A dominant-negative receptor for type beta transforming growth factors created by deletion of the kinase domain.
To prove the postulated role of type beta transforming growth factors (TGF beta) in cardiac development and other events, specific inhibitors of TGF beta signal transduction are needed. We truncated the type II TGF beta receptor cDNA (delta kT beta RII), to delete the predicted serine/threonine kinase cytoplasmic domain. delta kT beta RII was co-transfected into neonatal cardiac myocytes, together with reporter constructs for two cardiac-restricted genes that are regulated antithetically by TGF beta. delta kT beta RII impaired activation of the skeletal alpha-actin promoter by TGF beta 1, -2, and -3 and, conversely, impaired TGF beta inhibition of alpha-myosin heavy chain transcription. Thus, a kinase-defective T beta RII blocks signaling by all three mammalian TGF beta isoforms, and can disrupt both positive and negative control of transcription by TGF beta.
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
T
T
Brand
W R
WR
MacLellan
M D
MD
Schneider
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D017384:Sequence Deletion; D013489:Suppression, Genetic; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D001616:beta-Galactosidase