EPIDERMAL GROWTH FACTOR (EGF) RECEPTOR SIGNALING AND CANCER Introduction

EPIDERMAL GROWTH FACTOR (EGF) RECEPTOR SIGNALING AND CANCER

Table of ContentsIntroduction.................................................................................................................................................2
ErbB receptor family and ligands................................................................................................................2
General ErbB receptor signal transduction pathway....................................................................................2
RAS/ERK pathway......................................................................................................................................3
Negative regulation of RAS/ERK pathway.................................................................................................4
PI3/AKT pathway........................................................................................................................................4
Activation of PI3K:.................................................................................................................................4
Formation of PIP3 and activation of AKT:..............................................................................................4
Downstream signaling:............................................................................................................................4
Negative regulation PI3/AKT pathway.......................................................................................................5
JAK/STAT pathway....................................................................................................................................5
Negative regulation of JAK/STAT pathway................................................................................................5
ErbB receptors and cancer...........................................................................................................................5
Cancers due to ErbB receptor mutation.......................................................................................................5
Therapies and treatment...............................................................................................................................6
Monoclonal antibodies:...........................................................................................................................6
Tyrosine kinase inhibitors:......................................................................................................................6
Combination of therapies:........................................................................................................................6
Conclusion...................................................................................................................................................6
References...................................................................................................................................................7
Table of figures:
Figure 1: General signal transduction pathway...........................................................................................3
Figure 2: RAS/ERK pathway.........................................................................................................................3
Figure 3: Activation of PI3K..........................................................................................................................4
Figure 4: Formation of PIP3K and activation of AKT....................................................................................4
Figure 5: Downstream signaling..................................................................................................................4
Figure 6: JAK/STAT pathway........................................................................................................................5
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Introduction
Epidermal growth factor receptor is the best understood of tyrosine kinase receptor family, which
is also known as ErbB receptor family. Activation of domain occurs when growth factor binds to
receptor and as a result autophosphorylation after which intracellular signaling occurs. Many
growth factors including EGF bind to these receptors. MAPK pathway, JAK/STAT pathway and
PI3/AKT pathway; these all are activated by this receptor family. In cancer, deregulation of
receptors occurs due to overexpression or mutation. Due to which signaling increases and as a
result more proliferation occur.
ErbB receptor family and ligands
This receptor family is made of four receptors and specific ligands family binds to them which
are following:
ErbB1:
This receptor binds with TGF-α, epigen, EGF etc.
ErbB2:
This receptor binds with no ligand. Because ErbB2 receptor doesn’t have any domain and this
receptor works by interacting with other receptors.
ErbB3:
This receptor binds with neuregulin 1,2.
ErbB4:
This receptor binds with epigen, tomoregulin and betacellulin.
General ErbB receptor signal transduction pathway
In signal transduction pathway, first of all ligand binds with the receptor, which leads to the
autophosphorylation of receptor. After that adaptor proteins bind to the receptor and form a
signal transduction complex. These adaptor proteins activate a kinase and then that kinase
phosphorylates and activates another kinase. As a result, process such as cell survival,
differentiation and proliferation occur.
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