tailieunhanh - Báo cáo khoa học: Multisite protein phosphorylation – from molecular mechanisms to kinetic models

Multisite phosphorylation is an important mechanism for fine-tuned regula-tion 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. | ỊFEBS Journal REVIEW ARTICLE Multisite protein phosphorylation - from molecular mechanisms to kinetic models Carlos Salazar and Thomas Heifer Research Group Modeling of BiologicalSystems B086 German Cancer Research Center DKFZ Im Neuenheimer Feld 280 Heidelberg Germany Keywords enzyme processivity kinetic proofreading mathematicalmodels order of phospho-site processing ultrasensitivity Correspondence C. Salazar Research Group Modeling of BiologicalSystems B086 German Cancer Research Center DKFZ Im Neuenheimer Feld 280 69120 Heidelberg Germany Fax 49 6221 54 51487 Tel 49 6221 54 51383 E-mail T. Hofer Research Group Modeling of BiologicalSystems B086 German Cancer Research Center DKFZ Im Neuenheimer Feld 280 69120 Heidelberg Germany Fax 49 6221 54 51487 Tel 49 6221 54 51380 E-mail Received 15 January 2009 revised 4 March 2009 accepted 27 March 2009 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. doi Introduction Signal transduction networks are formed in large part by interacting protein kinases and phosphatases. Phosphorylation of proteins by kinases or dephosphorylation by phosphatases provides docking sites for interaction partners or triggers conformational changes that alter a protein s enzymatic .