A Novel Regulatory Mechanism of the Bone Morphogenetic Protein (Bmp) Signaling Pathway Involving the Carboxyl-terminal Tail Domain of Bmp Type Ii Receptor.
From: Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Molecular and cellular biology
- Publish Date: Aug 2007
- ISSN: 0270-7306
- Volume: 27
- Issue: 16
- Pages: 5776-89
- Medium: Print
- Language: English
- Citation (JAMA): Chan Mun Chun, Nguyen Peter H, Davis Brandi N, et al. A Novel Regulatory Mechanism of the Bone Morphogenetic Protein (Bmp) Signaling Pathway Involving the Carboxyl-terminal Tail Domain of Bmp Type Ii Receptor.. Mol. Cell. Biol. Aug 2007;27:5776-89
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.
Mesh Headings (Keywords): Animals, Bone Morphogenetic Protein Receptors, Type II, Bone Morphogenetic Proteins, COS Cells, Cell Cycle Proteins, Cercopithecus aethiops, Down-Regulation, Humans, Mice, Myocytes, Smooth Muscle, NIH 3T3 Cells, Protein Binding, Protein Processing, Post-Translational, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Pulmonary Artery, Repressor Proteins, Signal Transduction, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases
Check for Full Text / PubMed Unique Identifier (PMID): 17576816
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.