Phospholipase D2 is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that in humans is encoded by the ''PLD2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

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 soybea ...

(PC)-specific phospholipases D (PLDs) catalyze the hydrolysis of PC to produce

phosphatidic acid Phosphatidic 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 ac ...

and

choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but r ...

. 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 p ...

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 Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...

with: * ARF1, *

Aldolase A Aldolase A (ALDOA, or ALDA), also known as fructose-bisphosphate aldolase, is an enzyme that in humans is encoded by the ''ALDOA'' gene on chromosome 16. The protein encoded by this gene is a glycolytic enzyme that catalyzes the reversible conve ...

, *

Amphiphysin Amphiphysin is a protein that in humans is encoded by the ''AMPH'' gene. Function This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff person syndrome who were also affected ...

, * BIN1, *

Caveolin 1 Caveolin-1 is a protein that in humans is encoded by the ''CAV1'' gene. Function The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits ...

, *

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 establishe ...

, *

PLCG1 Phospholipase C, gamma 1, also known as PLCG1,is a protein that in humans involved in cell growth, migration, apoptosis, and proliferation. It is encoded by the ''PLCG1'' gene and is part of the PLC superfamily. Function PLCγ1 is a cell grow ...

, *

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 messe ...

, * Src, and * Wiskott-Aldrich syndrome protein.

Inhibitors

* ''N''-(2-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro .5ecan-8-yl)ethyl)-2-naphthamide: 75-fold selective versus

PLD1 Phospholipase D1 (PLD1) is an enzyme that in humans is encoded by the ''PLD1'' gene, though analogues are found in plants, fungi, prokaryotes, and even viruses. History The possibility of PLD1 was first mentioned in 1947 by authors Hanahan and C ...

, IC₅₀ = 20 nM.

Function

Mechanism of activation

Interactions

Inhibitors

References

Further reading