Editing Tyrosine kinase (section)

== Families ==
There are 90 human genes that contain a total of 94 protein tyrosine kinase domains (PTKs). Four genes contain both a catalytically active kinase domain and a [[pseudokinase domain]] (a kinase domain with no catalytic activity: [[JAK1]], [[JAK2]], [[JAK3]], and [[TYK2]]). Including these four genes, there are 82 human genes that contain a catalytically active tyrosine kinase domain They are divided into two classes, receptor and non-receptor tyrosine kinases.

===Receptor===
{{further|Receptor tyrosine kinase}}
By 2004, 58 human [[receptor tyrosine kinases]] (RTKs) were known, grouped into 20 subfamilies. Eight of these membrane proteins which contain tyrosine protein kinase domains are actually pseudokinases, without catalytic activity ([[EPHA10]], [[EPHB6]], [[ERBB3]], [[PTK7]], [[ROR1]], [[ROR2]], [[Related to receptor tyrosine kinase|RYK]], and [[STYK1]]). Receptor tyrosine kinases play pivotal roles in diverse cellular activities including growth (by signaling neurotrophins), [[Cellular differentiation|differentiation]], metabolism, adhesion, motility, and death.<ref>{{cite journal | vauthors = Bhise SB, Nalawade AD, Wadhawa H | title = Role of protein tyrosine kinase inhibitors in cancer therapeutics | journal = Indian Journal of Biochemistry & Biophysics | volume = 41 | issue = 6 | pages = 273–280 | date = December 2004 | pmid = 22900354 | url = http://nopr.niscair.res.in/handle/123456789/33808 | archive-date = 2017-02-12 | access-date = 2017-02-11 | archive-url = https://web.archive.org/web/20170212090927/http://nopr.niscair.res.in/handle/123456789/33808 | url-status = live }}</ref>
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 (biochemistry)|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,<ref name="pmid18045055">{{cite journal | vauthors = Gunby RH, Sala E, Tartari CJ, Puttini M, Gambacorti-Passerini C, Mologni L | title = Oncogenic fusion tyrosine kinases as molecular targets for anti-cancer therapy | journal = Anti-Cancer Agents in Medicinal Chemistry | volume = 7 | issue = 6 | pages = 594–611 | date = November 2007 | pmid = 18045055 | doi = 10.2174/187152007784111340 }}</ref> 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===
{{further|Non-receptor tyrosine kinase}}
In humans, there are 32 cytoplasmic protein tyrosine kinases ({{EC number|2.7.10.2}}).

The first non-receptor tyrosine kinase identified was the ''[[Src (gene)|v-src]]'' [[Oncogene|oncogenic]] protein. Most animal cells contain one or more members of the ''Src'' family of tyrosine kinases. A [[chicken sarcoma virus]], the Rous sarcoma virus mentioned above, was found to carry mutated versions of the normal cellular Src gene.<ref>{{cite news |last1=Tontonoz |first1=Matthew |title=How a Chicken Helped Solve the Mystery of Cancer |url=https://www.mskcc.org/news/how-chicken-helped-solve-mystery |access-date=27 October 2022 |publisher=Memorial Sloan Kettering Cancer Center |date=December 27, 2017 |archive-date=27 October 2022 |archive-url=https://web.archive.org/web/20221027020255/https://www.mskcc.org/news/how-chicken-helped-solve-mystery |url-status=live }}</ref> 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''.{{citation needed|date=February 2016}}