A novel regulatory mechanism of the bone morphogenetic protein (BMP) signaling pathway involving the carboxyl-terminal tail domain of BMP type II receptor.

@article{citeulike:2048336, abstract = {Bone morphogenetic protein (BMP) signaling regulates many different biological processes, including cell growth, differentiation, and embryogenesis. BMPs bind to heterogeneous complexes of transmembrane serine/threonine (Ser/Thr) kinase receptors known as the BMP type I and II receptors (BMPRI and BMPRII). BMPRII phosphorylates and activates the BMPRI kinase, which in turn activates the Smad proteins. The cytoplasmic region of BMPRII contains a "tail" domain (BMPRII-TD) with no enzymatic activity or known regulatory function. The discovery of mutations associated with idiopathic pulmonary artery hypertension mapping to BMPRII-TD underscores its importance. Here, we report that Tribbles-like protein 3 (Trb3) is a novel BMPRII-TD-interacting protein. Upon BMP stimulation, Trb3 dissociates from BMPRII-TD and triggers degradation of Smad ubiquitin regulatory factor 1 (Smurf1), which results in the stabilization of BMP receptor-regulated Smads and potentiation of the Smad pathway. Downregulation of Trb3 inhibits BMP-mediated cellular responses, including osteoblast differentiation of C2C12 cells and maintenance of the smooth muscle phenotype of pulmonary artery smooth muscle cells. Thus, Trb3 is a critical component of a novel mechanism for regulation of the BMP pathway by BMPRII.}, address = {Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.}, author = {Chan, M. C. and Nguyen, P. H. and Davis, B. N. and Ohoka, N. and Hayashi, H. and Du, K. and Lagna, G. and Hata, A. }, citeulike-article-id = {2048336}, doi = {http://dx.doi.org/10.1128/MCB.00218-07}, issn = {0270-7306}, journal = {Mol Cell Biol}, keywords = {bmpr2}, month = {August}, number = {16}, pages = {5776--5789}, posted-at = {2007-12-03 08:41:12}, priority = {2}, title = {A novel regulatory mechanism of the bone morphogenetic protein (BMP) signaling pathway involving the carboxyl-terminal tail domain of BMP type II receptor.}, url = {http://dx.doi.org/10.1128/MCB.00218-07}, volume = {27}, year = {2007} }

TY - JOUR ID - citeulike:2048336 L3 - citeulike-article-id:2048336 TI - A novel regulatory mechanism of the bone morphogenetic protein (BMP) signaling pathway involving the carboxyl-terminal tail domain of BMP type II receptor. JF - Mol Cell Biol VL - 27 IS - 16 SP - 5776 EP - 5789 AD - Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. SN - 0270-7306 N2 - Bone morphogenetic protein (BMP) signaling regulates many different biological processes, including cell growth, differentiation, and embryogenesis. BMPs bind to heterogeneous complexes of transmembrane serine/threonine (Ser/Thr) kinase receptors known as the BMP type I and II receptors (BMPRI and BMPRII). BMPRII phosphorylates and activates the BMPRI kinase, which in turn activates the Smad proteins. The cytoplasmic region of BMPRII contains a "tail" domain (BMPRII-TD) with no enzymatic activity or known regulatory function. The discovery of mutations associated with idiopathic pulmonary artery hypertension mapping to BMPRII-TD underscores its importance. Here, we report that Tribbles-like protein 3 (Trb3) is a novel BMPRII-TD-interacting protein. Upon BMP stimulation, Trb3 dissociates from BMPRII-TD and triggers degradation of Smad ubiquitin regulatory factor 1 (Smurf1), which results in the stabilization of BMP receptor-regulated Smads and potentiation of the Smad pathway. Downregulation of Trb3 inhibits BMP-mediated cellular responses, including osteoblast differentiation of C2C12 cells and maintenance of the smooth muscle phenotype of pulmonary artery smooth muscle cells. Thus, Trb3 is a critical component of a novel mechanism for regulation of the BMP pathway by BMPRII. KW - bmpr2 AU - Chan, MC AU - Nguyen, PH AU - Davis, BN AU - Ohoka, N AU - Hayashi, H AU - Du, K AU - Lagna, G AU - Hata, A PY - 2007/08// UR - http://dx.doi.org/10.1128/MCB.00218-07 ER -