Load-Induced Modulation of Signal Transduction Networks

被引:55
作者
Jiang, Peng [1 ]
Ventura, Alejandra C. [2 ,3 ]
Sontag, Eduardo D. [4 ]
Merajver, Sofia D. [5 ]
Ninfa, Alexander J. [1 ]
Del Vecchio, Domitilla [6 ]
机构
[1] Univ Michigan, Dept Biol Chem, Sch Med, Ann Arbor, MI 48109 USA
[2] Univ Buenos Aires, Inst Physiol Mol Biol & Neurosci, Dept Biol, Buenos Aires, DF, Argentina
[3] Univ Michigan, Lab Fisiol & Biol Mol, Dept Fisiol Biol Mol & Celular, IFIBYNE CONICET,Fac Ciencias Exactas y Nat, Ann Arbor, MI 48109 USA
[4] Rutgers State Univ, Dept Math, New Brunswick, NJ 08854 USA
[5] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
[6] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
关键词
NITROGEN ASSIMILATION; COVALENT MODIFICATION; ULTRASENSITIVITY; RETROACTIVITY; SPECIFICITY; DEPENDENCE; COMPROMISE;
D O I
10.1126/scisignal.2002152
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Biological signal transduction networks are commonly viewed as circuits that pass along information-in the process amplifying signals, enhancing sensitivity, or performing other signal-processing tasks-to transcriptional and other components. Here, we report on a "reverse-causality" phenomenon, which we call load-induced modulation. Through a combination of analytical and experimental tools, we discovered that signaling was modulated, in a surprising way, by downstream targets that receive the signal and, in doing so, apply what in physics is called a load. Specifically, we found that non-intuitive changes in response dynamics occurred for a covalent modification cycle when load was present. Loading altered the response time of a system, depending on whether the activity of one of the enzymes was maximal and the other was operating at its minimal rate or whether both enzymes were operating at submaximal rates. These two conditions, which we call "limit regime" and "intermediate regime," were associated with increased or decreased response times, respectively. The bandwidth, the range of frequency in which the system can process information, decreased in the presence of load, suggesting that downstream targets participate in establishing a balance between noise-filtering capabilities and a circuit's ability to process high-frequency stimulation. Nodes in a signaling network are not independent relay devices, but rather are modulated by their downstream targets.
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页数:10
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