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PDGFB platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)

Identity

Other namesV-sis platelet-derived growth factor beta (simian sarcoma viral oncogene homolog)
HGNC (Hugo) PDGFB
LocusID (NCBI) 5155
Location 22q13.1
Location_base_pair Starts at 39619685 and ends at 39640957 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Telomeric to TXN2 (thioredoxin, mitochondrial), centromeric to DMC1(dosage suppressor of mck1, yeast homologue meiosis-specific homologous recombination)

DNA/RNA

 
Description The PDGFB gene encodes the human platelet-derived growth factor (PDGF) B chain precursor and is the cellular homologue of the v-sis oncogene. PDGFB gene is 22 kb in size and is composed of 7 exons. The exon 7 and most part of the exon 1 are non coding sequences (white boxes).
Transcription The PDGFB chain precursor is usually translated from a 3.5 kb transcript. The first exon contains the sequence for the signal peptide preceeded by a 1 kb-long untranslated sequence with potent translation inhibitory activity. A 2.6 kb mRNA which initiates at an alternative exon 1, exon 1A, was described in the human choriocarcinoma cell line JEG-3. It initiates an open reading frame that is continuous with the code for the PDGF B chain precursor but lacks the code for the signal peptide.

Protein

 
Description The PDGFB chains are synthesised as 240 amino acids precursors molecules containing amino and carboxy-terminal propeptides, which are removed by site-specific endopeptidases. Two PDGFB precursor chains associate in dimers to form the mature PDGFBB after proteolysis.
Expression First isolated from human platelets, the PDGFBB is synthesized by a variety of different cell lineages.
Localisation Secreted in the extra-cellular medium
Function The homodimer PDGFBB is a potent growth factor that acts as a mitogen and chemo-attractant for a variety of cells from mesenchymal origin. It has various roles in embryonic development, tissue regeneration, osteogenesis, fibrosis, atherosclerosis, and neoplasia.
Homology Member of the PDGF/VEGF family

Implicated in

Entity
  • Dermatofibrosarcoma Protuberans (DP), also called Darier Ferrand tumour or Darier-Hoffmann tumour.
  • Giant cell fibrosarcoma (GCF) (juvenile form of DP).
  • Bednar tumour (pigmented variant of DP)
  • Disease Infiltrative skin tumours of intermediate malignancy
    Prognosis The prognosis is usually favourable. These tumours are locally aggressive and highly recurrent, but metastases or tumour-related deaths are extremely rare.
    Cytogenetics Dermatofibrosarcoma Protuberans, Giant Cell fibrosarcoma and Bednar tumours present specific cytogenetic features such as reciprocal translocations t(17;22)(q22;q13.1) ( Fig A) or, more often, supernumerary ring chromosomes derived from t(17;22) (B). As shown by FISH analysis, the ring chromosomes contain chromosome 22 centromere and low-level amplification of 22cen-q13.1 and 17q22-qter sequences. To note, in most cases, the derivative chromosome 17 is not present. In contrast, several copies of the derivative chromosome 22 are generally observed.in addition to two apparently normal chromosomes 17
     
    Hybrid/Mutated Gene
  • Both rings and der(22) translocated chromosomes present a same molecular rearrangement that fuses the collagen type I alpha 1(COL1A1) and the platelet-derived growth factor B chain (PDGFB) genes (C).
  • In all DP and GCF cases studied, the t(17;22)translocation results in chimerical COL1A1/PDGFB mRNA production, in which the PDGFB exon 1 is deleted and replaced by a variable segment of COL1A1 mRNA sequence. In the 32 cases tested the fusion mRNA was an in-frame fusion of one of the COL1A1 exons (varying from exon 7 to exon 47) to PDGFB exon 2 (D).
  • Abnormal Protein
  • COL1A1 and PDGFB are both encoded as pro-peptides, which are processed by proteolytic cleavage at N and C-terminus, to give mature proteins. Sequences analyses of the chimerical COL1A1/PDGFB fusion transcripts showed that the COL1A1/PDGFB putative proteins displayed a pro-peptide structure, which preserved the N-terminus COL1A1 pro-peptide containing the signal peptide and the N and C-terminus PDGFB maturation cleavage sites.
  • The functional and structural properties of the COL1A1/PDGFB fusion protein were characterized by generating stable fibroblastic cell lines that expressed tumour-derived COL1A1/PDGFB chimerical genes. The diagram herein given presents the COL1A1/PDGFB chimerical protein encoded by the T94796 tumour-derived chimerical COL1A1/PDGFB cDNA sequence
  •  
    A chimerical COL1A1/PDGFB cDNA sequence fusing COL1A1 exon 29 to PDGFB exon 2 was isolated from the DP T94796 tumour and stably transfected in the Chinese hamster lung fibroblastic cell line PS200 (E).
    The T94796 COL1A1/PDGFB chimerical protein sequence retained the COL1A1 N-terminus processing site encoded by the COL1A1 exon 6 and the N and C-terminus PDGFB processing sites encoded by the PDGFB exons 3 and 6 respectively (F).
    Mutagenesis experiments and immunodetection with anti-PDGFBB and specific anti-COL1A1/PDGFB antibodies showed that COL1A1/PDGFB expressing cells produced 116 kD chimerical COL1A1/PDGFB precursors chains, which formed dimers and were processed to give active 30 kD PDGFB-like dimers (G).
    Oncogenesis
  • Transfected cells lines expressing the chimerical T94796-COL1A1/PDGFB proteins became independent upon growth factors, including PDGFB, and induced tumours formation in nude mice. In addition, it was shown that the COL1A1/PDGFB stable clones cells contained activated PDGF b-receptors and that the conditioned media from COL1A1/PDGFB transfected cells were able to stimulate fibroblastic cells growth. Anti-PDGFBB antibodies neutralized this effect.
  • These results strongly suggest that the COL1A1/PDGFB chimerical gene expression associated with DP, contributes to tumour formation through ectopic production of mature PDGFB and the formation of an autocrine loop.
  •   

    Breakpoints

     

    Other Leukemias implicated (Data extracted from papers in the Atlas)

    Leukemias t0817q24q22ID1494 t1119q23p13ID1540 t614p25q32IRF4IGHID1175 t1213p13q14ID1323 t1117q23q12AF17ID1027
    t1117p15p13ID2134 t1114ID1070

    Other Solid tumors implicated (Data extracted from papers in the Atlas)

    Solid Tumors ProstateOverviewID5041 ProstateOverviewID5041 ProstateOverviewID5041

    External links

    Nomenclature
    HGNC (Hugo)PDGFB   8800
    Cards
    AtlasPDGFBID155
    Entrez_Gene (NCBI)PDGFB  5155  platelet-derived growth factor beta polypeptide
    GeneCards (Weizmann)PDGFB
    Ensembl (Hinxton)ENSG00000100311 [Gene_View]  chr22:39619685-39640957 [Contig_View]  PDGFB [Vega]
    ICGC DataPortalENSG00000100311
    cBioPortalPDGFB
    AceView (NCBI)PDGFB
    Genatlas (Paris)PDGFB
    WikiGenes5155
    SOURCE (Princeton)NM_002608 NM_033016
    Genomic and cartography
    GoldenPath (UCSC)PDGFB  -  22q13.1   chr22:39619685-39640957 -  22q13.1   [Description]    (hg19-Feb_2009)
    EnsemblPDGFB - 22q13.1 [CytoView]
    Mapping of homologs : NCBIPDGFB [Mapview]
    OMIM190040   
    Gene and transcription
    Genbank (Entrez)AK022920 BC029822 BC077725 BM983641 CR456538
    RefSeq transcript (Entrez)NM_002608 NM_033016
    RefSeq genomic (Entrez)AC_000154 NC_000022 NC_018933 NG_012111 NT_011520 NW_001838745 NW_004929430
    Consensus coding sequences : CCDS (NCBI)PDGFB
    Cluster EST : UnigeneHs.1976 [ NCBI ]
    CGAP (NCI)Hs.1976
    Alternative Splicing : Fast-db (Paris)GSHG0020405
    Alternative Splicing GalleryENSG00000100311
    Gene ExpressionPDGFB [ NCBI-GEO ]     PDGFB [ SEEK ]   PDGFB [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP01127 (Uniprot)
    NextProtP01127  [Medical]
    With graphics : InterProP01127
    Splice isoforms : SwissVarP01127 (Swissvar)
    Domaine pattern : Prosite (Expaxy)PDGF_1 (PS00249)    PDGF_2 (PS50278)   
    Domains : Interpro (EBI)PD_growth_factor_CS [organisation]   PDGF/VEGF_dom [organisation]   PDGF_N [organisation]  
    Related proteins : CluSTrP01127
    Domain families : Pfam (Sanger)PDGF (PF00341)    PDGF_N (PF04692)   
    Domain families : Pfam (NCBI)pfam00341    pfam04692   
    Domain families : Smart (EMBL)PDGF (SM00141)  
    DMDM Disease mutations5155
    Blocks (Seattle)P01127
    PDB (SRS)1PDG    3MJG    4HQU    4HQX   
    PDB (PDBSum)1PDG    3MJG    4HQU    4HQX   
    PDB (IMB)1PDG    3MJG    4HQU    4HQX   
    PDB (RSDB)1PDG    3MJG    4HQU    4HQX   
    Human Protein AtlasENSG00000100311 [gene] [tissue] [antibody] [cell] [cancer]
    Peptide AtlasP01127
    HPRD01815
    IPIIPI00000044   IPI00334195   IPI00872126   IPI00877974   
    Protein Interaction databases
    DIP (DOE-UCLA)P01127
    IntAct (EBI)P01127
    FunCoupENSG00000100311
    BioGRIDPDGFB
    InParanoidP01127
    Interologous Interaction database P01127
    IntegromeDBPDGFB
    STRING (EMBL)PDGFB
    Ontologies - Pathways
    Ontology : AmiGOGolgi membrane  response to hypoxia  embryonic placenta development  positive regulation of endothelial cell proliferation  monocyte chemotaxis  platelet degranulation  positive regulation of glomerular filtration  platelet-derived growth factor receptor binding  platelet-derived growth factor receptor binding  platelet-derived growth factor receptor binding  platelet-derived growth factor receptor binding  protein binding  collagen binding  extracellular region  extracellular region  extracellular space  cytoplasm  endoplasmic reticulum lumen  DNA replication  protein phosphorylation  substrate-dependent cell migration  epidermal growth factor receptor signaling pathway  transforming growth factor beta receptor signaling pathway  heart development  blood coagulation  growth factor activity  positive regulation of cell proliferation  fibroblast growth factor receptor signaling pathway  response to wounding  response to wounding  cell surface  negative regulation of phosphatidylinositol biosynthetic process  negative regulation of platelet activation  positive regulation of phosphatidylinositol 3-kinase cascade  positive regulation of smooth muscle cell migration  cell growth  superoxide-generating NADPH oxidase activator activity  basolateral plasma membrane  peptidyl-serine phosphorylation  peptidyl-tyrosine phosphorylation  cell projection assembly  actin cytoskeleton organization  hemopoiesis  platelet activation  extracellular matrix organization  positive regulation of cell migration  negative regulation of cell migration  platelet alpha granule lumen  positive regulation of protein autophosphorylation  activation of protein kinase activity  activation of protein kinase B activity  response to estradiol  response to insulin  positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway  paracrine signaling  Fc-epsilon receptor signaling pathway  chemoattractant activity  response to drug  protein homodimerization activity  positive regulation of MAP kinase activity  positive regulation of MAPK cascade  positive regulation of blood vessel endothelial cell migration  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  positive regulation of cyclin-dependent protein kinase activity  positive regulation of DNA replication  positive regulation of fibroblast growth factor receptor signaling pathway  positive regulation of mitosis  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  protein heterodimerization activity  platelet-derived growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  positive regulation of fibroblast proliferation  platelet-derived growth factor binding  blood vessel morphogenesis  positive regulation of smooth muscle cell proliferation  positive regulation of peptidyl-tyrosine phosphorylation  positive chemotaxis  positive regulation of chemotaxis  positive regulation of cell division  cell chemotaxis  branching involved in salivary gland morphogenesis  epithelial cell proliferation involved in salivary gland morphogenesis  positive regulation of protein tyrosine kinase activity  positive regulation of ERK1 and ERK2 cascade  cellular response to growth factor stimulus  cellular response to mycophenolic acid  positive regulation of glomerular mesangial cell proliferation  metanephric glomerular mesangial cell development  metanephric glomerular mesangial cell proliferation involved in metanephros development  metanephric glomerular endothelium development  reactive oxygen species metabolic process  positive regulation of calcium ion import  positive regulation of hyaluronan biosynthetic process  positive regulation of reactive oxygen species metabolic process  positive regulation of DNA biosynthetic process  positive regulation of metanephric mesenchymal cell migration  
    Ontology : EGO-EBIGolgi membrane  response to hypoxia  embryonic placenta development  positive regulation of endothelial cell proliferation  monocyte chemotaxis  platelet degranulation  positive regulation of glomerular filtration  platelet-derived growth factor receptor binding  platelet-derived growth factor receptor binding  platelet-derived growth factor receptor binding  platelet-derived growth factor receptor binding  protein binding  collagen binding  extracellular region  extracellular region  extracellular space  cytoplasm  endoplasmic reticulum lumen  DNA replication  protein phosphorylation  substrate-dependent cell migration  epidermal growth factor receptor signaling pathway  transforming growth factor beta receptor signaling pathway  heart development  blood coagulation  growth factor activity  positive regulation of cell proliferation  fibroblast growth factor receptor signaling pathway  response to wounding  response to wounding  cell surface  negative regulation of phosphatidylinositol biosynthetic process  negative regulation of platelet activation  positive regulation of phosphatidylinositol 3-kinase cascade  positive regulation of smooth muscle cell migration  cell growth  superoxide-generating NADPH oxidase activator activity  basolateral plasma membrane  peptidyl-serine phosphorylation  peptidyl-tyrosine phosphorylation  cell projection assembly  actin cytoskeleton organization  hemopoiesis  platelet activation  extracellular matrix organization  positive regulation of cell migration  negative regulation of cell migration  platelet alpha granule lumen  positive regulation of protein autophosphorylation  activation of protein kinase activity  activation of protein kinase B activity  response to estradiol  response to insulin  positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway  paracrine signaling  Fc-epsilon receptor signaling pathway  chemoattractant activity  response to drug  protein homodimerization activity  positive regulation of MAP kinase activity  positive regulation of MAPK cascade  positive regulation of blood vessel endothelial cell migration  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  positive regulation of cyclin-dependent protein kinase activity  positive regulation of DNA replication  positive regulation of fibroblast growth factor receptor signaling pathway  positive regulation of mitosis  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  protein heterodimerization activity  platelet-derived growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  positive regulation of fibroblast proliferation  platelet-derived growth factor binding  blood vessel morphogenesis  positive regulation of smooth muscle cell proliferation  positive regulation of peptidyl-tyrosine phosphorylation  positive chemotaxis  positive regulation of chemotaxis  positive regulation of cell division  cell chemotaxis  branching involved in salivary gland morphogenesis  epithelial cell proliferation involved in salivary gland morphogenesis  positive regulation of protein tyrosine kinase activity  positive regulation of ERK1 and ERK2 cascade  cellular response to growth factor stimulus  cellular response to mycophenolic acid  positive regulation of glomerular mesangial cell proliferation  metanephric glomerular mesangial cell development  metanephric glomerular mesangial cell proliferation involved in metanephros development  metanephric glomerular endothelium development  reactive oxygen species metabolic process  positive regulation of calcium ion import  positive regulation of hyaluronan biosynthetic process  positive regulation of reactive oxygen species metabolic process  positive regulation of DNA biosynthetic process  positive regulation of metanephric mesenchymal cell migration  
    Pathways : BIOCARTATranscriptional activation of dbpb from mRNA [Genes]   
    Pathways : KEGGMAPK signaling pathway    Ras signaling pathway    Rap1 signaling pathway    Cytokine-cytokine receptor interaction    PI3K-Akt signaling pathway    Focal adhesion    Gap junction    Regulation of actin cytoskeleton    HTLV-I infection    Pathways in cancer    MicroRNAs in cancer    Renal cell carcinoma    Glioma    Prostate cancer    Melanoma   
    Protein Interaction DatabasePDGFB
    Wikipedia pathwaysPDGFB
    Gene fusion - rearrangments
    Rearrangement : COSMICCOL1A1 [17q21.33]  -  PDGFB [22q13.1]  
      [COSF1285] [COSF1286] [COSF1289] [COSF1290] [COSF1291] [COSF1292] [COSF1293] [COSF1294] [COSF531] 
      [COSF532] [COSF533] [COSF534] [COSF535] [COSF536] [COSF537] [COSF538] [COSF539] 
      [COSF540] [COSF541] [COSF542] [COSF543] [COSF544] [COSF545] [COSF546] [COSF547] 
      [COSF548] [COSF549] [COSF550] [COSF551] [COSF552] [COSF553] [COSF554] [COSF555] 
      [COSF556] [COSF557] [COSF558] [COSF559] [COSF560] [COSF561] [COSF562] [COSF563] 
      [COSF564] [COSF565] [COSF591] [COSF592] [COSF593] [COSF594] [COSF595] [COSF596] 
      [COSF597] [COSF598] [COSF599] [COSF600] [COSF601] [COSF602] [COSF603] [COSF604] 
      [COSF605] [COSF606] [COSF607] [COSF608] [COSF626] [COSF627] [COSF634] [COSF635] 
      [COSF636] [COSF637] [COSF638] [COSF639] [COSF640] [COSF641] [COSF642] [COSF643] 
      [COSF644] [COSF645] [COSF646] [COSF647] [COSF648] [COSF649] [COSF650] [COSF651] 
      [COSF652] [COSF653] [COSF654] [COSF655] [COSF656] [COSF815] [COSF816] [COSF817] 
      [COSF818] [COSF819] [COSF820] 
    Rearrangement : TICdbCOL1A1 [17q21.33]  -  PDGFB [13q12.2]
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)PDGFB
    snp3D : Map Gene to Disease5155
    SNP (GeneSNP Utah)PDGFB
    SNP : HGBasePDGFB
    Genetic variants : HAPMAPPDGFB
    Exome VariantPDGFB
    1000_GenomesPDGFB 
    ICGC programENSG00000100311 
    Cancer Gene: CensusPDGFB 
    Somatic Mutations in Cancer : COSMICPDGFB 
    CONAN: Copy Number AnalysisPDGFB 
    Mutations and Diseases : HGMDPDGFB
    Genomic VariantsPDGFB  PDGFB [DGVbeta]
    dbVarPDGFB
    ClinVarPDGFB
    Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
    Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
    Diseases
    OMIM190040   
    MedgenPDGFB
    GENETestsPDGFB
    Disease Genetic AssociationPDGFB
    Huge Navigator PDGFB [HugePedia]  PDGFB [HugeCancerGEM]
    General knowledge
    Homologs : HomoloGenePDGFB
    Homology/Alignments : Family Browser (UCSC)PDGFB
    Phylogenetic Trees/Animal Genes : TreeFamPDGFB
    Chemical/Protein Interactions : CTD5155
    Chemical/Pharm GKB GenePA33145
    Clinical trialPDGFB
    Cancer Resource (Charite)ENSG00000100311
    Other databases
    Probes
    Litterature
    PubMed227 Pubmed reference(s) in Entrez
    CoreMinePDGFB
    iHOPPDGFB

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    Ring 22 chromosomes in dermatofibrosarcoma protuberans are low-level amplifiers of chromosome 17 and 22 sequences.
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    Various regions within the alpha-helical domain of the COL1A1 gene are fused to the second exon of the PDGFB gene in dermatofibrosarcomas and giant-cell fibroblastomas.
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    REVIEW articlesautomatic search in PubMed
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    Contributor(s)

    Written02-2001Marie-Pierre Simon, Georges Maire, Florence Pedeutour

    Citation

    This paper should be referenced as such :
    Simon, MP ; Maire, G ; Pedeutour, F
    PDGFB (platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog))
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):93-97.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/PDGFBID155.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Fri Jul 11 16:52:58 CEST 2014

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