Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Multisite phosphorylation is a common form of posttranslational protein regulation which has been used to increase the switchlike behavior of the protein response to increasing kinase concentrations. In this letter, we show that the switchlike response of multisite phosphoproteins is strongly enhanced by nonessential phosphorylation sites, a mechanism that is robust to parameter changes and easily implemented in nature. We obtained analytic estimates for the Hill exponent (or coefficient) of the switchlike response, and we observed that a tradeoff exists between the switch and the kinase threshold for activation. This also suggests a possible evolutionary mechanism for the relatively large numbers of phosphorylation sites found in various proteins.
Angeli,
Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems.
2004, Pubmed
Angeli,
Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems.
2004,
Pubmed
Brown,
Evolutionary rate heterogeneity in proteins with long disordered regions.
2002,
Pubmed
Deshaies,
Multisite phosphorylation and the countdown to S phase.
2001,
Pubmed
Furdui,
Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction.
2006,
Pubmed
Gunawardena,
Multisite protein phosphorylation makes a good threshold but can be a poor switch.
2005,
Pubmed
Iakoucheva,
The importance of intrinsic disorder for protein phosphorylation.
2004,
Pubmed
Kapuy,
Bistability by multiple phosphorylation of regulatory proteins.
2009,
Pubmed
Kawaguchi,
Thermal activation of single kinesin molecules with temperature pulse microscopy.
2001,
Pubmed
Kim,
Multisite M-phase phosphorylation of Xenopus Wee1A.
2005,
Pubmed
,
Xenbase
Lenz,
An entropic mechanism to generate highly cooperative and specific binding from protein phosphorylations.
2006,
Pubmed
Liu,
A combination of multisite phosphorylation and substrate sequestration produces switchlike responses.
2010,
Pubmed
Nash,
Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication.
2001,
Pubmed
Orlicky,
Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase.
2003,
Pubmed
Qian,
Temporal cooperativity and sensitivity amplification in biological signal transduction.
2008,
Pubmed
Serber,
Tuning bulk electrostatics to regulate protein function.
2007,
Pubmed
Strickfaden,
A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway.
2007,
Pubmed
Welcker,
Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation.
2003,
Pubmed
