Robust global sensitivity in multiple enzyme cascade system explains how the downstream cascade structure may remain unaffected by cross‐talk

FEBS Letters

Edwards, Jeremy S.²  Venkatesh, K.V.¹  Mutalik, Vivek K.¹  Singh, Aditya P.² 

[1] Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai-400076, India;Department of Chemical Engineering, University of Delaware, Newark, DE 19716, USA

关键词: Signal amplification;    Ultrasensitivity;    Robustness;    Mitogen-activated protein kinase;    Enzyme cascade;    Cross-talk;    Signal transduction;    MAPK;    mitogen-activated protein kinase;    MAPKK;    MAP kinase kinase;    MAPKKK;    MAP kinase kinase kinase;    MAPKKKK;    MAP kinase kinase kinase kinase;   

DOI  :  10.1016/S0014-5793(04)00021-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A steady-state framework was applied to the ubiquitous tricyclic enzyme cascade structure, as seen in the mitogen-activated protein (MAP) kinase system, to analyze the effect of upstream kinase concentrations on final output response. The results suggest that signal amplification achieved by the cascade structure ensured that the modifying enzymes at various steps of the cascade were nearly saturated. Thus, there was no change in the response sensitivity with increasing upstream kinase concentration. Analysis was also extended to branching of a signaling pathway as an example of cross-talk. It was observed that the cascade structure confers a larger share of the signal transduction properties to its last kinase. This phenomenon in enzyme cascades may explain how the response of the terminal MAP kinase is unaffected by cross-talk of upstream kinases.

【 授权许可】

Unknown