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bioRxiv · 10.1101/2023.07.10.548398

Liebig's law of the minimum in the TGF-β pathway

Li, Y.·Deng, D.·Höfer, C. T.·Kim, J.·Heo, W. D.·Xu, Q.·Liu, X.·Zi, Z.
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Abstract

Cells use signaling pathways to sense and respond to their environments. The transforming growth factor-{beta} (TGF-{beta}) pathway produces context-specific responses. Here, we combined modeling and experimental analysis to study the dependence of the output of the TGF-{beta} pathway on the abundance of signaling molecules in the pathway. We showed that the TGF-{beta} pathway processes the variation of TGF-{beta} receptor abundance using Liebigs law of the minimum, meaning that the output-modifying factor is the signaling protein that is most limited, to determine signaling responses across cell types and in single cells. We found that the abundance of either the type I (TGFBR1) or type II (TGFBR2) TGF-{beta} receptor determined the responses of cancer cell lines, such that the receptor with relatively low abundance dictates the response. Furthermore, nuclear SMAD2 signaling correlated with the abundance of TGF-{beta} receptor in single cells depending on the relative expression levels of TGFBR1 and TGFBR2. A similar control principle could govern the heterogeneity of signaling responses in other signaling pathways. One-sentence summaryHeterogeneous TGF-{beta} signaling responses are dictated by the low abundance TGF-{beta} receptor in different cell types and in single cells, resembling Liebigs law of the minimum.

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Li, Y., Deng, D., Höfer, C. T., Kim, J., Heo, W. D., Xu, Q., Liu, X., Zi, Z.. 2023-07-14. Liebig's law of the minimum in the TGF-β pathway. https://doi.org/10.1101/2023.07.10.548398

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