title: Turnover of protein phosphorylation evolving under stabilizing selection.
abstract: Most proteins are regulated by posttranslational modifications and changes in these modifications contribute to evolutionary changes as well as to human diseases. Phosphorylation of serines, threonines, and tyrosines are the most common modifications identified to date in eukaryotic proteomes. While the mode of action and the function of most phosphorylation sites remain unknown, functional studies have shown that phosphorylation affects protein stability, localization and ability to interact. Two broad modes of action have been described for protein phosphorylation. The first mode corresponds to the canonical and qualitative view whereby single phosphorylation sites act as molecular switches that either turn on or off specific protein functions through direct or allosteric effects. The second mode is more akin to a rheostat than a switch. In this case, a group of phosphorylation sites in a given protein region contributes collectively to the modification of the protein, irrespective of the precise position of individual sites, through an aggregate property. Here we discuss these two types of regulation and examine how they affect the rate and patterns of protein phosphorylation evolution. We describe how the evolution of clusters of phosphorylation sites can be studied under the framework of complex traits evolution and stabilizing selection.
authors.affiliation: Département de Biologie, Université Laval Québec, QC, Canada ; Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval Québec, QC, Canada ; Network for Research on Protein Function, Structure, and Engineering (PROTEO), Univeristé Laval Québec, QC, Canada.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Landry
authors.affiliation: Département de Biologie, Université Laval Québec, QC, Canada ; Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval Québec, QC, Canada ; Network for Research on Protein Function, Structure, and Engineering (PROTEO), Univeristé Laval Québec, QC, Canada.
authors.forename: Luca
authors.initials: L
authors.lastname: Freschi
authors.affiliation: Department of Cell and Systems Biology, University of Toronto Toronto, ON, Canada.
authors.forename: Taraneh
authors.initials: T
authors.lastname: Zarin
authors.affiliation: Department of Cell and Systems Biology, University of Toronto Toronto, ON, Canada ; Department of Ecology and Evolutionary Biology, University of Toronto Toronto, ON, Canada ; Center for Analysis of Genome Evolution and Function, University of Toronto Toronto, ON, Canada.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Moses
keywords: cell signaling; evolutionary turnover; molecular evolution; molecular rheostats; molecular switches; protein evolution; protein phosphorylation
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