Biomedical Engineering Reference
In-Depth Information
cancer, and borderline ovarian cancer [14]. The pathway primarily
regulates cell growth and is activated by growth factors released in
the local microenvironment [15]. Proceeding along the transduction
of extra cellular signals into the cell, the major branch point in the
MAPK pathway occurs with RAS, which then activates downstream
pathways, including the BRAF-ERK and phosphtidylinositol-3-
kinase (PI3K)-AKT pathways [16]. Extracellular signals, including
hormones, cytokines and growth factors, interact with receptors
to activate the RAS family, which then acts via adaptor proteins to
recruit RAF proteins to the cell membrane where they are activated
[17].
Figure 17.1
The Raf/MEK/ERK signaling pathway.
The RAF family of serine/threonine kinases has three isoforms,
ARAF, BRAF, and CRAF. While ARAF and CRAF require both activation
by RAS and phosphorylation, BRAF's N-terminus is constitutively
active, needing only RAS and thus fewer steps for activation [18].
Once activated, RAF can then sequentially stimulate MEK1 and MEK2,
which then turn on ERK1 and ERK2. These proceed to activate the
cytoplasm targets or travel to the nucleus to finally phosphorylate
transcription factors [19-21].
Specifically, the structure of MEK 1/2 with their proline-rich
segments in the carboxyl-terminal is thought to play a role in the
