PLD2
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Phospholipase D2 is an
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates int ...

enzyme
that in humans is encoded by the ''PLD2''
gene In biology, a gene (from ''genos'' "...Wilhelm Johannsen coined the word gene to describe the Mendelian_inheritance#History, Mendelian units of heredity..." (Greek language, Greek) meaning ''generation'' or ''birth'' ) is a basic unit of her ...

gene
.


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 be easily obtained from a variety of readily available sources, such as egg yolk or soybeans, ...

Phosphatidylcholine
(PC)-specific phospholipases D (PLDs) catalyze the hydrolysis of PC to produce
phosphatidic acidPhosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty aci ...

phosphatidic acid
and
choline Choline is an essential nutrient A nutrient is a substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of attributes * Chemical substance, a material with a definite chemical composition * ...

choline
. Activation of PC-specific PLDs occurs as a consequence of agonist stimulation of both
tyrosine kinase A tyrosine kinase is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the e ...

tyrosine kinase
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 prot ...
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 presentationSubstrate presentation is a biological process that activates a protein. The protein is sequestered away from its substrate and then activated by release and exposure of the protein to its substrate. A Substrate (chemistry), substrate is typically th ...
. 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 Interact may refer to: * Interaction Interaction is a kind of action that occurs as two or more objects have an effect upon one another. The idea of a two-way effect is essential in the concept of interaction, as opposed to a one-way causal ef ...
with: *
ARF1 ADP-ribosylation factor 1 is a protein that in humans is encoded by the ''ARF1'' gene. Function ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that s ...
, *
Aldolase A Aldolase A (ALDOA, or ALDA), also known as fructose-bisphosphate aldolase, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act ...
, *
Amphiphysin Amphiphysin is a protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme cata ...
, *
BIN1 Myc box-dependent-interacting protein 1, also known as Bridging Integrator-1 and Amphiphysin-2 is a protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), res ...

BIN1
, *
Caveolin 1 Caveolin-1 is a protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme ...
, * Glyceraldehyde 3-phosphate dehydrogenase, * PLCG1, * PRKCD, * Src (gene), Src, and * Wiskott-Aldrich syndrome protein.


Inhibitors

* ''N''-(2-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)-2-naphthamide: 75-fold selective versus Phospholipase D1, PLD1, IC50 = 20 nM.


References


Further reading

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