Biomedical Engineering Reference
In-Depth Information
Figure 6.1
The EGFR Pathway. EGFR signaling commences with the binding
of ligand (e.g. EGF, TGF-α) to the EGFR receptor. This leads to
dimerization, with one part being EGFR and the other part
being one of EGFR, HER2, ErbB3 or ErbB4. Dimerization leads
to the activation of the intracellular tyrosine kinase domains
through autophosphorylation. Through docking proteins,
both the RAS/RAF/MAPK pathways and PI3K/Akt pathways
are activated. Activation of these pathways leads to cell cycle
progression, increased cell division, increased cell survival and
increased probability of metastasis. EGFR also activates the
STAT protein family in the cytosol. This leads to translocation
into the nucleus and further transcription regulation.
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6.3
Signal Transduction Pathways Controlled by
the Activation of EGFR
A schematic of the signal transduction pathways under the control of
EGFR is shown in (Fig. 6.1). Overall, two major pathways are involved:
the RAS-RAF-MAPK (Ras) pathway and the phosphoinositol-3-
phosphate-Akt (PI3K) pathway. For the Ras pathway, activated EGFR
recruits Ras and initiates activation through the exchange of guanine
diphosphate (GDP) to guanine triphosphate (GTP).
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This leads to
signal transduction and transcription of genes controlling cycle-cycle
