Signaling pathways as linear transmitters

ELife
Harry Nunns, Lea Goentoro

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, MAPK/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.

References

Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·C Y Huang, J E Ferrell
Jul 25, 1997·The Journal of Biological Chemistry·J E Ferrell, R R Bhatt
Jan 2, 2003·Nature Reviews. Genetics·André Pires-daSilva, Ralf J Sommer
Mar 22, 2003·Experimental Cell Research·Ami CitriYosef Yarden
Jan 21, 2004·Molecular Cell·Keiko TamaiXi He
Mar 3, 2004·Nature Reviews. Molecular Cell Biology·Lan Xu, Joan Massagué
Jul 29, 2004·Journal of Cell Science·Francisco J NicolásCaroline S Hill
Jan 25, 2005·Molecular Cell·Michele K DoughertyDeborah K Morrison
May 19, 2005·Molecular and Cellular Biology·Jeffrey P MackeiganJohn Blenis
Aug 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Marie-Claire DelfiniOlivier Pourquié
Oct 18, 2005·Nature Reviews. Molecular Cell Biology·Walter Kolch
Dec 3, 2005·Genes & Development·Joan MassaguéDavid Wotton
Feb 21, 2007·Nature Cell Biology·Silvia D M SantosPhilippe I H Bastiaens
Dec 25, 2007·Nature Cell Biology·Alexander AulehlaOlivier Pourquié
Apr 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Bernhard SchmiererCaroline S Hill
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Dmitry NevozhayGábor Balázsi
Jun 12, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Catherine ItmanKate L Loveland
Jul 22, 2009·Developmental Cell·Bryan T MacDonaldXi He
Nov 18, 2009·Molecular Cell·Sheng GaoJoan Massagué
Dec 17, 2009·Molecular Cell·Lea Goentoro, Marc W Kirschner
Dec 17, 2009·Molecular Cell·Cellina Cohen-SaidonUri Alon
Dec 24, 2010·Science Signaling·Oliver E SturmWalter Kolch
Jan 18, 2011·Integrative Biology : Quantitative Biosciences From Nano to Macro·Vinicio González-PérezRichard P Sear
Jan 22, 2011·Nature Reviews. Molecular Cell Biology·Roi Avraham, Yosef Yarden
May 27, 2011·Molecular Systems Biology·Raphaela Fritsche-GuentherNils Blüthgen
Sep 17, 2011·Science·Raymond CheongAndre Levchenko
Mar 31, 2012·PloS One·Geoffroy AndrieuxNathalie Théret
Jun 12, 2012·Cell·Hans Clevers, Roel Nusse

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Citations

Oct 26, 2018·ELife·Steven S AndrewsGábor Balázsi
Feb 5, 2021·Cell Systems·Christian Cuba Samaniego, Elisa Franco
Jun 18, 2021·Cell Systems·Nika ShakibaDomitilla Del Vecchio
Jul 9, 2021·Nature Communications·Karol NienałtowskiMichał Komorowski

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