TAILIEUCHUNG - Báo cáo khoa học: Bistability from double phosphorylation in signal transduction Kinetic and structural requirements

Previous studies have suggested that positive feedback loops and ultrasensi-tivity are prerequisites for bistability in covalent modification cascades. However, it was recently shown that bistability and hysteresis can also arise solely from multisite phosphorylation. | ỊFEBS Journal Bistability from double phosphorylation in signal transduction Kinetic and structural requirements Fernando Ortega1 2 3 Jose L. Garces1 2 Francesc Mas1 2 Boris N. Kholodenko4 and Marta Cascante1 3 1 Centre for Research in TheoreticalChemistry Scientific Park of Barcelona Spain 2 PhysicalChemistry Department University of Barcelona Spain 3 Department of Biochemistry and Molecular Biology University of Barcelona Spain 4 Department of Pathology Anatomy and CellBiology Thomas Jefferson University Philadelphia PA USA Keywords bistability metabolic cascades signaling networks ultrasensitivity Correspondence M. Cascante Department of Biochemistry and Molecular Biology University of Barcelona and Centre for Research in TheoreticalChemistry Scientific Park of Barcelona Marti i Franques 1 08028 Barcelona Spain Fax 34 93 402 12 19 Tel 34 93 402 15 93 E-mail martacascante@ Note The mathematical model described here has been submitted to the Online Cellular Systems Modelling Database and can be accessed free of charge at http . database Ortega Received 19 February 2006 revised 13 June 2006 accepted 23 June 2006 doi Previous studies have suggested that positive feedback loops and ultrasensitivity are prerequisites for bistability in covalent modification cascades. However it was recently shown that bistability and hysteresis can also arise solely from multisite phosphorylation. Here we analytically demonstrate that double phosphorylation of a protein or other covalent modification generates bistability only if a the two phosphorylation or the two dephosphorylation reactions are catalyzed by the same enzyme b the kinetics operate at least partly in the zero-order region and c the ratio of the catalytic constants of the phosphorylation and dephosphorylation steps in the first modification cycle is less than this ratio in the second cycle. We also show that multisite phosphorylation enlarges the .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• Crystal structure
• medical analysis
• biochemical studies
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• environmental medicine