Receptor tyrosine kinases are membrane spanning receptors.
Phosphorylation of a substrate by tyrosine kinase acts a switch to
trigger downstream cellular responses such as cell cycle progression.
When a growth factor binds to a receptor tyrosine kinase, it
forms a complex with another receptor tyrosine kinase. This
dimerization leads to phosphorylation of the activated receptor.
Specific proteins that bind tyrosine residues within the activated
receptor include Src and phospholipase Cγ.
Unlike Receptor Tyrosine Kinases, some receptors have no catalytic activity and rely on other tyrosine kinases, such as JAK.
Families
Epidermal growth factor receptor family
The ErbB protein family or epidermal growth factor
receptor (EGFR) family is a family of transmembrane proteins that
are structurally related receptor tyrosine kinsases. Binding of
EGFR to its ligands leads to autophosphorylation of receptor
tyrosine kinase and subsequent activation of signal transduction
pathways that are involved in regulating cellular proliferation,
differentiation, and survival.
Insufficient EGF signaling in humans is associated with the
development of neurodegenerative diseases, such as multiple
sclerosis and Alzheimer's Disease. In mice, loss of signaling by
any member of the EGF family results in the death of the embryo.
Excessive EGF signaling is associated with the development of a
wide variety of types of solid tumor. Although present in normal
cells, EGFR is overexpressed in a variety of tumor cell lines and
has been associated with poor prognosis and decreased survival.
EGFR activation also plays a role in resistance to chemotherapy
and radiation treatment in tumor cells.
Fibroblast growth factor receptor (FGFR) family
The family of fibroblast growth factors (FGFs) regulates many
developmental processes, including brain patterning and limb
development.
FGF receptor kinase inhibitors are being studied in the
treatment of cancer and cardiovascular disease and have shown
potential in the treatment of metabolic syndrome and
hypophosphataemic diseases.
Each receptor can be activated by several FGFs.
Vascular endothelial growth factor receptor (VEGFR)
family
Vascular endothelial growth factor (VEGF)
is a protein that triggers cell division (mitosis) for cells that
line the circulatory system and also induces the flow of water,
nutrients, etc. in and out of the blood vessel.
Tumors induce blood vessel growth by secreting various growth
factors such as VEGF. Some researchers believe these blood vessels
supply required nutrient growth. Inhibition of VEGF signaling
stops development of a wide variety of tumors.
Two receptor tyrosine kinases bind to VEGF at the cell surface.
RET Receptor family
The RET
receptor is a tyrosine kinase that binds members of the glial cell
line-derived neurotrophic factor (GDNF) which promotes survival of
a variety of neurons and activates a signaling network crucial
for neural and kidney development.
Eph Receptor Family
Eph receptor
(erythropoietin-producing human hepatocellular carcinoma) tyrosine
kinases affect many biological processes by binding ephrins. Eph
signals affect cells that are in contact with one another and may
account for the various effects on axon guidance, cell adhesion
and cell migration. The Eph receptor/ephrin system has been
implicated in immune regulation as well as in central nervous
system injury and disease. A role for the Eph receptor/ephrin
system has also emerged in cancer.
