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.

中文翻译：

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BMP通路中的组合信号感知。

骨形态发生蛋白（BMP）信号传导途径包含多个配体和受体，它们彼此混杂地相互作用，并且通常以组合形式出现。通常以冗余和法规灵活性来解释此功能，但仍不清楚它提供什么信号处理功能。在这里，我们展示了BMP途径使用特定的计算库来处理多配体输入，包括比率传感，平衡检测和不平衡检测。这些计算在不同配体的相对水平上进行，并且可以直接从竞争性受体-配体相互作用中产生。此外，细胞可以通过表达不同的受体变体集来选择不同的计算以对相同的配体组合进行操作。这些结果为混杂的受体-配体相互作用提供了直接的信号处理作用，并建立了用BMP配体定量控制细胞的操作原理。类似的原理可以适用于其他混杂信号通路。