Editing Tyrosine kinase (section)

== 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.<ref name="Lehninger_2008"/> Although more research indicates 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 were researched.<ref name="Wiley_2001">{{cite journal | vauthors = Wiley HS, Burke PM | title = Regulation of receptor tyrosine kinase signaling by endocytic trafficking | journal = Traffic | volume = 2 | issue = 1 | pages = 12–18 | date = January 2001 | pmid = 11208164 | doi = 10.1034/j.1600-0854.2001.020103.x | s2cid = 7329602 | doi-access = free }}</ref> In addition, ligands participate in reversible binding, with inhibitors binding 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.<ref name="Rinker_2008">{{cite journal | vauthors = Rinker S, Ke Y, Liu Y, Chhabra R, Yan H | title = Self-assembled DNA nanostructures for distance-dependent multivalent ligand-protein binding | journal = Nature Nanotechnology | volume = 3 | issue = 7 | pages = 418–422 | date = July 2008 | pmid = 18654566 | pmc = 2556356 | doi = 10.1038/nnano.2008.164 }}</ref> 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.<ref name="Lehninger_2008"/> 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.<ref name="Lehninger_2008"/>

===Erythrocytes===
An example of this trigger-system in action is the process by which the formation of [[erythrocyte]]s is regulated. Mammals possess this system, which begins in the kidneys where the developmental signal is manufactured.<ref name="Lehninger_2008"/> The developmental signal, also called a [[cytokine]], 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.<ref name="Silvennoinen_1997">{{cite journal | vauthors = Silvennoinen O, Saharinen P, Paukku K, Takaluoma K, Kovanen P | title = Cytokine receptor signal transduction through Jak tyrosine kinases and Stat transcription factors | journal = APMIS | volume = 105 | issue = 7 | pages = 497–509 | date = July 1997 | pmid = 9269296 | doi = 10.1111/j.1699-0463.1997.tb05047.x | s2cid = 21902484 }}</ref> In erythrocyte regulation, erythropoietin is a protein containing 165 amino acids that plays a role in activating the cytoplasmic protein kinase JAK.<ref name="Lehninger_2008"/>  The results of some newer research have also indicated that the aforementioned cytokine receptors function with members of the [[Janus kinase|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.<ref name="Silvennoinen_1997"/> Substrates for JAK kinases mediate some gene responses and more.<ref name="Silvennoinen_1997"/> The process is also responsible for mediating the production of blood cells.<ref name="Lehninger_2008"/> In this case, erythropoietin binds to the corresponding plasma membrane receptor, dimerizing the receptor.<ref name="Lehninger_2008"/> The dimer is responsible for activating the kinase JAK via binding.<ref name="Lehninger_2008"/> Tyrosine residues located in the cytoplasmic domain of the erythropoietin receptor are consequently phosphorylated by the activated protein kinase JAK.<ref name="Lehninger_2008"/> Overall, this is also how a receptor tyrosine kinase might be activated by a ligand to regulate erythrocyte formation.{{citation needed|date=April 2022}}

===Other examples===
Additional instances of factor-influenced protein tyrosine kinase activity, similar to this one, exist. An adapter protein such as [[Grb2]] will bind to phosphate-tyrosine residues under the influence of receptor protein kinases. This mechanism is an ordinary one that provokes protein-protein interactions.<ref name="Lehninger_2008"/>

Furthermore, to illustrate an extra circumstance, insulin-associated factors have been determined to influence tyrosine kinase. [[Insulin receptor substrate]]s are molecules that function in signaling by regulating the effects of insulin.<ref name="Lehninger_2008"/> Many receptor enzymes have closely related structure and receptor tyrosine kinase activity, and it has been determined that the foundational or prototypical receptor enzyme is insulin.<ref name="Lehninger_2008"/> Insulin receptor substrates [[IRS2]] 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.<ref name="Lehninger_2008"/> Activated [[IRS-1]] molecules ''enhance'' the signal created by insulin.<ref name="Lehninger_2008"/> The insulin receptor system, in contrast, appears to ''diminish'' the efficacy of endosomal signaling.<ref name="Wiley_2001"/>

The [[epidermal growth factor receptor]] system, as such, has been used as an intermediate example.<ref name="Wiley_2001"/> Some signals are produced from the actual cell surface in this case but other signals seem to emanate from within the [[endosome]]s. This variety of function may be a means to create ligand-specific signals.<ref name="Wiley_2001"/> 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.

<gallery>
Image:L-tyrosine-skeletal.png|[[Tyrosine]]
Image:Phosphate Group.svg|[[Phosphate]]
Image:ATP structure revised.svg|[[Adenosine triphosphate|ATP]]
</gallery>