Combinatorial Signal Perception in the BMP Pathway
| Autor: | Yaron E. Antebi, Mengsha Gong, Michael B. Elowitz, Christina Su, Bogdan Bintu, Reed D. McCardell, James M. Linton, Heidi Klumpe |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
SMAD Computational biology Biology Ligands Bone morphogenetic protein Models Biological Article General Biochemistry Genetics and Molecular Biology Cell Line Feedback Mice 03 medical and health sciences Signal perception Redundancy (engineering) Animals Receptor Embryonic Stem Cells Genetics Flexibility (engineering) Flow Cytometry 030104 developmental biology Bone Morphogenetic Proteins NIH 3T3 Cells Bmp pathway Signal transduction Signal Transduction |
| Zdroj: | Cell. 170:1184-1196.e24 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2017.08.015 |
| Popis: | The Bone Morphogenetic Protein (BMP) signaling pathway comprises multiple ligands and receptors that interact promiscuously with one another, and typically appear in combinations. This feature is often explained in terms of redundancy and regulatory flexibility, but it has remained unclear what signal processing capabilities it provides. Here, we show that the BMP pathway processes multi-ligand inputs using a specific repertoire of computations, including ratiometric sensing, balance detection and imbalance detection. These computations operate on the relative levels of different ligands, and can arise directly from competitive receptor-ligand interactions. Furthermore, cells can select different computations to perform on the same ligand combination through expression of alternative sets of receptor variants. These results provide a direct signal processing role for promiscuous receptor-ligand interactions, and establish operational principles for quantitatively controlling cells with BMP ligands. Similar principles could apply to other promiscuous signaling pathways. |
| Databáze: | OpenAIRE |
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