Phospholipase D2 is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''PLD2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
Phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can easily be obtained from a variety of readily available sources, such as egg yolk or soyb ...
(PC)-specific
phospholipases D (PLDs) catalyze the hydrolysis of PC to produce
phosphatidic acid and
choline. Activation of PC-specific PLDs occurs as a consequence of agonist stimulation of both
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
and
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...
s. PC-specific PLDs have been proposed to function in regulated secretion, cytoskeletal reorganization, transcriptional regulation, and cell cycle control.
upplied by OMIMref name="entrez">
Mechanism of activation
PLD2 is activated by
substrate presentation.
The enzyme is palmitoylated, which drives PLD2 to lipid rafts. PC substrate is polyunsaturated and resides in the membrane separately from lipid rafts near phosphatidylinositol 4,5-bisphosphate (PIP2). When PIP2 levels increase, PLD2 trafficks to PIP2 where it encounters its substrate PC. Scaffolding proteins that interact with PLD2 likely changes its preference of lipid rafts vs PIP2.
Interactions
PLD2 has been shown to
interact with:
*
ARF1,
*
Aldolase A,
*
Amphiphysin,
[
* BIN1,]Glyceraldehyde 3-phosphate dehydrogenase
Glyceraldehyde 3-phosphate dehydrogenase (abbreviated GAPDH) () is an enzyme of about 37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long establis ...
,PRKCD
Protein kinase C delta type (or PKC-δ) is an enzyme that in humans is encoded by the ''PRKCD'' gene.
Function
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second messeng ...
,
Inhibitors
* ''N''-(2-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro .5ecan-8-yl)ethyl)-2-naphthamide: 75-fold selective versus PLD1, IC50 = 20 nM.
References
Further reading
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EC 3.1.4