| RRC ID |
61198
|
| Author |
Sengle G, Ono RN, Lyons KM, Bächinger HP, Sakai LY.
|
| Title |
A new model for growth factor activation: type II receptors compete with the prodomain for BMP-7.
|
| Journal |
J Mol Biol
|
| Abstract |
Bone morphogenetic proteins (BMPs) are morphogens with long-range signaling activities. BMP-7 is secreted as a stable complex consisting of a growth factor noncovalently associated with two propeptides. In other transforming growth factor-beta-like growth factor complexes, the prodomain (pd) confers latency to the complex. However, we detected no difference in signaling capabilities between the growth factor and the BMP-7 complex in multiple in vitro bioactivity assays. Biochemical and biophysical methods elucidated the interaction between the BMP-7 complex and the extracellular domains of its type I and type II receptors. Results showed that type II receptors, such as BMP receptor II, activin receptor IIA, and activin receptor IIB, competed with the pd for binding to the growth factor and displaced the pd from the complex. In contrast, type I receptors interacted with the complex without displacing the pd. These studies suggest a new model for growth factor activation in which proteases or other extracellular molecules are not required and provide a molecular mechanism consistent with a role for BMP receptors in the establishment of early morphogen gradients.
|
| Volume |
381(4)
|
| Pages |
1025-39
|
| Published |
2008-9-12
|
| DOI |
10.1016/j.jmb.2008.06.074
|
| PII |
S0022-2836(08)00801-2
|
| PMID |
18621057
|
| PMC |
PMC2705212
|
| MeSH |
Activin Receptors, Type II / metabolism
Animals
Binding Sites
Binding, Competitive
Bone Morphogenetic Protein 7
Bone Morphogenetic Protein Receptors, Type I / metabolism
Bone Morphogenetic Protein Receptors, Type II / metabolism*
Bone Morphogenetic Proteins / chemistry*
Bone Morphogenetic Proteins / metabolism*
Cell Line
Dimerization
Humans
Intercellular Signaling Peptides and Proteins / metabolism*
Mice
Models, Biological*
Molecular Weight
Myostatin
Protein Binding
Protein Structure, Tertiary
Surface Plasmon Resonance
Transforming Growth Factor beta / chemistry*
Transforming Growth Factor beta / metabolism*
Ultracentrifugation
|
| IF |
4.76
|
| Resource |
| Human and Animal Cells |
ATDC5(RCB0565) |
