PDGFB

Identity

Other names	V-sis platelet-derived growth factor beta (simian sarcoma viral oncogene homolog)
Hugo	PDGFB
Location	22q12.3-q13.1
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

External links

	Nomenclature
Hugo	PDGFB
GDB	PDGFB
Entrez_Gene	PDGFB  5155  platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)
	Cards
Atlas	PDGFBID155
GeneCards	PDGFB
Ensembl	PDGFB [Search_View]   ENSG00000100311 [Gene_View]
Genatlas	PDGFB
GeneLynx	PDGFB
eGenome	PDGFB
euGene	5155
	Genomic and cartography
GoldenPath	PDGFB  -     chr22:37949665-37966865 -  22q13.1   [Description]    (hg18-Mar_2006)
Ensembl	PDGFB - 22q13.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	PDGFB
	Gene and transcription
Genbank	AK022920 [ ENTREZ ]
Genbank	BC029822 [ ENTREZ ]
Genbank	BC077725 [ ENTREZ ]
Genbank	CR456538 [ ENTREZ ]
Genbank	CR541807 [ ENTREZ ]
RefSeq	NM_002608 [ SRS ]    NM_002608 [ ENTREZ ]
RefSeq	NM_033016 [ SRS ]    NM_033016 [ ENTREZ ]
RefSeq	AC_000065 [ SRS ]    AC_000065 [ ENTREZ ]
RefSeq	AC_000154 [ SRS ]    AC_000154 [ ENTREZ ]
RefSeq	NC_000022 [ SRS ]    NC_000022 [ ENTREZ ]
RefSeq	NT_011520 [ SRS ]    NT_011520 [ ENTREZ ]
RefSeq	NW_001838745 [ SRS ]    NW_001838745 [ ENTREZ ]
RefSeq	NW_927628 [ SRS ]    NW_927628 [ ENTREZ ]
AceView	PDGFB AceView - NCBI
Unigene	Hs.1976 [ SRS ]    Hs.1976 [ NCBI ]     HS1976 [ spliceNest ]
Fast-db	6207 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P01127 [ SRS]    P01127 [ EXPASY ]     P01127 [ INTERPRO ]
Prosite	PS00249 PDGF_1 [ SRS ]    PS00249 PDGF_1 [ Expasy ]
Prosite	PS50278 PDGF_2 [ SRS ]    PS50278 PDGF_2 [ Expasy ]
Interpro	IPR002400 GF_cysknot [ SRS ]    IPR002400 GF_cysknot [ EBI ]
Interpro	IPR000072 PD_growth_factor [ SRS ]    IPR000072 PD_growth_factor [ EBI ]
Interpro	IPR015583 PDGF_B [ SRS ]    IPR015583 PDGF_B [ EBI ]
Interpro	IPR006782 PDGF_N [ SRS ]    IPR006782 PDGF_N [ EBI ]
CluSTr	P01127
Pfam	PF00341 PDGF [ SRS ]    PF00341 PDGF [ Sanger ]    pfam00341 [ NCBI-CDD ]
Pfam	PF04692 PDGF_N [ SRS ]    PF04692 PDGF_N [ Sanger ]    pfam04692 [ NCBI-CDD ]
Smart	SM00141 PDGF [EMBL]
Prodom	PD001629 PD_growth_factor[INRA-Toulouse]
Prodom	P01127 PDGFB_HUMAN [ Domain structure ]   P01127 PDGFB_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P01127
PDB	PDGFB [ SRS ]    PDGFB [ PdbSum ],   PDGFB [ IMB ]   PDGFB [ RSDB ]
HPRD	01815
	Protein Interaction databases
DIP	P01127
IntAct	P01127
	Polymorphism : SNP, mutations, diseases
OMIM	190040    [ map ]
GENECLINICS	190040
SNP	PDGFB [dbSNP-NCBI]
SNP	NM_002608 [SNP-NCI]
SNP	NM_033016 [SNP-NCI]
SNP	PDGFB [GeneSNPs - Utah]  PDGFB] [HGBASE - SRS]
HAPMAP	PDGFB [HAPMAP]
COSMIC	PDGFB [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	PDGFB [Translocation breakpoints In Cancer]
HGMD	PDGFB
	General knowledge
Family Browser	PDGFB [UCSC Family Browser]
SOURCE	NM_002608
SOURCE	NM_033016
SMD	Hs.1976
SAGE	Hs.1976
GO	positive regulation of endothelial cell proliferation [Amigo]  positive regulation of endothelial cell proliferation
GO	platelet-derived growth factor receptor binding [Amigo]  platelet-derived growth factor receptor binding
GO	protein binding [Amigo]  protein binding
GO	extracellular region [Amigo]  extracellular region
GO	extracellular region [Amigo]  extracellular region
GO	growth factor activity [Amigo]  growth factor activity
GO	cell proliferation [Amigo]  cell proliferation
GO	response to wounding [Amigo]  response to wounding
GO	cell surface [Amigo]  cell surface
GO	negative regulation of phosphatidylinositol biosynthetic process [Amigo]  negative regulation of phosphatidylinositol biosynthetic process
GO	negative regulation of platelet activation [Amigo]  negative regulation of platelet activation
GO	positive regulation of smooth muscle cell migration [Amigo]  positive regulation of smooth muscle cell migration
GO	membrane [Amigo]  membrane
GO	platelet dense granule lumen [Amigo]  platelet dense granule lumen
GO	protein homodimerization activity [Amigo]  protein homodimerization activity
GO	positive regulation of MAP kinase activity [Amigo]  positive regulation of MAP kinase activity
GO	cell surface binding [Amigo]  cell surface binding
GO	positive regulation of blood vessel endothelial cell migration [Amigo]  positive regulation of blood vessel endothelial cell migration
GO	positive regulation of DNA replication [Amigo]  positive regulation of DNA replication
GO	protein heterodimerization activity [Amigo]  protein heterodimerization activity
GO	platelet-derived growth factor receptor signaling pathway [Amigo]  platelet-derived growth factor receptor signaling pathway
GO	positive regulation of fibroblast proliferation [Amigo]  positive regulation of fibroblast proliferation
GO	platelet-derived growth factor binding [Amigo]  platelet-derived growth factor binding
GO	positive regulation of chemotaxis [Amigo]  positive regulation of chemotaxis
BIOCARTA	Transcriptional activation of dbpb from mRNA    [Genes]
KEGG	MAPK signaling pathway
KEGG	Cytokine-cytokine receptor interaction
KEGG	Focal adhesion
KEGG	Gap junction
KEGG	Regulation of actin cytoskeleton
PubGene	PDGFB
TreeFam	PDGFB
CTD	5155 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	PDGFB Related clones (RZPD - Berlin)
	PubMed
PubMed	119 Pubmed reference(s) in LocusLink

Bibliography

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Ring 22 chromosomes in dermatofibrosarcoma protuberans are low-level amplifiers of chromosome 17 and 22 sequences.

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PMID 8599739

Translocation, t(17;22)(q22;q13), in dermatofibrosarcoma protuberans: a new tumor-associated chromosome rearrangement.

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Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma.

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The American journal of surgical pathology. 1998 ; 22 (5) : 576-587.

PMID 9591728

COL1A1-PDGFB fusion in a ring chromosome 4 found in a dermatofibrosarcoma protuberans.

Navarro M, Simon MP, Migeon C, Turc-Carel C, Pedeutour F

Genes, chromosomes & cancer. 1998 ; 23 (3) : 263-266.

PMID 9790508

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.

O'Brien KP, Seroussi E, Dal Cin P, Sciot R, Mandahl N, Fletcher JA, Turc-Carel C, Dumanski JP

Genes, chromosomes & cancer. 1998 ; 23 (2) : 187-193.

PMID 9739023

The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB.

Shimizu A, O'Brien KP, Sj��blom T, Pietras K, Buchdunger E, Collins VP, Heldin CH, Dumanski JP, Ostman A

Cancer research. 1999 ; 59 (15) : 3719-3723.

PMID 10446987

Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans by reverse transcription-polymerase chain reaction using archival formalin-fixed, paraffin-embedded tissues.

Wang J, Hisaoka M, Shimajiri S, Morimitsu Y, Hashimoto H

Diagnostic molecular pathology : the American journal of surgical pathology, part B. 1999 ; 8 (3) : 113-119.

PMID 10565681

Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis.

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Genes, chromosomes & cancer. 2001 ; 30 (3) : 305-309.

PMID 11170290

Structural and functional analysis of a chimeric protein COL1A1-PDGFB generated by the translocation t(17;22)(q22;q13.1) in Dermatofibrosarcoma protuberans (DP).

Simon MP, Navarro M, Roux D, Pouyss��gur J

Oncogene. 2001 ; 20 (23) : 2965-2975.

PMID 11420709

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Contributor(s)

Written	02-2001	Marie-Pierre Simon, Georges Maire, Florence Pedeutour

Citation

This paper should be referenced as such :

Simon MP, Maire G, Pedeutour F . PDGFB. Atlas Genet Cytogenet Oncol Haematol. February 2001 . URL : http://AtlasGeneticsOncology.org/Genes/PDGFBID155.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Jul 14 17:48:21 2008