Phospholipase D
Encyclopedia
Phospholipase D is an enzyme
which is located in the plasma membrane and catalyzes the hydrolysis of phosphatidylcholine
to form phosphatidic acid
(PA), releasing the soluble choline
headgroup into the cytosol. There are two mammalian isoforms of phospholipase D: PLD1 and PLD2
.
, ERK
, TYK and controls the signalling indicating that PLD is activated by these kinases. As choline is very abundant in the cell, PLD activity does not significantly affect choline levels, and choline is unlikely to play any role in signalling.
Phosphatidic acid is a signal molecule and acts to recruit SK1
to membranes. PA is extremely short lived and is rapidly hydrolysed
by the enzyme PA phosphohydrolase to form diacylglycerol
(DAG). DAG may also be converted to PA by DAG kinase
. Although PA and DAG are interconvertible, they do not act in the same pathways. Stimuli that activate PLD do not activate enzymes downstream of DAG and vice versa.
It is possible that, though PA and DAG are interconvertible, separate pools of signalling and non-signalling lipids may be maintained. Studies have suggested that DAG signalling is mediated by polyunsaturated DAG while PLD derived PA is monounsaturated or saturated. Thus functional saturated/monounsaturated PA can be degraded by hydrolysing it to form non-functional saturated/monounsaturated DAG while functional polyunsaturated DAG can be degraded by converting it into non-functional polyunsaturated PA.
Finally, a lysophospholipase D called autotaxin
was recently identified as having an important role in cell-proliferation through its product,
lysophosphatidic acid
(LPA).
endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs.
Human proteins containing this motif include:
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
which is located in the plasma membrane and catalyzes the hydrolysis of phosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines 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 soy beans from which they are mechanically extracted or chemically...
to form phosphatidic acid
Phosphatidate
Phosphatidic acids are the acid forms of phosphatidates, a part of common phospholipids, major constituents of cell membranes. Phosphatidic acids are the simplest diacyl-glycerophospholipids.-Structure:...
(PA), releasing the soluble choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
headgroup into the cytosol. There are two mammalian isoforms of phospholipase D: PLD1 and PLD2
PLD2
Phospholipase D2 is an enzyme that in humans is encoded by the PLD2 gene.-Interactions:PLD2 has been shown to interact with BIN1, Amphiphysin, Aldolase A, PLCG1, ARF1, Src, PRKCD, Glyceraldehyde 3-phosphate dehydrogenase ,Caveolin 1,and Wiskott-Aldrich syndrome protein.-Inhibitors:* N--2-naphthamide:...
.
Function
Mammalian PLD directly interacts with kinases like PKCProtein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
, ERK
Extracellular signal-regulated kinases
In molecular biology, extracellular-signal-regulated kinases or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells...
, TYK and controls the signalling indicating that PLD is activated by these kinases. As choline is very abundant in the cell, PLD activity does not significantly affect choline levels, and choline is unlikely to play any role in signalling.
Phosphatidic acid is a signal molecule and acts to recruit SK1
Sphingosine kinase 1
Sphingosine kinase 1 is an enzyme that in humans is encoded by the SPHK1 gene.Sphingosine kinase 1 phosphorylates sphingosine to sphingosine-1-phosphate SK1 is normally a cytosolic protein but is recruited to membranes rich in phosphatidate , a product of Phospholipase D Sphingosine-1-phosphate ...
to membranes. PA is extremely short lived and is rapidly hydrolysed
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
by the enzyme PA phosphohydrolase to form diacylglycerol
Diglyceride
A diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages....
(DAG). DAG may also be converted to PA by DAG kinase
Diacylglycerol kinase
Diacylglycerol kinase is a family of enzymes that catalyzes the conversion of diacylglycerol to phosphatidic acid utilizing ATP as a source of the phosphate...
. Although PA and DAG are interconvertible, they do not act in the same pathways. Stimuli that activate PLD do not activate enzymes downstream of DAG and vice versa.
It is possible that, though PA and DAG are interconvertible, separate pools of signalling and non-signalling lipids may be maintained. Studies have suggested that DAG signalling is mediated by polyunsaturated DAG while PLD derived PA is monounsaturated or saturated. Thus functional saturated/monounsaturated PA can be degraded by hydrolysing it to form non-functional saturated/monounsaturated DAG while functional polyunsaturated DAG can be degraded by converting it into non-functional polyunsaturated PA.
Finally, a lysophospholipase D called autotaxin
Autotaxin
Autotaxin also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2 is an enzyme that in humans is encoded by the ENPP2 gene.- Function :...
was recently identified as having an important role in cell-proliferation through its product,
lysophosphatidic acid
Lysophosphatidic acid
Lysophosphatidic acid is a phospholipid derivative that can act as a signaling molecule.-Function:LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPA1, LPA2, and LPA3...
(LPA).
Isoforms
Human proteins possessing phospholipase D activity include:Active site motif
Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolyzing PLD is a homologue of cardiolipin synthase,, phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, and/or asparagine residues which may contribute to the active site aspartic acid. An Escherichia coliEscherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs.
Human proteins containing this motif include:
- PGS1, PLD1, PLD2PLD2Phospholipase D2 is an enzyme that in humans is encoded by the PLD2 gene.-Interactions:PLD2 has been shown to interact with BIN1, Amphiphysin, Aldolase A, PLCG1, ARF1, Src, PRKCD, Glyceraldehyde 3-phosphate dehydrogenase ,Caveolin 1,and Wiskott-Aldrich syndrome protein.-Inhibitors:* N--2-naphthamide:...
, PLD3, PLD4, PLD5