Versatile regulation of multisite protein phosphorylation by the order of phosphate processing and protein–protein interactions.
In: FEBS Journal, Jg. 274 (2007-02-15), Heft 4, S. 1046-1061
Online
academicJournal
Zugriff:
Multisite protein phosphorylation is a common regulatory mechanism in cell signaling, and dramatically increases the possibilities for protein–protein interactions, conformational regulation, and phosphorylation pathways. However, there is at present no comprehensive picture of how these factors shape the response of a protein's phosphorylation state to changes in kinase and phosphatase activities. Here we provide a mathematical theory for the regulation of multisite protein phosphorylation based on the mechanistic description of elementary binding and catalytic steps. Explicit solutions for the steady-state response curves and characteristic (de)phosphorylation times have been obtained in special cases. The order of phosphate processing and the characteristics of protein–protein interactions turn out to be of overriding importance for both sensitivity and speed of response. Random phosphate processing gives rise to shallow response curves, favoring intermediate phosphorylation states of the target, and rapid kinetics. Sequential processing is characterized by steeper response curves and slower kinetics. We show systematically how qualitative differences in target phosphorylation − including graded, switch-like and bistable responses − are determined by the relative concentrations of enzyme and target as well as the enzyme–target affinities. In addition to collective effects of several phosphorylation sites, our analysis predicts that distinct phosphorylation patterns can be finely tuned by a single kinase. Taken together, this study suggests a versatile regulation of protein activation by the combined effect of structural, kinetic and thermodynamic aspects of multisite phosphorylation. [ABSTRACT FROM AUTHOR]
Copyright of FEBS Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Titel: |
Versatile regulation of multisite protein phosphorylation by the order of phosphate processing and protein–protein interactions.
|
---|---|
Autor/in / Beteiligte Person: | Salazar, Carlos ; Höfer, Thomas |
Link: | |
Zeitschrift: | FEBS Journal, Jg. 274 (2007-02-15), Heft 4, S. 1046-1061 |
Veröffentlichung: | 2007 |
Medientyp: | academicJournal |
ISSN: | 1742-464X (print) |
DOI: | 10.1111/j.1742-4658.2007.05653.x |
Schlagwort: |
|
Sonstiges: |
|