Journal
FEBS JOURNAL
Volume 276, Issue 12, Pages 3177-3198Publisher
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1742-4658.2009.07027.x
Keywords
enzyme processivity; kinetic proofreading; mathematical models; order of phospho-site processing; ultrasensitivity
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Funding
- Helmholtz Association
- German Federal Ministry for Education and Research (BMBF)
- EU-FP7 Network Systems Biology of T-cell Activation (SYBILLA)
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Multisite phosphorylation is an important mechanism for fine-tuned regulation of protein function. Mathematical models developed over recent years have contributed to elucidation of the functional consequences of a variety of molecular mechanisms involved in processing of the phosphorylation sites. Here we review the results of such models, together with salient experimental findings on multisite protein phosphorylation. We discuss how molecular mechanisms that can be distinguished with respect to the order and processivity of phosphorylation, as well as other factors, regulate changes in the sensitivity and kinetics of the response, the synchronization of molecular events, signalling specificity, and other functional implications.
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