Tyrosine kinases

Group of enzymes from the protein kinase family (transferases) whose task is the reversible transfer of a phosphate group (phosphorylation) to the hydroxyl group of the amino acid tyrosine of another protein. This influences the activity of the target protein.

The group of tyrosine kinases makes an important contribution to signal transduction. It includes about 100 different enzymes.

Tyrosine kinases can be classified as follows:

• Receptor tyrosine kinases(EC class 2.7.10.1)
  • tyrosine kinases which are part of a transmembrane receptor (receptors with intrinsic tyrosine kinase activity)
  • Tyrosine kinases that bind to a transmembrane receptor (receptors with associated tyrosine kinase activity)
• Cytoplasmic (cytosolic) tyrosine kinases (non-receptor tyrosine kinases, EC class 2.7.10.2)

Cell receptor bound tyrosine kinases are important for embryonic development and the regeneration and maintenance of tissues. Disturbances of their function are partly responsible for diseases of the retina in diabetes mellitus, arteriosclerosis and above all they play an important role in the malignant transformation of cells.

Tyrosine kinases are activated by various growth factors, e.g. EGF (epidermal growth factor). A mutated tyrosine kinase can simulate the presence of growth factors and thus act as a cofactor for cell proliferation and eventually malignant cell transformation.

Mutations of the tyrosinase genes can lead to constitutive activation of the incorrectly coded enzyme "tyrosine kinase". The consequence is, i.e. that the downstream signalling pathway is constantly "activated". This constant activation of the signaling pathway can lead to uncontrolled (tumorous) cell growth. Tyrosine kinases that are activated in such a faulty and uncontrolled manner play a decisive role in the survival of tumor cells. In this respect, tyrosine kinases are important "targets" for specific biological oncological drugs (tyrosine kinase inhibitors as "targeted therapy" - Peters G 2019).

Inhibitors of tyrosine kinase(tyrosine kinase inhibitors e.g. imatinib) are highly interesting drugs whose therapeutic possibilities have been evaluated in various studies. In signal transduction, tyrosine kinase inhibitors inhibit the step from extra- to intracellular and thus open up therapeutic options for various tumor diseases.

Tyrosine kinase inhibitors could also play a role in the treatment of chronic graft-versus-host disease and systemic scleroderma.

1. Gabrielli A et al (2007) Stimulatory autoantibodies to the PDGF receptor: a link to fibrosis in scleroderma and a pathway for novel therapeutic targets. Autoimmune Rev 7: 121-126
2. Gabrielli A et al (2007) Pathogenic autoantibodies in systemic sclerosis. Curr Opin Immunol 19: 640-645
3. Peter's GJ (2019) From 'Targeted Therapy' to Targeted Therapy. Anticancer Res 39:3341-3345.
4. Svegliati S et al (2007) Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood 110: 237-241