Signaling pathways as linear transmitters

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Abstract

One challenge in biology is to make sense of the complexity of biological networks. A good system to approach this is signaling pathways, whose well-characterized molecular details allow us to relate the internal processes of each pathway to their input-output behavior. In this study, we analyzed mathematical models of three metazoan signaling pathways: the canonical Wnt, ERK, and Tgfβ pathways. We find an unexpected convergence: the three pathways behave in some physiological contexts as linear signal transmitters. Testing the results experimentally, we present direct measurements of linear input-output behavior in the Wnt and ERK pathways. Analytics from each model further reveal that linearity arises through different means in each pathway, which we tested experimentally in the Wnt and ERK pathways. Linearity is a desired property in engineering where it facilitates fidelity and superposition in signal transmission. Our findings illustrate how cells tune different complex networks to converge on the same behavior.

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All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2 and 3.

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Harry Nunns

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States

For correspondence
hnunns@caltech.edu

Competing interests
The authors declare that no competing interests exist.
Lea Goentoro

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States

For correspondence
goentoro@caltech.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3904-0195

Funding

James S. McDonnell Foundation (220020365)

Lea Goentoro

National Science Foundation (NSF.145863)

Lea Goentoro

National Institutes of Health (5T32GM007616-37)

Harry Nunns

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.