What is the tyrosine kinase receptor?

The tyrosine kinase receptor represents a membrane-bound receptor, i.e. a receptor anchored in the cell membrane. Structurally, it is a receptor with a transmembrane complex. This means that the receptor passes through the entire cell membrane and also has an extra- and intracellular side.

On the extracellular side, the alpha-subunit, the specific ligand binds to the receptor, while on the intracellular side, the ß-subunit, the catalytic center of the receptor is located. The catalytic center represents the active area of the enzyme where specific reactions take place. As mentioned above, the receptor is structurally composed mostly of two protein subunits (dimer).

In the insulin receptor, for example, the two alpha subunits bind the ligand insulin. After ligand binding, phosphate groups (so-called phosphorylation) are bound to specific tyrosine residues (hydroxy groups). This generates the tyrosine kinase activity of the receptor. In the following, further substrate proteins (e.g. enzymes or cytokines) in the cell interior can be activated or inactivated by means of renewed phosphorylation and thus influence cell proliferation and differentiation.

What is a tyrosine kinase inhibitor?

So-called tyrosine kinase inhibitors (also: tyrosine kinase inhibitors) are relatively new drugs that can be used to treat defective tyrosine kinase activity in a targeted manner. They are classified as chemotherapeutic drugs and have their origin in the late 1990s or early 2000s. They can be classified into different generations and are used in the treatment of malignant diseases.

Functionally, specific processes of dysbalanced tyrosine kinase activities can be inhibited. In principle, four different mechanisms of action are possible. In addition to competing with ATP, binding to the phosphorylating unit of the receptor, on the substrate or allosterically outside the active site is possible.

The effect of tyrosine kinase inhibitors is triggered by binding to the EGF receptor and subsequent inhibition of the enzymatic activity of tyrosine kinases. In the history of medicine, the discovery of the active substance imatinib as a tyrosine kinase inhibitor has achieved an outstanding position. It is used specifically in chronic myeloid leukemia (CML), where it suppresses the tyrosine kinase activity pathologically produced by chromosome fusion (Philadelphia chromosome by fusion of chromosomes 9 and 22). In recent years, several other tyrosine kinase inhibitors have been developed. The currently existing 2nd generation contains about ten tyrosine kinase inhibitors.