The induction of early response genes in rat smooth muscle cells by PDGF-AA is not sufficient to stimulate DNA-synthesis.
The effect of the three platelet-derived growth factor (PDGF) isoforms AA, AB and BB on the induction of the early growth response genes c-fos, egr-1 and c-myc mRNA in vascular smooth muscle cells from rat was compared with their respective mitogenic potency. The three PDGF isoforms strongly stimulated the induction to a similar extent. In contrast, PDGF-AB and -BB provoked a marked DNA synthesis whereas PDGF-AA exerted only a poor mitogenic effect in smooth muscle cells. PDGF-AA-stimulated receptor autophosphorylation was not detectable in comparison with the strong effect elicited by PDGF-AB or -BB and correlated with its low mitogenicity but not with the almost equal induction of the early response genes. It is discussed that no or only very low receptor phosphorylation is required to link receptor activation to the induction of c-fos, egr-1 or c-myc. Furthermore the induction of the investigated gene does not seem to be sufficient for an optimal mitogenic response.
Sachinidis
A
A
Medizinische Universitäts-Poliklinik, Bonn, Germany.
Schulte
K
K
Ko
Y
Y
Meyer zu Brickwedde
M K
MK
Hoppe
V
V
Hoppe
J
J
Vetter
H
H
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos; D016259:Genes, myc; D017874:Immediate-Early Proteins; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D014157:Transcription Factors; D019000:Phosphotyrosine; D014443:Tyrosine; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor