Apart from flexibility, robustness is a second general
property of signalling pathways that is not readily
apparent. Both theoretical and experimental data postulate
that two types of general network architecture
might account for robustness: positive- and negativefeedback
loops24. In positive-feedback loops, the formation
of the ligand is often enhanced, thereby amplifying,
stabilizing or prolonging signalling. The enhancement
of signalling pathways by positive feedback can guarantee
the commitment of a cell to a particular developmental
decision25. Positive-feedback regulation is used
in developmental contexts, such as the maintenance of
Ultrabithorax (Ubx) expression in the Drosophila gut by
Tgf-β and Wnt signalling, but is also seen in aberrant
circumstances, such as the autocrine stimulation in
tumour cells26,27. Negative-feedback loops are used to
inhibit and/or limit signalling. One example is the limitation
of Hh signalling to the posterior compartment
of the Drosophila wing disc; anterior cells that receive
Hh ligand activate transcription of Patched, a membrane
protein that sequesters Hh, thereby preventing its
diffusion28. By using artificial gene networks, it has been
shown that negative-feedback loops also have the property
to stabilize fluctuations of biochemical
parameters29
Apart from flexibility, robustness is a second generalproperty of signalling pathways that is not readilyapparent. Both theoretical and experimental data postulatethat two types of general network architecturemight account for robustness: positive- and negativefeedbackloops24. In positive-feedback loops, the formationof the ligand is often enhanced, thereby amplifying,stabilizing or prolonging signalling. The enhancementof signalling pathways by positive feedback can guaranteethe commitment of a cell to a particular developmentaldecision25. Positive-feedback regulation is usedin developmental contexts, such as the maintenance ofUltrabithorax (Ubx) expression in the Drosophila gut byTgf-β and Wnt signalling, but is also seen in aberrantcircumstances, such as the autocrine stimulation intumour cells26,27. Negative-feedback loops are used toinhibit and/or limit signalling. One example is the limitationof Hh signalling to the posterior compartmentof the Drosophila wing disc; anterior cells that receiveHh ligand activate transcription of Patched, a membraneprotein that sequesters Hh, thereby preventing itsdiffusion28. By using artificial gene networks, it has beenshown that negative-feedback loops also have the propertyto stabilize fluctuations of biochemicalparameters29
การแปล กรุณารอสักครู่..
