Multistep phosphorylation systems: tunable components of biological signaling circuits

Multisite phosphorylation of proteins is a powerful signal processing mechanism that plays crucial roles in cell division and differentiation as well as in disease. We recently demonstrated a novel phenomenon in cell cycle regulation by showing that cyclin-dependent kinase-dependent multisite phosph...

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Bibliographic Details
Published in:Molecular biology of the cell 2014-11, Vol.25 (22), p.3456-3460
Main Authors: Valk, Evin, Venta, Rainis, Ord, Mihkel, Faustova, Ilona, Kõivomägi, Mardo, Loog, Mart
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Cell Differentiation
Cell Division
Cyclin-Dependent Kinases - genetics
Cyclin-Dependent Kinases - metabolism
Gene Expression Regulation, Fungal
Molecular Sequence Data
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphorylation
Protein Processing, Post-Translational
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Signal Transduction
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Summary:Multisite phosphorylation of proteins is a powerful signal processing mechanism that plays crucial roles in cell division and differentiation as well as in disease. We recently demonstrated a novel phenomenon in cell cycle regulation by showing that cyclin-dependent kinase-dependent multisite phosphorylation of a crucial substrate is performed sequentially in the N-to-C terminal direction along the disordered protein. The process is controlled by key parameters, including the distance between phosphorylation sites, the distribution of serines and threonines in sites, and the position of docking motifs. According to our model, linear patterns of phosphorylation along disordered protein segments determine the signal-response function of a multisite phosphorylation switch. Here we discuss the general advantages and engineering principles of multisite phosphorylation networks as processors of kinase signals. We also address the idea of using the mechanistic logic of linear multisite phosphorylation networks to design circuits for synthetic biology applications.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E14-02-0774