IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
Long signaling cascades tend to attenuate retroactivity
Autor/es:
HR OSSAREH; ALEJANDRA C VENTURA; SD MERAJVER; DOMITILLA DEL VECCHIO
Revista:
BIOPHYSICAL JOURNAL
Editorial:
CELL PRESS
Referencias:
Año: 2011 vol. 100 p. 1617 - 1626
ISSN:
0006-3495
Resumen:
Signaling pathways consisting of phosphorylation/dephosphorylation
cycles with no explicit feedback allow signals to propagate not only
from upstream to downstream but also from downstream to upstream due to
retroactivity at the interconnection between
phosphorylation/dephosphorylation cycles. However, the extent to which a
downstream perturbation can propagate upstream in a signaling cascade
and the parameters that affect this propagation are presently unknown.
Here, we determine the downstream-to-upstream steady-state gain at each
stage of the signaling cascade as a function of the cascade parameters.
This gain can be made smaller than 1 (attenuation) by sufficiently fast
kinase rates compared to the phosphatase rates and/or by sufficiently
large Michaelis-Menten constants and sufficiently low amounts of total
stage protein. Numerical studies performed on sets of biologically
relevant parameters indicated that ∼50% of these parameters could give
rise to amplification of the downstream perturbation at some stage in a
three-stage cascade. In an n-stage cascade, the percentage of parameters
that lead to an overall attenuation from the last stage to the first
stage monotonically increases with the cascade length n and reaches 100%
for cascades of length at least 6.