRA missense mutations and in-frame deletions/insertions in pediatric high-grade gliomas result in ligand-independent receptor activation blocked by PDGFR small-molecule inhibitors; expression of these mutants in p53-null mouse astrocytes confers proliferative advantage and generates HGGs in vivo with complete penetrance. Full coding-sequence sequencing of PDGFRA; in vitro receptor phosphorylation assays; p53-null astrocyte transformation assay; intracranial implantation mouse model Cancer Research High 23970477
2012 ETV6-PDGFRB and FIP1L1-PDGFRA fusion oncogenes activate STAT1, STAT3, STAT5, and NF-κB in human CD34+ hematopoietic progenitors; NF-κB activation is downstream of PI3K, and NF-κB inhibition blocks eosinophil differentiation and expression of eosinophil markers (IL-5 receptor, eosinophil peroxidase). Retroviral transduction of human cord-blood CD34+ cells; phospho-Western blotting; PI3K inhibition; dominant-negative IκB; bortezomib/BMS-345541 treatment; gene expression microarrays Haematologica High 22271894
2018 PDGFRA extracellular domain mutation Y288C results in primary high-mannose glycosylation consistent with ER retention, constitutive dimerization and phosphorylation in the absence of ligand, and constitutive activation of Akt, ERK1/2, and STAT3; this mutant is resistant to PDGFR inhibitors but sensitive to PI3K/mTOR and MEK inhibitors. Characterization of glycosylation state; constitutive phosphorylation assays; dimerization assays; inhibitor sensitivity profiling in cell lines Nature Communications High 30389923
2020 Secondary resistance to avapritinib in PDGFRA-mutant GIST is caused by secondary mutations in PDGFRA exons 13, 14, and 15 (V658A, N659K, Y676C, G680R) that interfere with avapritinib binding; most resistant tumors remain dependent on PDGFRA oncogenic signaling. Tumor and plasma biopsy sequencing from patients progressing on avapritinib or imatinib; functional analysis of resistance mutations Cancer Discovery Medium 32972961
2001 PDGF-A/PDGFRA signaling promotes medulloblastoma cell migration and drives RAS/MAPK pathway activation (dose-dependent phosphorylation of MEK1, MEK2, p42/p44 MAPK); neutralizing antibodies to PDGFRA block MEK/MAPK phosphorylation and inhibit migration. In vitro migration assays; phospho-Western blotting with PDGF-A stimulation; neutralizing antibody blockade; MEK inhibitor (U0126) treatment Nature Genetics Medium 11544480
2008 Activating PDGFRA mutations (exons 12 and 18, including D842V) are found in 70% of inflammatory fibroid polyps, demonstrating that gain-of-function PDGFRA mutations drive neoplastic rather than reactive growth in IFPs. Mutational analysis (PCR + sequencing) of PDGFRA exons 10, 12, 14, 18 in 23 IFPs; FISH for FIP1L1-PDGFRA translocation (negative) Journal of Pathology Medium 18686281
2013 Conditional deletion of Pdgfra in murine epicardium (Tbx18-Cre) prevents differentiation of epicardium-derived cells into mature cardiac fibroblasts, while canonical Wnt, Hh, and Fgfr1/2 signaling are dispensable for epicardial development. Conditional knockout using Tbx18-Cre; cardiac phenotyping Cardiovascular Research Medium 24000064
2016 Pdgfra and Pdgfrb genetically interact during palatogenesis in zebrafish and mouse: double mutants show significantly more severe palatal defects than pdgfra single mutants; in zebrafish, this interaction affects neural crest condensation in maxillary arches without affecting proliferation or cell death. Zebrafish/mouse double mutant genetic epistasis; time-lapse confocal imaging of neural crest condensation; pharmacological Pdgf inhibition Developmental Dynamics Medium 26971580
2020 In CKD, PDGFRA is translocated to early endosomes upon sonic hedgehog overexpression; within the endosome, PDGFRA activates TGFB1/SMAD signaling to promote GMC differentiation into myofibroblasts, ECM deposition, and vascular fibrosis; conditional Pdgfra KO in GLI1+ mesenchymal cells suppresses neointima formation and improves AVF patency. Conditional Pdgfra knockout in GLI1+ cells; subcellular fractionation/immunofluorescence for PDGFRA endosomal localization; SMAD signaling assays; in vivo AVF model in CKD mice JCI Insight Medium 33001865
2020 Pdgfra directs embryonic mesenchymal stem cell differentiation toward chondrocyte progenitors by inhibiting Wnt9a transcription and its downstream beta-catenin signaling; activating Wnt signaling rescues the ectopic cartilage phenotype caused by excessive Pdgfra activity. Tissue-specific conditional Pdgfra knockout and gain-of-function mouse models; Wnt9a expression analysis; rescue experiments with Wnt pathway activation Developmental Biology Medium 32800757
2017 EGFRvIII-driven GBM tumorigenesis requires PDGFRA co-stimulatory signaling; simultaneous pharmacological inhibition of both EGFRvIII and PDGFRA kinases is necessary for anti-tumor efficacy in EGFRvIII-expressing GBM patient-derived xenografts. Genetically engineered autochthonous GBM mouse model; combinatorial kinase inhibitor treatment in PDX models Oncogene Medium 33707748
2017 EGFR functionally transactivates PDGFRA and induces EGFR-PDGFRA receptor heterodimerization in GBM tumor sphere lines; EGF-induced transactivation and heterodimerization are abolished by EGFR inhibitors. Co-immunoprecipitation; phosphorylation assays; EGFR inhibitor treatment; single-cell imaging in GBM tumor sphere lines Scientific Reports Medium 28831081
2014 Cell-surface expression of PDGFRA in glioma cells is negatively regulated by ERK-dependent trafficking: MEK inhibition (U0126) reduces PDGFRA co-localization with endosomal recycling markers (clathrin, RAB11, EEA1) and increases co-localization with the Golgi marker Giantin, diverting PDGFRA from recycling to Golgi retention, reducing surface PDGFRA and glioma cell proliferation. Single-cell imaging; flow cytometry; subcellular co-localization immunofluorescence; MEK inhibitor treatment; glioma cell proliferation assays PloS One Medium 24489888
2022 FLNC deficiency induces nuclear translocation of beta-catenin (CTNNB1), which subsequently activates PDGFRA signaling; this was demonstrated by co-immunoprecipitation and proteomic identification of CTNNB1 as a FLNC downstream target, and pharmacological inhibition of PDGFRA with crenolanib improved contractile function in patient-specific iPSC-derived cardiomyocytes. Patient-specific iPSC-CMs with FLNCtv mutations; FLNC siRNA knockdown; co-immunoprecipitation and proteomics; crenolanib (PDGFRA inhibitor) treatment; contractility measurements Science Advances Medium 35196083
1991 The mouse patch (Ph) mutation carries a deletion encompassing the Pdgfra gene: Ph homozygotes lack Pdgfra genomic sequences and Pdgfra mRNA, establishing that Pdgfra loss-of-function causes the Ph developmental phenotype. Interspecific backcross mapping; RFLP analysis; genomic Southern blotting; RNA analysis of embryos PNAS High 1846043
2017 In alveolar rhabdomyosarcoma, Src family kinases potentiate PDGFRA signaling; acquired resistance to PDGFRA inhibition involves upregulation of Src-Raf-MAPK signaling downstream of PDGFRA; in Pdgfra-knockout tumors, Src inhibition had no effect on viability, establishing PDGFRA as the required nodal point for Src-Raf activity. Kinase inhibitor combinations in primary aRMS cell cultures; Pdgfra knockout tumor cells; in vivo sorafenib treatment of mouse aRMS tumors Biochemical and Biophysical Research Communications Medium 22960170
2025 Endocan (ESM1), an endothelial-secreted proteoglycan, directly binds and activates PDGFRA; subsequent PDGFRA signaling enhances chromatin accessibility at the Myc promoter and upregulates Myc expression, inducing stable phenotypic changes (proliferation, migration, angiogenesis) in GBM cells; ponatinib (PDGFRA inhibitor) increases survival in Esm1 wild-type but not Esm1-knockout mouse GBM model. Direct binding assay of Endocan to PDGFRA; PDGFRA activation/phosphorylation assays; ATAC-seq chromatin accessibility; Myc expression assays; Esm1 KO mouse GBM model with ponatinib treatment Nature Communications Medium 39773984
2017 pdgfra is required for proper medial migration of both endocardial and myocardial precursors during zebrafish cardiac assembly; pdgfra mutants (truncated protein fused with mRFP by gene trapping) display defective endocardial migration to the midline, leading to abnormal myocardial fusion. Gene-trap zebrafish pdgfra mutant; expression analysis; cardiac morphology assessment; endocardial migration imaging Biology Open Medium 28167492
2011 CD140a (PDGFRα) identifies human oligodendrocyte progenitor cells (OPCs) in fetal forebrain as a bipotential mitotic population capable of oligodendrocyte or astrocyte fate specification; CD140a+ cells transplanted into hypomyelinated shiverer mice migrate robustly and myelinate more efficiently than A2B5+ cells. FACS isolation of CD140a+ cells; in vitro differentiation assays; xenotransplantation into shiverer mice; microarray expression analysis Nature Biotechnology Medium 21947029
2020 50% of H3.3 G34R/V gliomas bear co-occurring activating PDGFRA mutations that show strong selection pressure at recurrence; a chromatin loop connecting PDGFRA to GSX2 regulatory elements in interneuron progenitor cells promotes PDGFRA overexpression, and mutant PDGFRA is potently oncogenic while G34R/V can become dispensable for tumor maintenance. Integrated genomic analysis of G34R/V tumor cohort; chromatin conformation (loop) analysis; single-cell transcriptomics; functional oncogenicity assays Cell Medium 33259802

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer cell 5848 20129251
2003 PDGFRA activating mutations in gastrointestinal stromal tumors. Science (New York, N.Y.) 1877 12522257
2005 PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 654 15928335
2001 Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nature genetics 355 11544480
2008 Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology 319 18312355
2006 KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Seminars in diagnostic pathology 223 17193822
1991 Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation. Proceedings of the National Academy of Sciences of the United States of America 206 1846043
2012 Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas. PloS one 190 22389665
2013 Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas. Cancer research 180 23970477
2011 CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells. Nature biotechnology 174 21947029
2019 Benralizumab for PDGFRA-Negative Hypereosinophilic Syndrome. The New England journal of medicine 173 30943337
2010 PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas. Genes & development 171 20889717
2017 A precision therapy against cancers driven by KIT/PDGFRA mutations. Science translational medicine 166 29093181
2006 Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas. Molecular cancer research : MCR 149 17189383
2020 Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis. Cell 140 33259802
2015 KIT and PDGFRA mutations and the risk of GI stromal tumor recurrence. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 135 25605837
2008 Inflammatory fibroid polyps harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene. The Journal of pathology 122 18686281
2008 Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias. Leukemia 122 18843283
2012 miR-34a repression in proneural malignant gliomas upregulates expression of its target PDGFRA and promotes tumorigenesis. PloS one 108 22479456
2008 PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma. Oncogene 82 18679424
2004 Differential expression of KIT/PDGFRA mutant isoforms in epithelioid and mixed variants of gastrointestinal stromal tumors depends predominantly on the tumor site. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 81 15154005
2011 SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humans. The Journal of clinical investigation 75 21393858
2005 Mutation and expression of PDGFRA and KIT in malignant peripheral nerve sheath tumors, and its implications for imatinib sensitivity. Carcinogenesis 73 16357008
2014 Integrated genomic study of quadruple-WT GIST (KIT/PDGFRA/SDH/RAS pathway wild-type GIST). BMC cancer 69 25239601
2009 PDGFRA, PDGFRB, EGFR, and downstream signaling activation in malignant peripheral nerve sheath tumor. Neuro-oncology 67 19246520
2020 Resistance to Avapritinib in PDGFRA-Driven GIST Is Caused by Secondary Mutations in the PDGFRA Kinase Domain. Cancer discovery 65 32972961
2007 Molecular mechanisms underlying FIP1L1-PDGFRA-mediated myeloproliferation. Cancer research 62 17440089
2016 Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma. Oncotarget 60 27582545
2019 Myxoid glioneuronal tumor, PDGFRA p.K385-mutant: clinical, radiologic, and histopathologic features. Brain pathology (Zurich, Switzerland) 56 31609499
2021 Myeloid/Lymphoid Neoplasms Associated With Eosinophilia and Rearrangements of PDGFRA, PDGFRB, or FGFR1 or With PCM1-JAK2. American journal of clinical pathology 55 33367495
2021 Early and Next-Generation KIT/PDGFRA Kinase Inhibitors and the Future of Treatment for Advanced Gastrointestinal Stromal Tumor. Frontiers in oncology 53 34322383
2007 Molecular analysis of c-Kit and PDGFRA in GISTs diagnosed by EUS. American journal of clinical pathology 52 17145623
2018 Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies. Nature communications 51 30389923
2022 CircCDK14 Promotes Tumor Progression and Resists Ferroptosis in Glioma by Regulating PDGFRA. International journal of biological sciences 50 35002529
2013 Myeloid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, and FGFR1: a review. International journal of laboratory hematology 50 23489324
2016 Structural and biochemical studies of the PDGFRA kinase domain. Biochemical and biophysical research communications 48 27349873
2015 PDGFRA-mutant syndrome. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 48 25975287
2009 Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma. BMC cancer 48 19563658
2012 ETV6-PDGFRB and FIP1L1-PDGFRA stimulate human hematopoietic progenitor cell proliferation and differentiation into eosinophils: the role of nuclear factor-κB. Haematologica 44 22271894
2015 Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. American journal of clinical pathology 41 26276769
2008 Molecular drug targets in myeloproliferative neoplasms: mutant ABL1, JAK2, MPL, KIT, PDGFRA, PDGFRB and FGFR1. Journal of cellular and molecular medicine 41 19175693
2016 Human Non-Hematopoietic CD271pos/CD140alow/neg Bone Marrow Stroma Cells Fulfill Stringent Stem Cell Criteria in Serial Transplantations. Stem cells and development 40 27527928
2009 Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs. Histopathology 39 19614767
2013 Epicardial function of canonical Wnt-, Hedgehog-, Fgfr1/2-, and Pdgfra-signalling. Cardiovascular research 37 24000064
2017 EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines. Scientific reports 35 28831081
2016 Pdgfra and Pdgfrb genetically interact during craniofacial development. Developmental dynamics : an official publication of the American Association of Anatomists 35 26971580
2013 CD133/CD140a-based isolation of distinct human multipotent neural progenitor cells and oligodendrocyte progenitor cells. Stem cells and development 35 23488628
2025 Effective targeting of PDGFRA-altered high-grade glioma with avapritinib. Cancer cell 34 40086436
2020 PDGFRA in vascular adventitial MSCs promotes neointima formation in arteriovenous fistula in chronic kidney disease. JCI insight 32 33001865
2017 MiR-491-5p negatively regulates cell proliferation and motility by targeting PDGFRA in prostate cancer. American journal of cancer research 32 29312807
2014 C-kit and PDGFRA gene mutations in triple negative breast cancer. International journal of clinical and experimental pathology 32 25120810
2020 Autophagy inhibition blunts PDGFRA adipose progenitors' cell-autonomous fibrogenic response to high-fat diet. Autophagy 30 31992125
2020 Pdgfra regulates multipotent cell differentiation towards chondrocytes via inhibiting Wnt9a/beta-catenin pathway during chondrocranial cartilage development. Developmental biology 30 32800757
2009 Amplification and overexpression of KIT, PDGFRA, and VEGFR2 in medulloblastomas and primitive neuroectodermal tumors. Journal of neuro-oncology 30 19779861
2022 An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors. Frontiers in oncology 29 36119525
2019 Circulating cKIT and PDGFRA DNA indicates disease activity in Gastrointestinal Stromal Tumor (GIST). International journal of cancer 29 30882891
2014 Glioma cell proliferation controlled by ERK activity-dependent surface expression of PDGFRA. PloS one 28 24489888
2007 Site-dependent differential KIT and PDGFRA expression in gastric and intestinal gastrointestinal stromal tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 28 17673922
1992 Deletion of the KIT and PDGFRA genes in a patient with piebaldism. American journal of medical genetics 28 1279971
2016 Concomitant KIT/BRAF and PDGFRA/BRAF mutations are rare events in gastrointestinal stromal tumors. Oncotarget 27 27097112
2015 Classification of KIT/PDGFRA wild-type gastrointestinal stromal tumors: implications for therapy. Expert review of anticancer therapy 27 25831232
2012 Genetic variants near PDGFRA are associated with corneal curvature in Australians. Investigative ophthalmology & visual science 27 22969067
2019 Gain of FGF4 is a frequent event in KIT/PDGFRA/SDH/RAS-P WT GIST. Genes, chromosomes & cancer 26 30887595
2010 Clinical implications of KIT and PDGFRA genotyping in GIST. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 26 20947481
2022 Activation of PDGFRA signaling contributes to filamin C-related arrhythmogenic cardiomyopathy. Science advances 24 35196083
2018 Familial PDGFRA-mutation syndrome: somatic and gastrointestinal phenotype. Human pathology 24 29486293
1998 Specific expression in mouse mesoderm- and neural crest-derived tissues of a human PDGFRA promoter/lacZ transgene. Mechanisms of development 23 9510033
1995 A 1.8-Mb YAC contig spanning three members of the receptor tyrosine kinase gene family (Pdgfra, Kit, and Flk1) on mouse chromosome 5. Genomics 23 7540588
2024 Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA. Nature communications 22 38167404
2022 High frequency of PDGFRA and MUC family gene mutations in diffuse hemispheric glioma, H3 G34-mutant: a glimmer of hope? Journal of translational medicine 22 35109850
2017 Characterization and Targeting of Platelet-Derived Growth Factor Receptor alpha (PDGFRA) in Inflammatory Breast Cancer (IBC). Neoplasia (New York, N.Y.) 22 28609680
2023 KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial. Clinical cancer research : an official journal of the American Association for Cancer Research 21 37014660
2023 Functional Pdgfra fibroblast heterogeneity in normal and fibrotic mouse lung. JCI insight 21 37824216
2012 An immunohistochemical and molecular genetic analysis of KIT and PDGFRA in small cell lung carcinoma in Japanese. International journal of clinical and experimental pathology 21 22670177
2023 Expanding the spectrum of tyrosine kinase fusions in calcified chondroid mesenchymal neoplasms: Identification of a novel PDGFRA::USP8 gene fusion. Genes, chromosomes & cancer 20 37642440
2021 EGFRvIII tumorigenicity requires PDGFRA co-signaling and reveals therapeutic vulnerabilities in glioblastoma. Oncogene 20 33707748
2022 Polygenic risk impacts PDGFRA mutation penetrance in non-syndromic cleft lip and palate. Human molecular genetics 19 35147171
2011 Differential expression of neural markers in KIT and PDGFRA wild-type gastrointestinal stromal tumours. Histopathology 19 22175887
2022 PDGFRA Immunohistochemistry Predicts PDGFRA Mutations in Gastrointestinal Stromal Tumors. The American journal of surgical pathology 18 33859072
2018 CDK4/6 and PDGFRA Signaling as Therapeutic Targets in Diffuse Intrinsic Pontine Glioma. Frontiers in oncology 18 29904623
2013 Diagnostic significance of DOG-1 and PKC-θ expression and c-Kit/PDGFRA mutations in gastrointestinal stromal tumours. Scandinavian journal of gastroenterology 18 23862765
2024 Molecular and clinicopathological features of KIT/PDGFRA wild-type gastrointestinal stromal tumors. Cancer science 17 38178783
2024 KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem. Expert opinion on investigational drugs 17 38344849
2020 Immune Cell Infiltration and the Expression of PD-1 and PD-L1 in Primary PDGFRA-Mutant Gastrointestinal Stromal Tumors. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 17 33169322
2011 Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors. Gut and liver 17 21814597
2020 Guinea pig cytomegalovirus trimer complex gH/gL/gO uses PDGFRA as universal receptor for cell fusion and entry. Virology 16 32791352
2018 PDGFRA mRNA overexpression is associated with regional metastasis and reduced survival in oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 16 29660835
2017 Disruption of pdgfra alters endocardial and myocardial fusion during zebrafish cardiac assembly. Biology open 16 28167492
2017 Succinate dehydrogenase deficiency in a PDGFRA mutated GIST. BMC cancer 16 28768491
2012 An adaptive Src-PDGFRA-Raf axis in rhabdomyosarcoma. Biochemical and biophysical research communications 16 22960170
2022 JUN and PDGFRA as Crucial Candidate Genes for Childhood Autism Spectrum Disorder. Frontiers in neuroinformatics 15 35655651
2021 The role of PDGFRA as a therapeutic target in young colorectal cancer patients. Journal of translational medicine 15 34702313
2012 Expression of DOG1, CD117 and PDGFRA in gastrointestinal stromal tumors and correlations with clinicopathology. Asian Pacific journal of cancer prevention : APJCP 15 22799337
2023 Valtrate, an iridoid compound in Valeriana, elicits anti-glioblastoma activity through inhibition of the PDGFRA/MEK/ERK signaling pathway. Journal of translational medicine 14 36829235
2023 Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche. Nature communications 14 38042929
2015 Analysis of mutation of the c-Kit gene and PDGFRA in gastrointestinal stromal tumors. Experimental and therapeutic medicine 14 26622437
2022 Association of MTOR and PDGFRA gene polymorphisms with different degrees of myopia severity. Experimental eye research 13 35090889
2016 Intratumoral KIT mutational heterogeneity and recurrent KIT/ PDGFRA mutations in KIT/PDGFRA wild-type gastrointestinal stromal tumors. Oncotarget 13 26848617
2008 Haplotype-specific expression of the human PDGFRA gene correlates with the risk of glioblastomas. International journal of cancer 13 18464291
2025 Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma. Nature communications 12 39773984

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