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Tyrosine kinase

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A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein. Tyrosine kinases are a subgroup of the larger class of protein kinases. Phosphorylation of proteins by kinases is an important mechanism in signal transduction for regulation of enzyme activity. The tyrosine kinases are divided into two groups; those that are cytoplasmic proteins and the transmembrane receptor-linked kinases. In humans, there are 32 cytoplasmic protein tyrosine kinases (EC 2.7.10.2) and 58 receptor-linked protein-tyrosine kinases (EC 2.7.10.1). The hormones and growth factors that act on cell surface tyrosine kinase-linked receptors are generally growth-promoting and function to stimulate cell division (e.g., insulin, insulin-like growth factor 1, epidermal growth factor).

General properties

There are over 100 3D structures of tyrosine kinases available at the Protein Data Bank. An example is PDB 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.

Most tyrosine kinases have an associated protein tyrosine phosphatase.

Abl

v-abl Abelson murine leukemia viral oncogene homolog 1
Symbol(s): ABL1 ABL
Locus: 9 q34.1
EC number [1]
EntrezGene 25
OMIM 189980
RefSeq NM_007313
UniProt P00519

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)

v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
Symbol(s): KIT
Locus: 4 q11 -q12
EC number [2]
EntrezGene 3815
OMIM 164920
RefSeq NM_000222
UniProt P10721

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.

Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell.

Sources

See also

ar:تيروزين كيناز de:Tyrosinkinase es:tirosincinasa zh:酪氨酸激酶

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