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Receptor Tyrosine Kinases

Examples of receptor tyrosine kinases are the insulin receptor, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and Eph. A kinase is an enzyme that transfers phosphate groups to specific molecules. Kinases that transfer phosphate groups from the amino acid tyrosine are called tyrosine kinases.

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.

Receptor tyrosine kinases are cell surface receptors. Other receptors in this category are ligand gated ion channels, toll like receptors, integrins and G protein coupled receptors.

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Introduction to Receptors

Receptors:

G Protein Coupled Receptors
Receptor Tyrosine Kinase
Toll-like Receptors
Ligand-Gated Ion Channels
Integrins

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The Basics of Cell Surface Receptors
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Episode 5 - Let's Be Aware