Tyrosine kinase

Tyrosine kinases are a group of enzymes from the family of protein kinases whose task the reversible transfer of a phosphate group (phosphorylation ) is due to the hydroxyl group of the amino acid tyrosine of another protein. Thus, the activity of the target protein is significantly affected, which is why tyrosine kinases play an important role for signal transmission and as part of receptor systems.

Breakdown of tyrosine kinases

Operation of a tyrosine kinase receptor with intrinsic activity

Binds an appropriate ligand to the receptor then its spatial conformation changes (protein structure). The formation of homodimers ( two equal annealed receptors) or heterodimers ( two different protein subunits self-assemble ) is induced. This causes the tyrosine kinases, sitting at the cytosolic part of the receptor is activated and are specific for phosphate groups to specific tyrosine residues of the receptor. This means that in these phosphorylated residues can bind to proteins with SH2 domains, which leads to the recruitment of intracellular activation pathways. The so- recruited proteins have either themselves enzymatic activity ( phospholipase C- γ, PI3- kinase ) and so can phosphorylate other proteins, for example, or represent intermediaries whose structural change is recognized by other molecules ( Ras ). This leads to a cascade of transmission and amplification of the signal, as an activated protein, in turn, activates a plurality of the proteins of the next stage of the signal path, etc.

Short form:

Functioning of a receptor tyrosine kinase associated with

Binds an appropriate ligand to the receptor then its spatial conformation changes (protein structure). The formation of homodimers ( two equal annealed receptors) or heterodimers ( two different protein subunits self-assemble ) is induced. Thereby, the Janus kinases are closer to each other and then phosphorylate each other ( autophosphorylation ). Now present in the activated state, these proteins phosphorylate tyrosyl residues of the receptor to the specific transcription factors can now be deposited (e.g., STAT) with SH2 domains. These factors are phosphorylated by Janus kinases and dimerize and thereby show a higher DNA affinity.

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Medical Outlook

The addition of a phosphate residue can activate or inactivate a protein. Tyrosine kinases also form the intracellular portion of the Tyrosinkinaserezeptorsystems (insulin receptor, EGF receptor, NGF receptor, PDGF receptor ), preferably shrink signals of growth factors on the. This makes them a sought-after goal of the research for new cancer drugs. Cell- receptor -linked tyrosine kinases are important in embryonic development and the regeneration and maintenance of tissues. Disturbances of its function are mitverursachend for diseases of the retina in diabetes mellitus, atherosclerosis, and especially they play in the development of cancer a role ( ie, on the induction of a malignant, no longer completely controllable in their growth, cell change ). Tyrosine kinases are activated by the presence of various growth factors. A mutant cell- bound receptor tyrosine kinase is able to simulate the presence of growth factors and as a cofactor to cell proliferation, and finally work towards a malignant cell transformation. Tyrosine kinase inhibitors are a class of novel drugs. For example, the step of extra according to the inhibition of tyrosine kinase in signal transduction can be inhibited intracellular and widen existing treatment options for individual cancers sense. This is especially true for patients with chronic myeloid leukemia ( CML), advanced non- small cell lung cancer ( NSCLC) or gastrointestinal stromal tumors ( GIST).