Tyrosine kinase
Encyclopedia
A tyrosine kinase is an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that can transfer a phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

 group from ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 to a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 in a cell. It functions as an "on" or "off" switch in many cellular functions.

The phosphate group is attached to the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

 on the protein. 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 activity, cellular location, or association with other proteins...

s which attach phosphate groups to other amino acids (serine and threonine
Serine/threonine-specific protein kinase
Serine/threonine protein kinases phosphorylate the OH group of serine or threonine .At least 125 of the 500+ human protein kinases are serine/threonine kinases .-Regulation:...

). Phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 of proteins by kinases is an important mechanism in communicating signals within a cell (signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

) and regulating cellular activity, such as cell division.

Protein kinases can become mutated, stuck in the "on" position , and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Therefore, kinase inhibitors, such as imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...

, are often effective cancer treatments.

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. Protein tyrosine phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular...

, which removes the phosphate group.

Reaction

Protein kinases are a group of enzymes that possess a catalytic subunit that transfers the gamma (terminal) phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. The enzymes fall into two broad classes, characterised with respect to substrate specificity: serine/threonine specific
Serine/threonine-specific protein kinase
Serine/threonine protein kinases phosphorylate the OH group of serine or threonine .At least 125 of the 500+ human protein kinases are serine/threonine kinases .-Regulation:...

 and tyrosine specific (this domain).

Function

The term kinase describes a large family of enzymes that are responsible for catalyzing the transfer of a phosphoryl group from a nucleoside triphosphate donor, such as ATP, to an acceptor molecule. Tyrosine kinases catalyze the phosphorylation of tyrosine residues in proteins. The phosphorylation of tyrosine residues in turn cause a change in the function of the protein that they are contained in.

Phosphorylation at tyrosine residues controls a wide range of properties in proteins such as enzyme activity, subcellular localization, and interaction between molecules. Furthermore tyrosine kinases function in many signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 cascades wherein extracellular signals are transmitted through the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 to the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

 and often to the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 where gene expression may be modified. Finally mutations can cause some tyrosine kinases to become constitutively active, a nonstop functional state that may contribute to initiation or progression of cancer.

Tyrosine kinases function in a variety of processes, pathways, and actions, and is responsible for key events in the body. The receptor tyrosine kinases function in transmembrane signaling, whereas tyrosine kinases within the cell function in signal transduction to the nucleus. Tyrosine kinase activity in the nucleus involves cell-cycle control and properties of transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

s. In this way, in fact, tyrosine kinase activity is involved in mitogenesis, or the induction of mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 in a cell; proteins in the cytosol and proteins in the nucleus are phosphorylated at tyrosine residues during this process. Cellular growth and reproduction may rely in some part on tyrosine kinase. Tyrosine kinase function has been observed in the nuclear matrix
Nuclear matrix
In biology, the nuclear matrix is the network of fibres found throughout the inside of a cell nucleus and is somewhat analogous to the cell cytoskeleton...

, which is comprised not of chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

, but of the nuclear envelope
Nuclear envelope
A nuclear envelope is a double lipid bilayer that encloses the genetic material in eukaryotic cells. The nuclear envelope also serves as the physical barrier, separating the contents of the nucleus from the cytosol...

 and a “fibrous web” that serves to physically stabilize DNA. More specifically, Lyn
LYN
Tyrosine-protein kinase Lyn is a protein that in humans is encoded in humans by the LYN gene.Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells, in neural tissues liver, and adipose tissue. In various hematopoietic cells, Lyn has emerged...

, a type of kinase in the Src
Src (gene)
Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...

 family that was identified in the nuclear matrix, appears to control the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

. Src family tyrosine kinases are closely related, but demonstrate a wide variety of functionality. Roles or expressions of Src family tyrosine kinases vary significantly according to cell type, as well as during cell growth and differentiation. Lyn and Src family tyrosine kinases in general have been known to function in signal transduction pathways. There is evidence that Lyn is localized at the cell membrane; Lyn is associated both physically and functionally with a variety of receptor molecules.

Fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

s – a type of cell that synthesizes the extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...

 and collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...

 and is involved in wound healing – that have been transformed by the polyomavirus
Polyomavirus
Polyomavirus is the sole genus of viruses within the family Polyomaviridæ. Murine polyomavirus was the first polyomavirus discovered by Ludwik Gross in 1953. Subsequently, many polyomaviruses have been found to infect birds and mammals...

 possess higher tyrosine activity in the cellular matrix. Furthermore, tyrosine kinase activity has been determined to be correlated to cellular transformation. It has been also been demonstrated that phosphorylation of a middle-T antigen on tyrosine is also associated with cell transformation, a change that is similar to cellular growth or reproduction.

The transmission of mechanical force and regulatory signals are quite fundamental in the normal survival of a living organism. Protein tyrosine kinase plays a role in this task, too. A protein tyrosine kinase called pp125
PTK2
PTK2 protein tyrosine kinase 2 , also known as Focal Adhesion Kinase , is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes...

 is likely at hand in the influence of cellular focal adhesions, as indicated by an immunofluorescent localization of the said kinase. Focal adhesions are macromolecular structures that function in the transmission of mechanical force and regulatory signals. Among the scientific community, pp125 is also referred to as FAK (focal adhesion kinase), due to its aforementioned presence in cellular focal adhesions. The protein tyrosine kinase pp125 is one of the major phosphotyrosine–containing proteins in unaffected (untransformed) avian and rodent fibroblast cells (fibroblast cells are explained above in some detail). Fibroblasts are a cell type responsible for wound healing and cell structure in animals, among a number of other relatively minor but important jobs that take place often or occasionally. The sequence and structure of pp125, when compared to National Biomedical Research Foundation and GenBank data bases, may be quite unique, meaning it could be a new member of the protein tyrosine kinase family. This protein tyrosine kinase is up to about 70% unique compared to some other protein tyrosine kinases, a figure that is unlike those between actual members of an established protein tyrosine kinase family. Also, the amino acid sequence that was observed indirectly signifies that it is associated with the cytoplasm, dubbing it one in a large group of cytoplasmic protein tyrosine kinases. It was discovered when monoclonal antibodies were observed to recognize it. Monoclonal antibodies, from chicken embryo cells transformed by pp60v-src, recognize seven different phosphotyrosine-containing proteins. One of these monoclonal antibodies, named 2A7, recognizes pp125, support for the idea that pp125 is, in fact, a protein tyrosine kinase.

Cellular proliferation, as explained in some detail above, may rely in some part on tyrosine kinase. Tyrosine kinase function has been observed in the nuclear matrix. Lyn, the type of kinase that was the first to be discovered in the nuclear matrix, is part of Src family of tyrosine kinases, which can be contained in the nucleus of differentiating, calcium-provoked kertinocytes. Lyn, in the nuclear matrix, among the nuclear envelope and the “fibrous web” that physically stabilizes DNA, was found functioning in association with the matrix. Also, it appeared to be conditional to cell cycle. The contribution of the Lyn protein to the total tyrosine kinase activity within the nuclear matrix is unknown, however; because the Lyn was extracted only partially, an accurate measurement of its activity could not be managed. Indications, as such, are that, according to Vegesna et al. (1996), Lyn polypeptides are associated with tyrosine kinase activity in the nuclear matrix. The extracted Lyn was enzymatically active, offering support for this notion.

Yet another possible and probable role of protein tyrosine kinase is that in the event of circulatory failure and organ dysfunction caused by endotoxin in rats, where the effects of inhibitors tyrphostin and genistein
Genistein
Genistein is one of several known isoflavones. Isoflavones, such as genistein and daidzein, are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, also in the medicinal plant, Flemingia vestita and coffee Besides functioning as...

 are involved with protein tyrosine kinase. As has become clear among many people, tyrosine kinase can be involved in some unfortunate things.

Tyrosine kinase is also involved in signaling. Signals in the surroundings received by receptors in the membranes of cells are transmitted into the cell cytoplasm. Transmembrane signaling due to receptor tyrosine kinases, according to Bae et al. (2009), relies heavily on interactions, for example, mediated by the SH2 protein domain; it has been determined via experimentation that the SH2 protein domain selectivity is functional in mediating cellular processes involving tyrosine kinase. Receptor tyrosine kinases may, by this method, influence growth factor receptor signaling. This is one of the more fundamental cellular communication functions metazoans.

Inhibitors

To reduce enzyme activity, inhibitor molecules bind to enzymes. Reducing enzyme activity can disable a pathogen or correct an incorrectly function system; as such, many enzyme inhibitors are developed to be used as drugs for the general public.

GIST and Imatinib

Gastrointestinal stromal tumor
Gastrointestinal stromal tumor
A gastrointestinal stromal tumor is one of the most common mesenchymal tumors of the gastrointestinal tract...

s (GIST) are mesenchymal tumors that affect the gastrointestinal tract.. Treatment option have been limited. However Imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...

, as an inhibitor to the malfunctioning enzyme, can be effective.

Chronic myelogenous leukemia and nilotinib

If Imatinib doesn’t work, patients with advanced chronic myelogenous leukemia
Chronic myelogenous leukemia
Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood...

 can use nilotinib
Nilotinib
Nilotinib , in the form of the hydrochloride monohydrate salt, is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia.-Uses:...

, another inhibitor to the malfunction enzyme that causes the leukemia. This inhibitor is a highly selective Bcr-Abl tyrosine kinase inhibitor.

Others

Sunitinib
Sunitinib
Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that was approved by the FDA for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor on January 26, 2006...

 is an oral tyrosine kinase inhibitor that acts upon vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor
Platelet-derived growth factor receptor
Platelet-derived growth factor receptors are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including...

 (PDGFR), stem cell factor receptor, and colony-stimulating factor-1 receptor (Burstein et al. 2008)

Gefitinib
Gefitinib
Gefitinib INN , trade name Iressa, is a drug used in the treatment of certain types of cancer, particularly those with mutated and overactive EGFR. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor in target cells...

 and Erlotinib
Erlotinib
Erlotinib hydrochloride is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor . It is marketed in the United States by Genentech and OSI...

 inhibit the tyrosine kinase domain of epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

 (EGRF), and can be used to treat lung and pancreatic cancer where there is often over-expression of this cell-surface receptor tyrosine kinase.

Kinase inhibitors can also be mediated. Paracrine signalling
Paracrine signalling
Paracrine signalling is a form of cell signalling in which the target cell is near the signal-releasing cell.-Local action:Some signalling molecules degrade very quickly, limiting the scope of their effectiveness to the immediate surroundings...

 mediates the response to epidermal growth factor receptor kinase inhibitors. Paracrine activates epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

 in endothelial cells of the tumor to do this.

Regulation

Major changes are sometimes induced when the tyrosine kinase enzyme is affected by other factors. One of the factors is a molecule that is bound reversibly by a protein, called a ligand. A number of receptor tyrosine kinases, though certainly not all, do not perform protein-kinase activity until they are occupied, or activated, by one of these ligands. It is interesting to note that, although many more recent cases of research indicate that receptors remain active within endosomes, it was once thought that endocytosis caused by ligands was the event responsible for the process in which receptors are inactivated. Activated receptor tyrosine kinase receptors are internalized (recycled back into the system) in short time and are ultimately delivered to lysosomes, where they become work adjacent to the catabolic acid hydrolases that partake in digestion. Internalized signaling complexes are involved in different roles in different receptor tyrosine kinase systems, the specifics of which was researched. Additionally, ligands participate in reversible binding, a term that describes those inhibitors that bind non-covalently (inhibition of different types are effected depending on whether these inhibitors bind the enzyme, the enzyme-substrate complex, or both). Multivalency, which is an attribute that bears particular interest to some people involved in related scientific research, is a phenomenon characterized by the concurrent binding of several ligands positioned on one unit to several coinciding receptors on another. In any case, the binding of the ligand to its partner is apparent owing to the effects that it can have on the functionality of many proteins. Ligand-activated receptor tyrosine kinases, as they are sometimes referred to, demonstrate a unique attribute. Once a tyrosine receptor kinase is bonded to its ligand, it is able to bind to tyrosine kinase residing in the cytosol of the cell.

Erythrocytes as an example

An example of this trigger-system in action is the process by which the formation of erythrocytes is regulated. Mammals possess this system, which begins in the kidneys where the developmental signal is manufactured. The developmental signal, also called a cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

, is erythropoietin in this case. (Cytokines are key regulators of hematopoietic cell proliferation and differentiation.) Erythropoietin's activity is initiated when hematopoietic cytokine receptors become activated. In erythrocyte regulation, erythropoietin is a protein containing 165 amino acids that plays a role in activating the cytoplasmic protein kinase JAK. The results of some newer research have also indicated that the aforementioned cytokine receptors function with members of the JAK tyrosine kinase family. The cytokine receptors activate the JAK kinases. This then results in the phosphorylation of several signaling proteins located in the cell membrane. This subsequently affects both the stimulation of ligand-mediated receptors and intracellular signaling pathway activation. Substrates for JAK kinases mediate some gene responses and more. The process is also responsible for mediating the production of blood cells. In this case, erythropoietin binds to the corresponding plasma membrane receptor, dimerizing the receptor. The dimer is responsible for activating the kinase JAK via binding. Tyrosine residues located in the cytoplasmic domain of the erythropoietin receptor are consequently phosphorylated by the activated protein kinase JAK. Overall, this is also how a receptor tyrosine kinase might be activated by a ligand to regulate erythrocyte formation.

Other examples

Additional instances of factor-influenced protein tyrosine kinase activity, similar to this one, exist. An adapter protein such as Grb2
Grb2
Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....

 will bind to phosphate-tyrosine residues under the influence of receptor protein kinases. This mechanism is an ordinary one that provokes protein-protein interactions.

Furthermore, to illustrate an extra circumstance, insulin-associated factors have been determined to influence tyrosine kinase. Insulin receptor substrate
Insulin receptor substrate
Insulin receptor substrate is an important ligand in the insulin response of human cells.IRS-1, for example, is an IRS protein which contains a phosphotyrosine binding-domain . In addition, the insulin receptor contains a NPXpY domain. The PTB-domain binds the NPXpY domain...

s are molecules that function in signaling by regulating the effects of insulin. Many receptor enzymes have closely related structure and receptor tyrosine kinase activity, and it is said by Lehninger (2008) that the foundational or prototypical receptor enzyme, is insulin. It is interesting to note that insulin receptor substrate
Insulin receptor substrate
Insulin receptor substrate is an important ligand in the insulin response of human cells.IRS-1, for example, is an IRS protein which contains a phosphotyrosine binding-domain . In addition, the insulin receptor contains a NPXpY domain. The PTB-domain binds the NPXpY domain...

s IRS2
IRS2
Insulin receptor substrate 2 is a protein that in humans is encoded by the IRS2 gene.. Mice lacking IRS2 have a diabetic phenotype as well as a 40% reduction in brain mass.-Interactions:...

 and IRS3 each have unique characteristic tissue function and distribution that serves to enhance signaling capabilities in pathways that are initiated by receptor tyrosine kinases. Activated IRS-1 molecules enhance the signal created by insulin. The insulin receptor system, in contrast, appears to diminish the efficacy of endosomal signaling.

The epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

 system, as such, has been used as an intermediate example. Some signals are produced from the actual cell surface in this case but other signals seem to emanate from within the endosome
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...

s. This variety of function may be a means to create ligand-specific signals. This supports the notion that trafficking, a term for the modification of proteins subsequent to mRNA translation, may be vital to the function of receptor signaling.

Structure

Included in a number of the structural features that can be recognized in all protein tyrosine kinases are an ATP binding site, three residues that are thought to be associated with the function of the third phosphate group (often called the gamma-phosphate group) of an ATP molecule bound to the enzyme, and a possible catalytic site of the enzyme that is an amino acid. Also very common among protein tyrosine kinases are two peptide sequences.

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....

. An example is , 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 that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....

.

Families

The tyrosine kinases are divided into two main families:
  • the transmembrane receptor-linked kinases
  • those that are cytoplasm
    Cytoplasm
    The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

    ic proteins

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
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

, 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
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 (ATP) and the substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

 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. Phosphorylation activates or deactivates many protein enzymes....

 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
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 cells.

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)
Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...

oncogenic
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...

 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 versions 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 , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. A mutation that causes certain tyrosine kinases to be constitutively active has been associated with several cancers. Imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...

 (brand names Gleevec and Glivec) is a drug able to bind the catalytic cleft of these tyrosine kinases, inhibiting its activity.

Tyrosine kinase activity is also significantly involved in other events that are sometimes considered highly unfavorable. For instance, enhanced activity of the enzyme has been implicated in the derangement of the function of certain systems, such as cell division. Also included are numerous diseases related to local inflammation such as atherosclerosis and psoriasis, or systemic inflammation such as sepsis and septic shock. A number of viruses target tyrosine kinase function during infection. The polyoma virus affects tyrosine kinase activity inside the nuclear matrix. Fibroblasts are cells involved in wound healing and cell structure formation in mammalian cells. When these cells are transformed by the polyoma virus, higher tyrosine activity is observed in the cellular matrix, which is also correlated to cellular proliferation. Another virus that targets tyrosine kinase is the Rous sarcoma virus, a retrovirus that causes sarcoma in chickens. Infected cells display obvious structure modifications and cell growth regulation that is extremely unusual. Protein tyrosine kinases that are encoded by the Rous sarcoma virus cause cellular transformation, and are termed oncoproteins. In addition, tyrosine kinase can sometimes function incorrectly in such a way that leads to non-small cell lung cancer. A common, widespread cancer, non-small cell lung cancer is the cause of death in more people than the total number in breast, colorectal, and prostate cancer together.

Research has shown that protein phosphorylation occurs on residues of tyrosine by both transmembrane receptor- and membrane-associated protein tyrosine kinases in normal cells. Phosphorylation plays a significant role in cellular signalling that regulates the number and variety of growth factors. This is evidenced by the observation that cells affected by the Rous sarcoma virus display obvious structural modifications and a total lack of normal cell growth regulation. Rous sarcoma virus-encoded oncoproteins are protein tyrosine kinases that are the cause of, and are required for, this cellular transformation. Tyrosine phosphorylation activity also increases or decreases in conjunction with changes in cell composition and growth regulation. In this way, a certain transformation exhibited by cells is dependent on a role that tyrosine kinase demonstrates. Protein tyrosine kinases, have a major role in the activation of lymphocytes. In addition, they are functional in mediating communication pathways in cell types such as adrenal chromaffin, platelets, and neural cells.

Tyrosine kinase can become a unregulated enzyme within an organism due to influences discussed, such as mutations and more. This behavior causes havoc; essential processes become disorganized. Systems on which the organism relies malfunction, resulting often in cancers. Of course, the possibility of preventing this type of circumstance is a highly desirable notion to those that are able to conduct related research. Much research has already noted the significant effect that inhibitors of the radically functioning protein tyrosine kinase enzymes have on related ailments. Encouragingly, research has been seen as quite prolific in a number of different cases.

Non-small cell lung cancer

Cancer’s response to an inhibitor of tyrosine kinase was assessed in a clinical trial. In this case, Gefitinib is the inhibitor of tyrosine kinase. Incorrect tyrosine kinase function can lead to non-small cell lung cancer. Gefitinib is a tyrosine kinase inhibitor that targets the epidermal growth factor receptor, inducing favorable outcomes in patients with non-small cell lung cancers. A common, widespread cancer, non-small cell lung cancer is the cause of death in more people than breast, colorectal, and prostate cancer together. This is strong motivation to perform research on tyrosine kinase inhibitors as potential targets in cancer treatment. Gefitinib, functioning as an epidermal growth factor receptor tyrosine kinase inhibitor, improved symptoms related to non-small cell lung cancer and resulted in radiographic tumor regressions. This is an example of the efficacy of such an inhibitor. The process of inhibition shows how the cancer sustains. Mutations in the epidermal growth factor receptor activate signalling pathways that promote cell survival. Non-small cell lung cancer cells become dependent on these survival signals. Gefitinib’s inhibition of the survival signals may be a contributing factor to its efficacy as a drug for non-small cell cancer treatment.

Gefitinib is well endured by humans, and treatment resulted in a symptom improvement rate of 43% (with 95% confidence in a 33%-53% interval) for patients that received 250 mg of Gefitinib and 35% (with 95% confidence in a 26%-45% interval) for those that received 500 mg. In the trial, epidermal growth factor receptor showed a rapid response to the inhibitor, as demonstrated by the improvement of the cancer symptoms. In each group, improvements were noted after a single week of epidermal growth factor receptor tyrosine kinase inhibitor treatment. Gefitinib application once per day caused “rapid” symptom improvement and tumor regressions in non-small cell lung cancer patients. In the field of medical research, this is an especially significant example of the use of an inhibitor to treat tyrosine kinase-associated cancer. Chemotherapy, surgery, and radiotherapy were the only major options available prior to the discoveries made in this trial. The side-effects of Gefitinib oral treatment once per day were considered significant. Diarrhea was reported in 57% of patients in the 250 mg group and in 75% of the 500 mg group. One patient had diarrhea more severe than Grade 2, with up to six bowel movements in only one day. Also, a death occurred possibly due to epidermal growth factor receptor tyrosine kinase inhibitor treatment; however, the correlation is not exactly clear. In addition, skin toxicity was observed in 62% of patients in the 250 mg group. Nevertheless the side-effects of Gefitinib were only “generally mild, manageable, noncumulative, and reversible.” Unfortunately, ceasing to take the inhibitor may be the only reversal strategy of the unfavorable symptoms. Gefitinib still represents a reasonably safe and effective treatment compared to other cancer therapies.

Furthermore, epidermal growth factor receptor plays a crucial role in tumorigenesis, which is the production of a new tumor. In the case of non-small cell lung cancer, these tumors are cancerous and dangerous to the health of a human being. Two monoclonal antibodies and another small-molecule tyrosine kinase inhibitor called Erlotinib have also been developed to treat cancer.

Chronic myeloid leukemia

BCR-ABL is a constitutively activated tyrosine kinase that is associated with chronic myeloid leukemia. It is possible that an inhibitor of tyrosine kinase could be a viable option for the treatment of BCR-ABL-caused chronic myeloid leukemia. Tyrosine kinase activity is crucial for the transformation of BCR-ABL. Therefore inhibiting it could likely improve cancer symptoms. STI571, otherwise known as CGP 57148B, is an inhibitor specific to the BCR-ABL tyrosine kinase. STI571’s efficacy was tested in 83 patients with chronic myeloid leukemia, who were administered the dose orally during the chronic phase of their ailment. These patients previously failed to respond to treatment with interferon alfa. Adverse effects of STI571 existed, but were tolerable. Nausea, myalgias, edema, and diarrhea were all negative side-effects of using STI571 to inhibit the BCR-ABL constitutively activated tyrosine kinase. A 300 mg dose of the inhibitor resulted in positive blood reactions in all but one subject within a month of the start of the treatment. Cytogenetic reactions (reactions affecting cell structure and function) were present in 29 subjects, while 17 of them demonstrated significant reactions. It is interesting to note that seven of these patients had complete recoveries from BCR-ABL-induced chronic myeloid leukemia. It was concluded that the well-tolerated inhibitor has a significant favorable effect on chromic myeloid leukemia activity in patients who failed to respond to interferon alfa treatment. The potential of tyrosine kinase inhibitor STI571 to reduce the spread of chronic myeloid leukemia further implies that the role of BCR-ABL tyrosine kinase activity in the cancer’s progression is vital. The report offers support for the creation of anticancer drugs that function according to their ability to act on the abnormalities of cancerous cells in humans.

Gastrointestinal stromal tumors

Gastrointestinal stromal tumors are known to withstand cancer chemotherapy treatment and do not respond to any kind of therapy in advanced cases. However, tyrosine kinase inhibitor STI571 is effective in the treatment of patients with metastatic gastrointestinal stromal tumors. Gastrointestinal stromal tumors consist of a cluster of mesenchymal neoplasms that are formed from precursors to cells that make up the connective-tissue in the gastrointestinal tract. Most of these tumors are found in the stomach, though they can also be located in the small intestine or elsewhere in the intestinal tract. The cells of these tumors have a growth factor receptor associated with tyrosine kinase activity. This growth factor receptor is called c-kit and is produced by a proto-oncogene (c-kit). Mutation of c-kit causes the constitutive activity of tyrosine kinase which results in cancerous gastrointestinal stromal tumors. Results of c-kit mutation include unrestricted tyrosine kinase activity and cell proliferation, unregulated phosphorylation of c-kit, and disruption of some communication pathways. Therapy with Imatinib can inhibit the non-normal cell signaling mechanisms in gastrointestinal stromal tumors. This results in significant responses in patients and sustained disease control. It is no longer doubted that this inhibitor can be effective and safe in humans. In similar manner, protein tyrosine kinase inhibitor STI571 was found to significantly reduce the physical size of tumors; they decreased roughly 65% in size in 4 months of trialing, and continued to diminish. New lesions did not appear, and a number of the liver metastases completely reduced to non-existence. The single patient in the study remained healthy following treatment. There are no effective means of treatment for advanced gastrointestinal stromal tumors, but that STI571 represents an effective treatment in early stage cancer associated with constitutively active c-kit, by inhibiting unfavourable tyrosine kinase activity

Examples

Human proteins containing this domain include:

AATK
AATK
Serine/threonine-protein kinase LMTK1 is an enzyme that in humans is encoded by the AATK gene.-Further reading:...

; ABL1; ABL2
ABL2
Tyrosine-protein kinase ABL2 also known as Abelson-related gene is an enzyme that in humans is encoded by the ABL2 gene.- Function :...

;
ALK
Anaplastic lymphoma kinase
Anaplastic lymphoma kinase also known as ALK tyrosine kinase receptor or CD246 is an enzyme that in humans is encoded by the ALK gene.-Function:...

;
AXL
AXL receptor tyrosine kinase
Tyrosine-protein kinase receptor UFO is an enzyme that in humans is encoded by the AXL gene.-Interactions:AXL receptor tyrosine kinase has been shown to interact with TENC1.-Further reading:...

;
BLK
BLK (gene)
Tyrosine-protein kinase BLK also known as B lymphocyte kinase is an enzyme that in humans is encoded by the BLK gene.-Interactions:The tyrosine-protein kinase BLK has been shown to interact with UBE3A.-Further reading:...

;
BMX
BMX (gene)
Cytoplasmic tyrosine-protein kinase BMX is an enzyme that in humans is encoded by the BMX gene.-Interactions:BMX has been shown to interact with PAK1, PTK2, PTPN21 and RUFY1.-Further reading:...

;
BTK
Bruton's tyrosine kinase
Bruton's tyrosine kinase is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia . Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor...

; CSF1R;
CSK
C-src tyrosine kinase
C-src tyrosine kinase, also known as CSK, is a human protein and gene. It includes an SH2 domain, an SH3 domain, and a tyrosine kinase domain. This protein specifically phosphorylates Tyr-504 residue on human leukocyte-specific protein tyrosine kinase, which acts as a negative regulatory site...

; DDR1
DDR1
For the older type of computer memory, see DDR SDRAM.Discoidin domain receptor family, member 1, also known as DDR1 or CD167a , is a human gene.-Further reading:...

;
DDR2;
EGFR
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

;
EPHA1
EPHA1
EPH receptor A1 is a protein that in humans is encoded by the EPHA1 gene.-Further reading:...

; EPHA2; EPHA3
EPHA3
EPH receptor A3 is a protein that in humans is encoded by the EPHA3 gene.-Interactions:EPH receptor A3 has been shown to interact with EFNB2 and EFNA5.-Further reading:...

; EPHA4; EPHA5
EPHA5
EPH receptor A5 is a protein that in humans is encoded by the EPHA5 gene.-Further reading:...

; EPHA6
EPHA6
Ephrin type-A receptor 6 is a protein that in humans is encoded by the EPHA6 gene.-Further reading:...

; EPHA7
EPHA7
Ephrin type-A receptor 7 is a protein that in humans is encoded by the EPHA7 gene.-Further reading:...

; EPHA8
EPHA8
Ephrin type-A receptor 8 is a protein that in humans is encoded by the EPHA8 gene.-Further reading:...

; EPHA10;
EPHB1; EPHB2; EPHB3
EPHB3
Ephrin type-B receptor 3 is a protein that in humans is encoded by the EPHB3 gene.-Interactions:EPHB3 has been shown to interact with MLLT4 and RAS p21 protein activator 1.-Further reading:...

; EPHB4; EPHB6
EPHB6
Ephrin type-B receptor 6 is a protein that in humans is encoded by the EPHB6 gene.-Further reading:...

; ERBB2; ERBB3
ERBB3
Receptor tyrosine-protein kinase erbB-3 is an enzyme that in humans is encoded by the ERBB3 gene.It is thought that ERBB3, when activated, becomes a substrate for dimerization and subsequent phosphorylation by ERBB1, ERBB2 and ERBB4....

; ERBB4
ERBB4
Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene. Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized....

;
FER
FER (gene)
Proto-oncogene tyrosine-protein kinase FER is an enzyme that in humans is encoded by the FER gene.-Interactions:FER has been shown to interact with TMF1 and Cortactin.-Further reading:...

;
FES
Feline sarcoma oncogene
Proto-oncogene tyrosine-protein kinase Fes/Fps is an enzyme that in humans is encoded by the FES gene.-Interactions:Feline sarcoma oncogene has been shown to interact with BCAR1 and BCR gene.-Further reading:...

;
FGFR1; FGFR2; FGFR3
FGFR3
Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the FGFR3 gene. FGFR3 has also been designated as CD333 .-Structure and function:-Disease linkage:...

; FGFR4;
FGR
FGR (gene)
Gardner-Rasheed feline sarcoma viral oncogene homolog, also known as FGR, is a protein which in humans is encoded by the FGR gene.- Function :This gene is a member of the Src family of protein tyrosine kinases...

; FLT1
FLT1
Vascular endothelial growth factor receptor 1 is a protein that in humans is encoded by the FLT1 gene.-Interactions:FLT1 has been shown to interact with PLCG1 and Vascular endothelial growth factor B.-Further reading:...

; FLT3; FLT4
FLT4
Fms-related tyrosine kinase 4, also known as FLT4, is a protein which in humans is encoded by the FLT4 gene.This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic...

;
FRK; FYN
FYN
Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...

; GSG2
GSG2
Serine/threonine-protein kinase haspin is an enzyme that in humans is encoded by the GSG2 gene.-Further reading:...

; HCK
HCK
Tyrosine-protein kinase HCK is an enzyme that in humans is encoded by the HCK gene.-Interactions:HCK has been shown to interact with BCR gene, ELMO1, Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1.-Further reading:...

; IGF1R; ILK
Ilk
Ilk is a village in Szabolcs-Szatmár-Bereg county, in the Northern Great Plain region of eastern Hungary.-Geography:It covers an area of and has a population of 1263 people ....

; INSR;
INSRR
INSRR
Insulin receptor-related protein is a protein that in humans is encoded by the INSRR gene.-Further reading:...

; IRAK4;
ITK
ITK (gene)
IL2-inducible T-cell kinase, also known as ITK, is a protein that in humans is encoded by the ITK gene.- Function :This gene encodes an intracellular tyrosine kinase expressed in T-cells...

; JAK1; JAK2; JAK3;
KDR
Kinase insert domain receptor
Kinase insert domain receptor also known as vascular endothelial growth factor receptor 2 is a VEGF receptor. KDR is the human gene encoding it. KDR has also been designated as CD309...

; KIT
CD117
Mast/stem cell growth factor receptor also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117 is a protein that in humans is encoded by the KIT gene...

; KSR1
KSR1
Kinase suppressor of Ras 1 is an enzyme that in humans is encoded by the KSR1 gene.-Further reading:...

; LCK
Lck
Lck is a protein that is found inside specialized cells of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling pathways of these lymphocytes...

; LMTK2
LMTK2
Serine/threonine-protein kinase LMTK2 also known as Lemur tyrosine kinase 2 is an enzyme that in humans is encoded by the LMTK2 gene.- Function :...

; LMTK3;
LTK; LYN
LYN
Tyrosine-protein kinase Lyn is a protein that in humans is encoded in humans by the LYN gene.Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells, in neural tissues liver, and adipose tissue. In various hematopoietic cells, Lyn has emerged...

; MATK; MERTK
MERTK
Proto-oncogene tyrosine-protein kinase MER is an enzyme that in humans is encoded by the MERTK gene.-External links:*...

; MET
C-MET
c-Met is a proto-oncogene that encodes a protein known as hepatocyte growth factor receptor . The hepatocyte growth factor receptor protein possesses tyrosine-kinase activity...

; MLTK;
MST1R
MST1R
Macrophage-stimulating protein receptor is a protein that in humans is encoded by the MST1R gene.-Further reading:...

; MUSK
MuSK protein
MuSK is a receptor tyrosine kinase required for the formation of the neuromuscular junction. It is activated by a nerve-derived proteoglycan called agrin.-MuSK is required for formation of the Neuromuscular Junction:...

; NPR1
NPR1
Natriuretic peptide receptor A/guanylate cyclase A , also known as NPR1, is an atrial natriuretic peptide receptor...

; NTRK1; NTRK2; NTRK3; PDGFRA
PDGFRA
Alpha-type platelet-derived growth factor receptor is a protein that in humans is encoded by the PDGFRA gene.-Interactions:PDGFRA has been shown to interact with PDGFRB, PLCG1, Sodium-hydrogen antiporter 3 regulator 1, Cbl gene, CRK, Caveolin 1 and PDGFC.-Further reading:...

; PDGFRB
PDGFRB
Beta-type platelet-derived growth factor receptor is a protein that in humans is encoded by the PDGFRB gene.-Interactions:PDGFRB has been shown to interact with PTPN11, NCK1, Grb2, Caveolin 1, PDGFRA, Sodium-hydrogen antiporter 3 regulator 1, RAS p21 protein activator 1, CRK, SHC1 and...

;
PLK4
PLK4
Serine/threonine-protein kinase PLK4 is an enzyme that in humans is encoded by the PLK4 gene.-Further reading:...

; PTK2
PTK2
PTK2 protein tyrosine kinase 2 , also known as Focal Adhesion Kinase , is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes...

; PTK2B
PTK2B
Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene.-Protein:-Interactions:PTK2B has been shown to interact with PTPN11, PTPN6, PITPNM1, Gelsolin, Src, GRIN2A, Ewing sarcoma breakpoint region 1, RB1CC1, TGFB1I1, NPHP1, BCAR1, FYN, DLG4, DLG3, DDEF2, Cbl gene, RAS...

; PTK6
PTK6
Tyrosine-protein kinase 6 is an enzyme that in humans is encoded by the PTK6 gene.- Function :Tyrosine-protein kinase 6 is a cytoplasmic non-receptor protein kinase which may function as an intracellular signal transducer in epithelial tissues...

; PTK7
PTK7
Tyrosine-protein kinase-like 7 is an enzyme that in humans is encoded by the PTK7 gene.-Further reading:...

;
RET
RET proto-oncogene
The RET proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signalling molecules....

; ROR1
ROR1
Tyrosine-protein kinase transmembrane receptor ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 , is an enzyme that in humans is encoded by the ROR1 gene...

; ROR2
ROR2
Tyrosine-protein kinase transmembrane receptor ROR2 also known as neurotrophic tyrosine kinase, receptor-related 2, is a protein that in humans is encoded by the ROR2 gene located on position 9 of the long arm of chromosome 9. This protein is responsible for aspects of bone and cartilage growth. It...

; ROS1; RYK; SGK493; SRC
Src (gene)
Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...

;
SRMS; STYK1
STYK1
Tyrosine-protein kinase STYK1 is an enzyme that in humans is encoded by the STYK1 gene.-Further reading:...

;
SYK
Syk
Spleen tyrosine kinase, also known as Syk, is an enyzme which in humans is encoded by the SYK gene.- Function :SYK, along with Zap-70, is a member of the Syk family of tyrosine kinases...

; TEC
TEC (gene)
Tyrosine-protein kinase Tec is an enzyme that in humans is encoded by the TEC gene.-Interactions:TEC has been shown to interact with GNA12, Janus kinase 2, CD117, Suppressor of cytokine signaling 1, ARHGEF12 and DOK1.-Further reading:...

;
TEK
TEK tyrosine kinase
Angiopoietin-1 receptor is a protein that in humans is encoded by the TEK gene.TEK has also recently been designated CD202B .-Interactions:...

; TEX14; TIE1
TIE1
Tyrosine kinase with immunoglobulin-like and EGF-like domains 1 also known as TIE1 is an angiopoietin receptor which in humans is encoded by the TIE1 gene.- Function :...

; TNK1; TNK2
TNK2
Activated CDC42 kinase 1 is an enzyme that in humans is encoded by the TNK2 gene.-Interactions:TNK2 has been shown to interact with FYN and Grb2.-Further reading:...

; TNNI3K; TXK
TXK (gene)
Tyrosine-protein kinase TXK is an enzyme that in humans is encoded by the TXK gene.-Further reading:...

;
TYK2; TYRO3
TYRO3
Tyrosine-protein kinase receptor TYRO3 is an enzyme that in humans is encoded by the TYRO3 gene.-Interactions:TYRO3 has been shown to interact with PIK3R1 and GAS6.-Further reading:...

; YES1
YES1
Proto-oncogene tyrosine-protein kinase Yes is an enzyme that in humans is encoded by the YES1 gene.-Interactions:YES1 has been shown to interact with Janus kinase 2, CTNND1, RPL10 and Occludin.-Further reading:...

; ZAP70

External links

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