Tyrosine kinases

Transfer phosphate from adenosine triphosphate to tyrosine residues in specific substrate proteins.

They are enzymes which is capable of adding a phosphate group to certain tyrosines on target proteins, or substrates.


Tyrosine kinase is an enzyme which is capable of adding a phosphate group to certain tyrosines on target proteins, or “substrates”. 


A receptor tyrosine kinase is a “tyrosine kinase” which is located at the cellular membrane, and is activated by binding of a ligand to the receptor’s extracellular domain.


Family of proteins that regulate cell to cell signals.

Provide docking sites for adapter proteins and signaling enzymes which activate many downstream signaling pathways.

A family of proteins that facilitates the coordination of cell growth.

Regulators of intracellular signal transduction pathways mediating cellular development and multicellular communications.

Examples of tyrosine kinase receptors include the insulin receptor, the IGF1 receptor, the MuSK protein receptor, the Vascular Endothelial Growth Factor (or VEGF) receptor, and TrkB receptor.

The process of tumorigenesis frequently involves protein kinase activation events, which can result from either mutations, or chromosomal rearrangements.

Gene rearrangements, leading to the expression of constitutively activated fusion tyrosine kinase receptors, have been increasingly identified as a common feature of malignancies over the last three decades, and success has been demonstrated using these rearrangements as targets for drug development.

By attaching phosphate groups to the amino acid in tyrosine in proteins they help control key cellular processes such as the cell cycle, metabolism, and apoptosis.

The subset of tyrosine kinases with extracellular domains that bind growth factors, which trigger cytosolic tyrosine kinase activity, are referred to as receptor tyrosine kinases (RTKs).

Examples of RTKs include the epidermal growth factor receptor, platelet derived growth factor receptor, and insulin receptor,


Activation of intracellular tyrosine kinase by these growth factors initiate events that induce nutrient uptake, macromolecules synthesis, and proliferation.

When activated lead to increased tumor cell proliferation, tumor growth, induces anti-apoptotic effects, promotes angiogenesis and metastases.

When activated by somatic medications may have a role initiating the genesis of tumors.

Approximately 90 tyrosine kinases and 43-tyrosine kinase like genes in the human genome and they are divided into receptor and nonreceptor types.

Abnormal activation or signaling of tyrosine kinase pathways play a role in many malignancies.

Normally ligand binding tightly regulates kinase activity, but mutations and aberrant expressions may set off intracellular cascade of signaling events that may promote unregulated cell growth.

Consist of an extracellular ligand binding domain, a transmembrane domain in the lipid bilayer and an intracellular cytoplasmic domain.

These enzymes catalyze the gamma phosphate group from adenosine triphosphate to target proteins and are involved in many normal cellular regulatory processes.

There are 2 subgroups: Receptor tyrosine kinases and non-receptor tyrosine kinases.

Receptors are not fixed in one place on the cell membrane and with ligand binding to the extracellular domain dimerization results.

The receptor tyrosine kinases on membrane spanning cell surface proteins comprising an extracellular N-terminal that binds to a ligand, and a C-terminal region that autophosphorylates creating binding sites.

Binding of the ligand to the extracellular receptor activates tyrosine kinase activity.

Non-receptor tyrosine kinases relay intracellular signals that result in DNA synthesis, cell division, cell growth, cell migration, differentiation and death.

Dimerization that results from ligand binding can be homodimers or heterodimers, and the type of dimerization can effect downstream functions.

Following ligand binding and dimerization intracellular cytoplasmic tyrosine kinase domain is activated and phosphorylation occurs.

In malignant cells, the C-terminal domain may be mutated, so that kinases continue to be activated.

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