IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The role of scaffold proteins in information transfer in cellular signaling
Autor/es:
VERONICA PARASCO; ALEJANDRO COLMAN-LERNER; ALEJANDRA C VENTURA
Lugar:
Buenos Aires
Reunión:
Simposio; Frontiers in BioScience; 2012
Institución organizadora:
Max Planck Society and the Ministry of Science, Technology and Innovation
Resumen:
Cell
signaling is carried out by a complex network of interactions between
metabolites, proteins and nucleic acids. Different isolated components from the
signaling network have been extensively studied and characterized in order to
then predict the behavior of the integrated system from the behavior of its
parts. This notion is based on the hypothesis that the properties of the
individual components are not altered as these are interconnected, which is
known as "modular organization". However, our work and that of others1,
2,3,4 has shown theoretically and experimentally (both in vitro and in vivo) that bio-molecular systems cannot always be connected
modularly: the dynamics of the interconnection, which is inherent to the
physics of the system, can dramatically change the behavior of connected
modules, an effect that has been called retroactivity.
Mammalian
cells contains an estimated 1 trillion of protein molecules with approximately
10% of which are involved in signal transduction. Given the enormous number of
molecules, it is surprising that cells can accurately process the large amount
of information they receive constantly. How do signaling proteins find each
other among so many proteins? In the recent decades the notion that cells
organize subgroups of proteins in space and time has appeared. In this
direction and about 15 years ago, the first scaffold proteins were discovered.
Bringing
together the two concepts previously outlined, modular organization and
retroactivity on one side and scaffold proteins on the other, the following
questions arise: does the behavior of a signaling module change if it is integrated
into a scaffold protein?, what is the relationship between scaffold proteins
and retroactivity? In this project, we characterize the interaction between
scaffold proteins and retroactivity through a combination of analytical and
computational tools.
References:
1. Ventura AC, Sepulchre J,
and Merajver SD. A hidden feedback in signaling cascades is revealed. PLoS
Comput Biol, 4(3), 2008.
2.
Del Vecchio D, Ninfa AJ, and Sontag ED. Modular cell biology:
Retroactivity and insulation. Nature/EMBO Molecular Systems Biology, 4:161,
2008.
3. Ventura AC, Jiang
P, Van Wassenhove L, Del Vecchio D, Merjaver SD, and Ninfa AJ. Signaling
properties of a covalent modification cycle are altered by a downstream target,
Proc Natl Acad Sci USA.107(22):10032-7,
2010.
4. Kim Y,
Paroush Z, Nairz K, Hafen E, Jiménez G, Shvartsman SY. Substrate-dependent
control of MAPK phosphorylation in vivo.
Mol Syst Biol. 7:467, 2011.