Tyrosine kinase

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Tyrosine kinase

A tyrosine kinase is an enzyme

Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
that can transfer a phosphate

Phosphate

A phosphate, an inorganic chemical, is a Salt of phosphoric acid. Inorganic phosphates are mining to obtain phosphorus for use in agriculture and industry....
group from ATP

Adenosine triphosphate

This article is about the chemical used by cells as an energy carrier. For other uses, see ATP .Adenosine-5'-triphosphate is a multifunctional nucleotide, and plays an important role in cell biology as a coenzyme that is the "molecule unit of currency" of intracellular energy transfer....
to a tyrosine

Tyrosine

Tyrosine or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cell to protein biosynthesis proteins. This is a non-essential amino acid and it is found in casein....
residue

Residue (chemistry)

In chemistry, residue refers to the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group....
in a protein

Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
.

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Encyclopedia

A tyrosine kinase is an enzyme

Enzyme

Phosphate

A phosphate, an inorganic chemical, is a Salt of phosphoric acid. Inorganic phosphates are mining to obtain phosphorus for use in agriculture and industry....
group from ATP

Adenosine triphosphate

Tyrosine

Residue (chemistry)

In chemistry, residue refers to the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group....
in a protein

Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
. Tyrosine kinases are a subgroup of the larger class of protein kinase

Protein kinase

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme catalysis, cellular location, or association with other proteins....
s. Phosphorylation

Phosphorylation

Signal transduction

In biology, 'signal transduction' refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemistry chemical reaction inside the cell, which are carried out by enzymes, activated by Second messenger systems, resulting in a signal tran...
for regulation of enzyme activity.

There are over 100 3D structures of tyrosine kinases available at the Protein Data Bank

Protein Data Bank

The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids. . The data, typically obtained by X-ray crystallography or Protein NMR and submitted by biologists and biochemistry from around the world, are released into the public domain, and can be accessed at no charge...
. An example is PDB , the crystal structure of the tyrosine kinase domain of the human insulin receptor

Insulin receptor

In molecular biology, the insulin receptor is a transmembrane receptor receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....
.

Most tyrosine kinases have an associated protein tyrosine phosphatase

Protein tyrosine phosphatase

Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins....
.

They are coupled to nicotinic cholinoceptors.

Groups

The tyrosine kinases are divided into two groups:

those that are cytoplasm
Cytoplasm

The cytoplasm is the part of a Cell that is enclosed within the plasma membrane. In eukaryote cells the cytoplasm contains organelles, such as mitochondrion, that are filled with liquid kept separate from the rest of the cytoplasm by biological membranes....
ic proteins.
the transmembrane
Protein kinase

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme catalysis, cellular location, or association with other proteins....
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

Differentiation

Differentiation can mean the following:* The act of finding the derivative in mathematics* Differentiated instruction in education,* Cellular differentiation in biology...
, metabolism, adhesion, motility, death . 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

Adenosine triphosphate

Substrate (biochemistry)

In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalysis chemical reactions involving the substrate. The substrate binds with the enzyme active site, and an enzyme-substrate complex is formed....
to the active site. This triggers a cascade of events through phosphorylation

Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Protein phosphorylation in particular plays a significant role in a wide range of cellular processes....
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 , 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

Cancer

Cytoplasmic/non-receptor

In humans, there are 32 cytoplasmic protein tyrosine kinases .

The first non-receptor tyrosine kinase identified was the v-src
Src (gene)

Src is a family of proto-oncogene tyrosine kinases originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine....
oncogenic

Oncogene

An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a cancer cell.Many cells normally undergo a programmed form of death ....
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 kinases are particularly important today because of their implications in the treatment of cancer

Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
. A mutation that causes certain tyrosine kinases to be constitutively active has been associated with several cancers. Imatinib

Imatinib

Imatinib is a medication used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate ....
(brand names Gleevec and Glivec) is a drug able to bind the catalytic cleft of these tyrosine kinases, inhibiting its activity.