INVESTIGADORES
VENTURA Alejandra Cristina
congresos y reuniones científicas
Título:
The role of scaffold proteins in information transfer in cellular signaling
Autor/es:
VERONICA PARASCO; JACQUES-A. SEPULCHRE; ALEJANDRO COLMAN-LERNER; ALEJANDRA C VENTURA
Lugar:
Buenos Aires
Reunión:
Otro; V Escuela de invierno Luis A Santalo; 2012
Institución organizadora:
Departamento de Matemática de la Facultad de Ciencias Exactas y Naturales de la Universidad de Buenos
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.
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.