A kinase-inactive type II TGFbeta receptor impairs BMP signaling in human breast cancer cells.
Dominant negative receptor mutants are often utilized in order to abrogate signaling induced by growth factors. We have previously shown that expression of a dominant negative type II TGFbeta receptor (dnTbetaRII) in MDA-MB-231 breast cancer cells effectively abrogates TGFbeta signaling. In this letter, we report that expression of dnTbetaRII also impairs BMP2-mediated Smad1 phosphorylation as well as BMP2-mediated Smad-dependent transcriptional responses, resulting in an attenuation of BMP-mediated anti-proliferative effects. The fact that dnTbetaRII not only abrogates TGFbeta signaling but BMP signaling as well has important implications for the interpretation of data in which dominant negative mutants are utilized.
Dumont
Nancy
N
Department of Cancer Biology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232-6307, USA.
Arteaga
Carlos L
CL
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C497399:SMAD1 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II