An overwhelming body of data unquestionably links the Ras-ERK
pathway to the upbringing and progression of human malignancies.
About 40% of human cancers harbor activating mutations in proteins
involved in this signaling cascade, in particular Ras and Braf. In addition
to the main proteins of this signaling pathway, there are several
regulatory proteins known as scaffold proteins, that modulate the
intensity, amplitude and duration of ERK signals. Interestingly, it can
propose the scaffold proteins as antitumoral targets. Considering the
hypothesis that scaffold proteins interact and regulate the signal
transduction through the Ras-ERK pathway in a coordinated manner
we try to find out how these interactions are regulated. Ras proteins
are distributed in different types of plasma membrane: microdomains
and endomembranes. We have previously demonstrated that
compartmentalization dictates Ras utilization of effectors, the intensity
of its signals and the biological response of the cells. Cell migration is
critical for many physiological processes and is often misregulated in
developmental disorders and pathological conditions including cancer.
MAPK signaling are known regulators of cytoskeletal dynamics during
cellular processes such as cell adhesion and migration. Our hypothesis
is that localized ERK signaling mediated through recently identified
scaffold proteins and its interactions with the cytoskeleton may
regulate specific cellular responses. Here we propose that associations
among different scaffold proteins and cytoskeleton will add one further
degree of regulation for an already tightly regulated cascade and could
provide a novel means for manipulating ERK signals, even with
therapeutic purposes.
