Chromosomal location, exon structure, and vascular expression patterns of the human PDGFC and PDGFD genes.
BACKGROUND
Platelet-derived growth factor (PDGF), which is a major mitogen for vascular smooth muscle cells and has been implicated in the pathogenesis of arteriosclerosis, is composed of dimers of PDGF-A and PDGF-B polypeptide chains, encoded by different genes. Here, we have analyzed the chromosomal localization, structure, and expression of 2 newly identified human genes of the PDGF family, called PDGFC and PDGFD.


RESULTS
We used fluorescence in situ hybridization to locate PDGFC and PDGFD in chromosomes 4q32 and 11q22.3 to 23.2, respectively. Exon structures of PDGFC and PDGFD were determined by sequencing from genomic DNA clones. The coding region of PDGFC consists of 6 and PDGFD of 7 exons, of which the last 2 encode the C-terminal PDGF cystine knot growth factor homology domain. An N-terminal CUB domain is encoded by exons 2 and 3 of both genes, and a region of proteolytic cleavage involved in releasing and activating the growth factor domain is located in exon 4 in PDGFC and exon 5 in PDGFD. PDGF-C was expressed predominantly in smooth muscle cells and PDGF-D in fibroblastic adventitial cells, and both genes were active in cultured endothelial cells and in a variety of tumor cell lines. Both PDGF-C and PDGF-D also stimulated human coronary artery smooth muscle cells.


CONCLUSIONS
PDGFC and PDGFD have similar genomic structures, which resemble those of the PDGFA and PDGFB genes. Their expression in the arterial wall and cultured vascular cells suggests that they can transduce proliferation/migration signals to pericytes and smooth muscle cells.
Uutela
M
M
Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Biomedicum Helsinki, Finland.
Laurén
J
J
Bergsten
E
E
Li
X
X
Horelli-Kuitunen
N
N
Eriksson
U
U
Alitalo
K
K
D020816:Amino Acid Motifs; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D017124:Conserved Sequence; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D008222:Lymphokines; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D020161:Physical Chromosome Mapping; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012077:Renal Artery / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D008222:Lymphokines; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; C411423:platelet-derived growth factor C