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The discovery of modular binding domains: building blocks of cell signalling


Cell signalling — the ability of a cell to process information from the environment and change its behaviour in response — is a central property of life. Signalling depends on proteins that are assembled from a toolkit of modular domains, each of which confers a specific activity or function. The discovery of modular protein- and lipid-binding domains was a crucial turning point in understanding the logic and evolution of signalling mechanisms.

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Figure 1: Modular domains timeline.
Figure 2: GRB2 mediates receptor Tyr kinase (RTK)-induced RAS activation.
Figure 3: Enzyme regulation by modular binding domains.


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Many, many investigators were involved in the discoveries described in this article, and I sincerely apologize to those whose work was not explicitly mentioned or cited. For the sake of narrative clarity, I chose to focus on a few specific examples, but it was not my intent to minimize the many important contributions made by others. I am very grateful to Tony Hunter and Mike Yaffe for critically reading this manuscript, Michele Tinti and Gianni Cesareni for providing figures, and Kalle Saksela and Marius Sudol for helpful discussions. The author was supported by grant U01 CA154966 from the US National Institutes of Health.

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Correspondence to Bruce J. Mayer.

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Mayer, B. The discovery of modular binding domains: building blocks of cell signalling. Nat Rev Mol Cell Biol 16, 691–698 (2015).

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