Tyrosine kinase

Tyrosine kinase

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.

There are over 100 3D structures of tyrosine kinases available at the Protein Data Bank. An example is PDB [http://www.rcsb.org/pdb/cgi/explore.cgi?pid=232131034361062&page=60&pdbId=1IRK 1IRK] , the crystal structure of the tyrosine kinase domain of the human insulin receptor.

Most tyrosine kinases have an associated protein tyrosine phosphatase.

Groups

The tyrosine kinases are divided into two groups:
* those that are cytoplasmic proteins.
* the transmembrane receptor-linked kinases.

Receptor

Approximately 2000 kinases are known and more than 90 Protein Tyrosine Kinases (PTKs) have been found in the human genome. They are divided into two classes, receptor and non-receptor PTKs. At present, 58 receptor tyrosine kinases (RTKs) are known, grouped into 20 subfamilies. They play pivotal roles in diverse cellular activities including growth, differentiation, metabolism, adhesion, motility, death [S B Bhise, Abhijit D. Nalawade and Hitesh Wadhawa, "Role of protein tyrosine kinase inhibitors in cancer therapeutics". Indian Journal of Biochemistry & Biophysics, 2004 Dec; 41: 273-280. ISSN 0301-1208.] .RTKs are composed of an extracellular domain, which is able to bind a specific ligand, a transmembrane domain, and an intracellular catalytic domain, which is able to bind and phosphorylate selected substrates. Binding of a ligand to the extracellular region causes a series of structural rearrangements in the RTK that lead to its enzymatic activation. In particular, movement of some parts of the kinase domain gives free access to adenosine triphosphate (ATP) and the substrate to the active site. This triggers a cascade of events through phosphorylation of intracellular proteins that ultimately transmit ("transduce") the extracellular signal to the nucleus, causing changes in gene expression.Many RTKs are involved in oncogenesis, either by gene mutation, or chromosome translocation [RH Gunby et al. "Oncogenic Fusion Tyrosine Kinases As Molecular Targets for Anti-Cancer Therapy". Anti-Cancer Agents in Medicinal Chemistry, 2007; 7:594-611.] , or simply by over-expression. In every case, the result is a hyper-active kinase, that confers an aberrant, ligand-independent, non-regulated growth stimulus to the cancer cells.

Cytoplasmic/non-receptor

In humans, there are 32 cytoplasmic protein tyrosine kinases (EC number|2.7.10.2).

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".

Clinical significance

Tyrosine kinase is particularly important today because of its implications in the treatment of cancer. A mutation that causes certain tyrosine kinases to be constitutively active has been associated with several cancers. Imatinib (brand names Gleevec and Glivec) is a drug able to bind the catalytic cleft of these tyrosine kinases, inhibiting its activity. [cite book |last= Weinberg|first= Robert A.|origyear= 2007|title= "The Biology Of Cancer"|location= New York|publisher= Garland Science, Taylor & Francis Group, LLC| isbn= 0-8153-4076-1|pages= 757-759]

References


Wikimedia Foundation. 2010.

Игры ⚽ Нужно решить контрольную?

Look at other dictionaries:

  • Tyrosine kinase 2 — Tyrosine kinase 2, also known as TYK2, is a human gene.cite web | title = Entrez Gene: TYK2 tyrosine kinase 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=7297| accessdate = ] Tyk2 was the first member… …   Wikipedia

  • Tyrosine kinase — Récepteur Tyrosine Kinase Pour les articles homonymes, voir RTK. Les Récepteurs à activité Tyrosine Kinase (RTK) font partie de la famille des récepteurs enzymes. Ce sont tous des récepteurs transmembranaires monomérique exception faite pour l… …   Wikipédia en Français

  • tyrosine kinase — Kinases that phosphorylate protein tyrosine residues. These kinases play major roles in mitogenic signalling, and can be divided into two subfamilies: receptor tyrosine kinases, that have an extracellular ligand binding domain, a single… …   Dictionary of molecular biology

  • tyrosine kinase — ty·ro·sine ki·nase (tiґro sēn kiґnās) protein tyrosine kinase …   Medical dictionary

  • tyrosine kinase inhibitor BIBF 1120 — A substance being studied in the treatment of some types of cancer. Tyrosine kinase inhibitor BIBF 1120 blocks enzymes needed for cells to grow, and may prevent the growth of new blood vessels needed for tumors to grow. It is a type of tyrosine… …   English dictionary of cancer terms

  • tyrosine kinase inhibitor — any of a class of antineoplastic agents that inhibit protein tyrosine kinase and interfere with the action of epidermal growth factor in cancer cells …   Medical dictionary

  • tyrosine kinase inhibitor — A drug that interferes with cell communication and growth and may prevent tumor growth. Some tyrosine kinase inhibitors are used to treat cancer …   English dictionary of cancer terms

  • tyrosine kinase phosphorylation site — Substrates of tyrosine protein kinases are generally characterized by a lysine or an arginine seven residues to the N terminal side of the phosphorylated tyrosine, and an acidic residue (Asp or Glu) three or four residues to the N terminal side… …   Dictionary of molecular biology

  • tyrosine kinase inhibitor — any one of a class of drugs that interfere with cell growth in a variety of different ways by inhibiting the action of tyrosine kinases. This family of enzymes, which occur both within cells and as components of cell membrane receptor sites, have …   The new mediacal dictionary

  • Bcr-Abl tyrosine-kinase inhibitor — Bcr Abl tyrosine kinase inhibitors (TKI) are the first line therapy for most patients with chronic myelogenous leukemia (CML). In more than 90% cases CML is caused by chromosomal abnormality resulting in the formation of a so called Philadelphia… …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”