Diacylglycerol kinase
Encyclopedia
Diacylglycerol kinase (DGK or DAGK) is a family of enzymes that catalyzes the conversion of diacylglycerol
(DAG) to phosphatidic acid (PA) utilizing ATP
as a source of the phosphate. In non-stimulated cells, DGK activity is low allowing DAG to be used for glycerophospholipid
biosynthesis but on receptor activation of the phosphoinositide pathway, DGK activity increases driving the conversion of DAG to PA. As both lipids are thought to function as bioactive lipid signaling
molecules with distinct cellular targets, DGK therefore occupies an important position, effectively serving as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another.
In bacteria
, DGK is very small (13 to 15 kD) membrane protein
which seems to contain three transmembrane domains. The best conserved
region, is a stretch of 12 residues
which are located in a cytoplasm
ic loop between the second and third transmembrane domains. Some Gram-positive bacteria also encode a soluble diacylglycerol kinase capable of reintroducing DAG into the phospholipid
biosynthesis pathway. DAG accumulates in Gram-positive bacteria as a result of the transfer of glycerol-1-phosphate moieties from phosphatidylglycerol
to lipotechoic acid .
rich domains, they are further classified into five groups according to the presence of additional functional domains and substrate specificity. These are as follows:
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) to phosphatidic acid (PA) utilizing ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
as a source of the phosphate. In non-stimulated cells, DGK activity is low allowing DAG to be used for glycerophospholipid
Glycerophospholipid
Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes.-Structures:...
biosynthesis but on receptor activation of the phosphoinositide pathway, DGK activity increases driving the conversion of DAG to PA. As both lipids are thought to function as bioactive lipid signaling
Lipid signaling
Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses...
molecules with distinct cellular targets, DGK therefore occupies an important position, effectively serving as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another.
In bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, DGK is very small (13 to 15 kD) membrane protein
Membrane protein
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...
which seems to contain three transmembrane domains. The best conserved
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
region, is a stretch of 12 residues
Residue (chemistry)
In chemistry, residue is the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction....
which are located in a cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic loop between the second and third transmembrane domains. Some Gram-positive bacteria also encode a soluble diacylglycerol kinase capable of reintroducing DAG into the phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
biosynthesis pathway. DAG accumulates in Gram-positive bacteria as a result of the transfer of glycerol-1-phosphate moieties from phosphatidylglycerol
Phosphatidylglycerol
Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant.The general structure of phosphatidylglycerol consists of a L-glycerol 3-phosphate backbone ester-bonded to either saturated or unsaturated fatty acids on carbons 1 and 2. The head group substituent glycerol is bonded...
to lipotechoic acid .
DGK Isoforms
Currently, nine members of the DGK family have been cloned and identified. Although all family members have conserved catalytic domains and two cysteineCysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
rich domains, they are further classified into five groups according to the presence of additional functional domains and substrate specificity. These are as follows:
- Type 1 - DGK-α, DGK-β, DGK-γ - contain EF-hand motifs and a recoverin homology domain
- Type 2 - DGK-δ, DGK-η - contain a pleckstrin homology domain
- Type 3 - DGK-ε - has specificity for arachidonate-containing DAG
- Type 4 - DGK-ζ, DGK-ι - contain a MARCKS homology domain, ankyrinAnkyrinAnkyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane skeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins...
repeats and a nuclear localisation signal - Type 5 - DGK-θ - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region