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.