Distinct pathways regulate transforming growth factor beta 1-stimulated proto-oncogene and extracellular matrix gene expression.
The effect of pertussis toxin (PT) on transforming growth factor beta 1 (TGF beta 1)-induced proto-oncogene expression was investigated in AKR-2B fibroblasts. PT substantially abolished c-sis and c-myc mRNA expression following TGF beta 1 stimulation. This inhibitory effect was specific for TGF beta 1-stimulated proto-oncogene expression and associated with the ADP-ribosylation of a 41-kDa substrate. Actinomycin D decay and nuclear run-on experiments demonstrated that the inhibitory effects of PT are a result of decreased transcriptional activation and not to an increased decay of proto-oncogene message. PT did not, however, affect TGF beta 1-stimulated fibronectin and collagen mRNA accumulation nor did it have any inhibitory effect on TGF beta 1-induced morphological transformation. These data indicate that TGF beta 1-stimulated gene expression is coupled to multiple pathways distinguished by their sensitivity to PT.
Howe
P H
PH
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Cunningham
M R
MR
Leof
E B
EB
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D037342:Pertussis Toxin; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D020574:Proto-Oncogene Proteins c-sis; D011519:Proto-Oncogenes / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D005353:Fibronectins; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D010566:Virulence Factors, Bordetella; D000244:Adenosine Diphosphate; D015291:Transforming Growth Factors; D003094:Collagen; D037342:Pertussis Toxin