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 5.067
Resource
Human and Animal Cells ATDC5(RCB0565)