Editing Kinase (section)

==Lipid kinases==
Lipid kinases phosphorylate lipids in the cell, both on the plasma membrane as well as on the membranes of the organelles. The addition of phosphate groups can change the reactivity and localization of the lipid and can be used in signal transmission.

===Phosphatidylinositol kinases===
{{See also|Phosphatidylinositol phosphate kinases}}
[[File:PI3 Kinase.tif|thumb|upright=1|Insulin binding to its receptor leads allows PI3 kinase to dock at the membrane where it can phosphorylate PI lipids]]
Phosphatidylinositol kinases phosphorylate [[phosphatidylinositol]] species, to create species such as [[phosphatidylinositol 3,4-bisphosphate]] (PI(3,4)P<sub>2</sub>), [[phosphatidylinositol 3,4,5-trisphosphate]] (PIP<sub>3</sub>), and [[phosphatidylinositol 3-phosphate]] (PI3P). The kinases include [[phosphoinositide 3-kinase]] (PI3K), [[phosphatidylinositol-4-phosphate 3-kinase]], and [[phosphatidylinositol-4,5-bisphosphate 3-kinase]]. The phosphorylation state of phosphatidylinositol plays a major role in [[cellular signalling]], such as in the insulin signalling pathway, and also has roles in [[endocytosis]], [[exocytosis]] and other trafficking events.<ref>{{cite journal | vauthors = Sun Y, Thapa N, Hedman AC, Anderson RA | title = Phosphatidylinositol 4,5-bisphosphate: targeted production and signaling | journal = BioEssays | volume = 35 | issue = 6 | pages = 513–522 | date = June 2013 | pmid = 23575577 | pmc = 3882169 | doi = 10.1002/bies.201200171 }}</ref><ref>{{cite journal | vauthors = Heath CM, Stahl PD, Barbieri MA | title = Lipid kinases play crucial and multiple roles in membrane trafficking and signaling | journal = Histology and Histopathology | volume = 18 | issue = 3 | pages = 989–998 | date = July 2003 | pmid = 12792909 | doi = 10.14670/HH-18.989 }}</ref> Mutations in these kinases, such as PI3K, can lead to [[cancer]] or [[insulin resistance]].<ref>{{cite journal| vauthors = Cantley LC |title=PI 3-kinase and disease|journal=BMC Proceedings|year=2012|volume=6|issue=Suppl 3|pages=O2|doi=10.1186/1753-6561-6-S3-O2 |pmc=3395034 |doi-access=free}}</ref>

The kinase enzymes increase the rate of the reactions by making the inositol hydroxyl group more nucleophilic, often using the side chain of an amino acid residue to act as a general base and [[deprotonate]] the hydroxyl, as seen in the mechanism below.<ref name="PI" /> Here, a reaction between [[adenosine triphosphate|adenosine triphosphate (ATP)]] and phosphatidylinositol is coordinated. The end result is a phosphatidylinositol-3-phosphate as well as [[adenosine diphosphate|adenosine diphosphate (ADP)]]. The enzymes can also help to properly orient the ATP molecule, as well as the inositol group, to make the reaction proceed faster. Metal ions are often coordinated for this purpose.<ref name="PI" />

[[File:PI3kinase mechanism.png|thumb|upright=2.7|center|Mechanism of phosphatidylinositol-3 kinase. ATP and phosphatidylinositol react to form phosphatidylinositol-3-phosphate and ADP, with the help of general base ''B''.<ref name="PI">{{cite journal | vauthors = Miller S, Tavshanjian B, Oleksy A, Perisic O, Houseman BT, Shokat KM, Williams RL | title = Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34 | journal = Science | volume = 327 | issue = 5973 | pages = 1638–1642 | date = March 2010 | pmid = 20339072 | pmc = 2860105 | doi = 10.1126/science.1184429 | bibcode = 2010Sci...327.1638M }}</ref>]]

===Sphingosine kinases===
Sphingosine kinase (SK) is a lipid kinase that catalyzes the conversion of [[sphingosine]] to [[sphingosine-1-phosphate]] (S1P). Sphingolipids are ubiquitous membrane lipids. Upon activation, sphingosine kinase migrates from the cytosol to the plasma membrane where it transfers a γ phosphate (which is the last or terminal phosphate) from [[Adenosine triphosphate|ATP]] or [[Guanosine triphosphate|GTP]] to sphingosine. The S1P receptor is a [[GPCR]] receptor, so S1P has the ability to regulate G protein signaling. The resulting signal can activate intracellular effectors like ERKs, [[Rho family of GTPases|Rho GTPase]], [[Rac (GTPase)|Rac GTPase]], [[phospholipase C|PLC]], and AKT/PI3K. It can also exert its effect on target molecules inside the cell. S1P has been shown to directly inhibit the histone deacetylase activity of [[HDAC]]s. In contrast, the dephosphorylated sphingosine promotes cell [[apoptosis]], and it is therefore critical to understand the regulation of SKs because of its role in determining cell fate. Past research shows that SKs may sustain cancer cell growth because they promote cellular-proliferation, and SK1 (a specific type of SK) is present at higher concentrations in certain types of cancers.

There are two kinases present in mammalian cells, SK1 and SK2. SK1 is more specific compared to SK2, and their expression patterns differ as well. SK1 is expressed in lung, spleen, and leukocyte cells, whereas SK2 is expressed in kidney and liver cells. The involvement of these two kinases in cell survival, proliferation, differentiation, and [[inflammation]] makes them viable candidates for [[chemotherapy|chemotherapeutic therapies]].<ref>{{cite journal | vauthors = Neubauer HA, Pitson SM | title = Roles, regulation and inhibitors of sphingosine kinase 2 | journal = The FEBS Journal | volume = 280 | issue = 21 | pages = 5317–5336 | date = November 2013 | pmid = 23638983 | doi = 10.1111/febs.12314 | doi-access = free }}</ref>