Tyrosine kinase
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- Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation
A tyrosine kinase (EC 2.7.1.112) is an enzyme that can transfer a phosphate group to a tyrosine residue in a protein; these enzymes are a subgroup of the larger class of protein kinases. Phosphorylation is an important function in signal transduction to regulate enzyme activity. The hormones that act on tyrosine kinase receptors are generally growth hormones and factors that promote cell division (e.g., insulin, insulin-like growth factor 1, epidermal-derived growth factor).
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General properties
There are over 100 3D structures of tyrosine kinases available at the Protein Data Bank. An example is PDB 1IRK (http://www.rcsb.org/pdb/cgi/explore.cgi?pid=232131034361062&page=60&pdbId=1IRK), the crystal structure of the tyrosine kinase domain of the human insulin receptor.
The first non-receptor tyrosine kinase identified was the v-Src oncogenic protein. Most animal cells contain one or more members of the Src family of tyrosine kinases. A chicken sarcoma virus was found to carry mutated version of the normal cellular Src gene. The mutated v-src gene has lost the normal built-in inhibition of enzyme activity that is characteristic of cellular SRC (c-src) genes. SRC family members have been found to regulate many cellular processes. For example, the T-cell antigen receptor leads to intracellular signalling by activation of Lck and Fyn, two proteins that are structurally similar to Src.
Abl
Abl (Abelson leukemia virus protein, chromosome 9q34) is an important tyrosine kinase. This gene is fused with the bcr gene in a Philadelphia chromosome, the characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. The bcr-abl transcript is also a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. The bcr-abl protein can be inhibited with the agent imatinib mesylate, which occupies the TK domain and inhibits bcr-abls influence on the cell cycle.
c-kit (CD117)
This CD molecule is the membrane receptor for stem cell factor (SCF), also known as "steel factor" or "c-kit ligand". Steel factor is a polypeptide that activates bone marrow precursors of a number of blood cells, but its receptor is also present on other cells. C-kit mutations in the interstitial cells of Cajal in the digestive tract are probably the key to gastrointestinal stromal tumors (GISTs), and explain the efficacy of imatinib in the management of these rare malignancies.
Sources
- Template:OMIM (ABL)
- Template:OMIM (BCR)