A novel murine PDGF-D splicing variant results in significant differences in peptide expression and function.
Platelet-derived growth factor (PDGF) is a potent mesenchymal cell mitogen and chemoattractant involved in the pathogenesis of fibroproliferative diseases. There are four known PDGF ligand isoforms designated A-D, two of which, C and D, were only recently discovered. We have identified a splicing variant in the PDGF-D isoform that occurs in mice, but not in humans. The presence of the splicing variant in murine PDGF-D appears to be due to an aberration in the splicing site at the junction of exons 5 and 6. The splicing variant results in a deletion predicted to have significant effects on peptide activity since it results in the deletion of bases within the cysteine knot domain that are important for peptide dimerization and receptor binding. It is important to appreciate differences between murine and human PDGF gene expression because PDGF is a key mitogen in the pathogenesis of fibrosis and mice are commonly employed as models for human disease.
Zhuo
Ying
Y
Tulane University Health Sciences Center, Departments of Medicine and Pathology, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
Hoyle
Gary W
GW
Zhang
Jian
J
Morris
Gilbert
G
Lasky
Joseph A
JA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D008222:Lymphokines; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D008222:Lymphokines; C427493:PDGFD protein, human; C498951:Pdgfd protein, mouse; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger