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Information on EC 2.7.1.107 - diacylglycerol kinase (ATP) and Organism(s) Mus musculus and UniProt Accession Q9R1C6
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2.7.1.107 diacylglycerol kinase (ATP)IUBMB Comments
Involved in synthesis of membrane phospholipids and the neutral lipid triacylglycerol. Activity is stimulated by certain phospholipids [4,7]. In plants and animals the product 1,2-diacyl-sn-glycerol 3-phosphate is an important second messenger. cf. EC 2.7.1.174, diacylglycerol kinase (CTP).
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Word Map
- 2.7.1.107
-
phosphatidic
- phospholipase
- phospholipid
- pkc
- phosphatidylinositol
-
phorbol
- isozymes
- phosphoinositide
- phosphatidylcholine
- inositol
- ceramide
- lipase
-
arachidonic
- deoxyguanosine
- deoxycytidine
-
ef-hands
- phosphatidylserine
- 13-acetate
-
polyphosphoinositide
-
phosphohydrolase
-
prelabeled
- deoxynucleoside
- staurosporine
- sphingosine
- pip2
-
pleckstrin
- 4,5-bisphosphate
-
1,4,5-trisphosphate
- 4-phosphate
- deoxyribonucleoside
- analysis
- marcks
-
kinase-dead
- medicine
- phosphatidylethanol
-
transphosphatidylation
- dioctanoylglycerol
- hypospadias
- ptdoh
- 5-kinase
- agriculture
-
3hglycerol
- monoacylglycerols
-
anergy
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
dgk, diacylglycerol kinase, dag kinase, dg kinase, dgkzeta, dagk, dgkalpha, dgk-zeta, diglyceride kinase, dgkepsilon, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DGKepsilon
1,2-diacylglycerol kinase
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-
-
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adenosine 5'-triphosphate:1,2-diacylglycerol 3-phosphotransferase
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-
-
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arachidonoyl-specific diacylglycerol kinase
-
-
-
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ATP:diacylglycerol phosphotransferase
-
-
-
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DAGK
-
-
-
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DAGKalpha
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-
-
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DG kinase
-
-
-
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DGK
-
-
-
-
DGK-alpha
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-
-
-
DGK-theta
DGKbeta
-
-
-
-
DGKdelta
DGKgamma
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-
-
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DGKiota
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-
-
-
DGKksi
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-
-
-
DGKzeta
diacylglycerol kinase
-
-
-
-
diacylglycerol kinase (ATP dependent)
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-
-
-
diacylglycerol kinase delta
diacylglycerol kinase zeta
diacylglycerol kinase-zeta
diacylglycerol:ATP kinase
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-
-
-
diglyceride kinase
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-
-
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kinase (phosphorylating), 1,2-diacylglycerol
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-
-
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kinase, 1,2-diacylglycerol (phosphorylating)
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-
-
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sn-1,2-diacylglycerol kinase
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-
-
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DGK-theta
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-
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DGKdelta
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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-
-
-
PATHWAY SOURCE
PATHWAYS
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-, -
SYSTEMATIC NAME
IUBMB Comments
ATP:1,2-diacyl-sn-glycerol 3-phosphotransferase
Involved in synthesis of membrane phospholipids and the neutral lipid triacylglycerol. Activity is stimulated by certain phospholipids [4,7]. In plants and animals the product 1,2-diacyl-sn-glycerol 3-phosphate is an important second messenger. cf. EC 2.7.1.174, diacylglycerol kinase (CTP).
CAS REGISTRY NUMBER
COMMENTARY
60382-71-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
DGKepsilon exhibits specificity for diacylglcerol substrates containing an arachidonoyl chain in the sn-2 position
-
-
?
ATP + 1,2-dipalmitoyl-sn-glycerol
ADP + 1,2-dipalmitoyl-sn-glycerol 3-phosphate
preferred substrate for isoform DGKzeta
-
-
?
ATP + 1-palmitoyl-2-oleoyl-sn-glycerol
ADP + 1-palmitoyl-2-oleoyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
DAGKalpha is stimulated vby Src-like kinase-dependent phosphoinositide 3 kinase activation in lymphocytes. In vivo the increase in cellular levels of Src-like kinase-dependent phosphoinositide 3 kinase products is sufficient to induce DAGKalpha activation, allowing DAGKalpha relocation to the intact lymphocyte
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
high level expression of DGKalpha is induced following a signal transmitted through the pre-T-cell-receptor and the protein tyrosine kinase lck. Activity of DGKalpha contributes to survival in CD4+ 8+ double positive thymocytes as pharmacological inhibition of DGK activity results in death of this cell population both in cell suspension and thymic explants. DGKalpha promotes survival in theses thymocytes through a Bcl-regulated pathway
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
1,2-diacyl-sn-glycerol 3-phosphate is phosphatidic acid
-
ir
additional information
?
-
-
diacylglycerol kinase delta regulates protein kinase C and epidermal growth factor receptor signaling
-
-
?
additional information
?
-
-
diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii
-
-
?
additional information
?
-
diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii
-
-
?
additional information
?
-
-
nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
-
-
?
additional information
?
-
nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
-
-
?
additional information
?
-
-
T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha
-
-
?
additional information
?
-
activation of a Ca2+-independent protein kinase C isozyme by 1,2-diacylglycerol, which is generated by phospholipase Cbeta and phospholipase D activation and inactivated by phosphorylation via diacylglycerol kinase, is responsible for the endothelin-1-induced decreases in Ca2+ transients and cell shortening
-
-
?
additional information
?
-
-
activation of a Ca2+-independent protein kinase C isozyme by 1,2-diacylglycerol, which is generated by phospholipase Cbeta and phospholipase D activation and inactivated by phosphorylation via diacylglycerol kinase, is responsible for the endothelin-1-induced decreases in Ca2+ transients and cell shortening
-
-
?
additional information
?
-
diacylglycerol kinase zeta and syntrophins play a role at multiple stages of the cell fusion process. Potential link between changes in the lipid content of the membranebilayer and reorganization of the actin cytoskeleton during myoblast fusion
-
-
?
additional information
?
-
-
diacylglycerol kinase zeta is a key determinant of cell cycle progression and differentiation of C2C12 cells
-
-
?
additional information
?
-
diacylglycerol kinase zeta is a key determinant of cell cycle progression and differentiation of C2C12 cells
-
-
?
additional information
?
-
-
diacylglycerol kinases alpha and zeta synergistically promote T cell maturation in the thymus
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-dipalmitoyl-sn-glycerol
ADP + 1,2-dipalmitoyl-sn-glycerol 3-phosphate
preferred substrate for isoform DGKzeta
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
DAGKalpha is stimulated vby Src-like kinase-dependent phosphoinositide 3 kinase activation in lymphocytes. In vivo the increase in cellular levels of Src-like kinase-dependent phosphoinositide 3 kinase products is sufficient to induce DAGKalpha activation, allowing DAGKalpha relocation to the intact lymphocyte
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
-
high level expression of DGKalpha is induced following a signal transmitted through the pre-T-cell-receptor and the protein tyrosine kinase lck. Activity of DGKalpha contributes to survival in CD4+ 8+ double positive thymocytes as pharmacological inhibition of DGK activity results in death of this cell population both in cell suspension and thymic explants. DGKalpha promotes survival in theses thymocytes through a Bcl-regulated pathway
-
-
?
additional information
?
-
-
diacylglycerol kinase delta regulates protein kinase C and epidermal growth factor receptor signaling
-
-
?
additional information
?
-
-
diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii
-
-
?
additional information
?
-
diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii
-
-
?
additional information
?
-
-
nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
-
-
?
additional information
?
-
nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
-
-
?
additional information
?
-
-
T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha
-
-
?
additional information
?
-
activation of a Ca2+-independent protein kinase C isozyme by 1,2-diacylglycerol, which is generated by phospholipase Cbeta and phospholipase D activation and inactivated by phosphorylation via diacylglycerol kinase, is responsible for the endothelin-1-induced decreases in Ca2+ transients and cell shortening
-
-
?
additional information
?
-
-
activation of a Ca2+-independent protein kinase C isozyme by 1,2-diacylglycerol, which is generated by phospholipase Cbeta and phospholipase D activation and inactivated by phosphorylation via diacylglycerol kinase, is responsible for the endothelin-1-induced decreases in Ca2+ transients and cell shortening
-
-
?
additional information
?
-
diacylglycerol kinase zeta and syntrophins play a role at multiple stages of the cell fusion process. Potential link between changes in the lipid content of the membranebilayer and reorganization of the actin cytoskeleton during myoblast fusion
-
-
?
additional information
?
-
-
diacylglycerol kinase zeta is a key determinant of cell cycle progression and differentiation of C2C12 cells
-
-
?
additional information
?
-
diacylglycerol kinase zeta is a key determinant of cell cycle progression and differentiation of C2C12 cells
-
-
?
additional information
?
-
-
diacylglycerol kinases alpha and zeta synergistically promote T cell maturation in the thymus
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Zn2+
zinc can play a non-catalytic role in DGK regulation. Pre-incubation of DGK-theta with 0.1 mM zinc ions inhibits the enzyme at pH 6.0-7.5
Mg2+
required, activates. Phosphatidylserine concentrates Mg2+ ions at the interface
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
no inhibition by ATP, ADP, sodium pyrophosphate, and beta-glycerophosphate
-
R59022
-
specifc inhibitor of diacylglycerol kinase. Treatment significantly increases glucose transport, p38 and MKK3/6 activation in myotubes. The R59022-induced glucose transport is blocked by SB203580, a specific p38 inhibitor. R59022 fails to stimulate both possible known mechanisms to enhance glucose transport, an IRS1-PI3K-Akt pathway, muscle contraction signaling or GLUT1 and GLUT4 expression
R59022
is an effective inhibitor of purified DGK-theta in vitro and in vivo
R59949
is an effective inhibitor of purified DGK-theta in vitro and in vivo
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cholesterol
DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such cholesterol
phosphatidylethanolamine
DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such as phosphatidylethanolamine
phosphatidylserine
broadens the pH-dependent activity when the enzyme is assayed in cytosolic extracts. Phosphatidylserineconcentrates Mg2+ ions at the interface
additional information
isozyme DGK-teta is dependent on an activating accessory protein containing a poly-basic region, the broadening of the pH profile of DGK-theta is also dependent on a PBR-containing activator
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the broadening of the pH profile of DGK-theta is also dependent on a PBR-containing activator
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
DGKdelta is the most abundant isoform in murine brown adipose tissue
isozyme DGK-theta shows a striking predominate localization in the nervous system
-
expression of diacylglycerol kinase isoform alpha, delta, epsilon, zeta, or theta mRNA
-
DGKdelta is the most abundant isoform in murine white adipose tissue
-
nuclear DGKzeta increases during myogenic differentiation of mouse C2C12 myoblasts
nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
diacylglycerol kinase zeta and syntrophins, scaffold proteins of the dystrophin glycoprotein complex that bind directly to diacylglycerol kinase zeta, are spatially regulated during fusion of cultured cells. Both proteins accumulate with the GTPase Rac1 at sites where fine filopodia mediate the initial contact between myoblasts. Diacylglycerol kinase zeta codistributes with the Ca2+-dependent cell adhesion molecule N-cadherin at nascent cell contacts
-
DGKdelta and DGKzeta are the most abundant isoforms in murine muscle tissue
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
DGK-zeta export from nucleus to cytoplasm is regulated by a leucine-rich nuclear export signal through the exportin chromosome regional maintenance protein 1
in the basal state, DGKzeta resides in the cytoplasm, but upon appropriate cellular events, it translocates to different parts of the cell in order to perform its biological role
DGKalpha is a cytosolic enzyme that must relocate to the membrane in response to receptor stimulation to exercise its function
-
sterile alpha-motif of diacylglycerol kinase delta1 forms helical polymers through a head-to-tail interaction. Disruption of polymerization by mutations constitutively localizes the enzyme to the plasma membrane
DGKalpha is a cytosolic enzyme that must relocate to the membrane in response to receptor stimulation to exercise its function
involvement of isoform diacylglycerol kinase zeta in cell-cycle progression
isoform diacylglycerol kinase zeta localizes to the nucleus during interphase including G1, S, and G2 phases in NIH-3T3 cells and in proliferating spermatogonia in the testis. Enzyme is associated with chromatin and dissociates from chromatin during mitotic phase
a portion of intracellular DGKzeta protein is localized to the nucleus
DGK-zeta displays a functional independent nuclear export signal sequence between the amino acid residues 362-370
-
activation and relocalization to plasma membrane of DGKalpha is a direct consequence of PI3K activation
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
DGKepsilon prevents cardiac hypertrophy and progression to heart failure under chronic pressure overload
malfunction
metabolism
isoform DGKdelta interacts with melanoma antigen gene-D1 adaptor protein and Praja-1 E3 ubiquitin-protein ligase, and enhances the ubiquitination of serotonin transporter through Praja-1. Isoform DGKdelta interacts with serotonin transporter and induces serotonin transporter degradation in an activity-dependent manner through the Praja-1 ubiquitin ligase-proteasome system
physiological function
malfunction
knockdown of DGKfzeta in cultured neurons decreases spine density
malfunction
-
transformed mouse embryo fibroblasts from mice that have a genetic deletion of DGKdelta exhibit decreased levels of many phospholipids and neutral lipids compared with wild-type mouse embryonic fibroblasts. DGKdelta knockout leads to down-regulation of enzymes responsible for fatty acid synthesis and lowers the amount of many lipid species within the cell
malfunction
isoform DGKdelta knockout mice exhibit serotonin transporter inhibitor-sensitive obsessive-compulsive disorder-like behaviors. Moreover, serotonin transporter protein levels are markedly increased in the DGKdelta-deficient brain
malfunction
the suppression of DGKdelta expression increases the phosphorylation levels of conventional and novel protein kinase C (cnPKCs). Furthermore, DGKdelta suppression increases the levels of cyclin D1 and phospho-cnPKCs even at the first 24 h of myogenic differentiation
physiological function
DGKalpha has a central role in modulating T cell anergy through its ability to control DAG levels, which likely activates RasGRP1 and possibly other proteins
physiological function
DGKs broadly regulate signaling events by virtue of their ability to provide 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) for the synthesis of phosphatidylinositols, isoform DGKzeta activates phosphatidylinositol-4-phosphate 5-kinase type Ialpha, DGKzeta modulates Rac1 activation to influence neurite outgrowth, DGKzeta modulates mTor activation and immune cell signaling
physiological function
DGKzeta has an important biological function in the nucleus where it appears to modulate the cell cycle by metabolizing 1,2-diacylglycerol
physiological function
diacylglycerol kinase zeta regulates actin cytoskeleton reorganization through dissociation of Rac1 from RhoGDI
physiological function
isoform DGKf appears to form a multi-protein complex with functionally related proteins to organize efficient 1,2-diacylglycerol and 1,2-diacyl-sn-glycerol 3-phosphate signaling pathways at excitatory synapses, the DGKzeta isoform at excitatory postsynaptic sites is critically involved in spine maintenance, DGKzeta promotes neurite outgrowth
physiological function
membrane localization of DGKalpha acts as a switch-off signal for Ras activation, mediated by localization to the membrane of Ras-GRP1, DGKalpha is a negative regulator of the T cell activation program, DGKalpha activity is required for optimal chemotactic response of neutrophils, whereas it halts their oxidative burst, DGKalpha is a negative modulator of diacylglycerol signaling, DGKalpha activity modulates the mTOR pathway to prevent cell cycle transition, DGKalpha is an indicator of cell quiescence, DGKalpha is a positive regulator of cell proliferation and migration
physiological function
nuclear DGK-zeta downregulates the expression of cyclin D1 and increased the expression of TIS21/BTG2/PC3
physiological function
-
DGKdelta promotes de novo lipid synthesis is through signal transduction pathways, overview
physiological function
the enzyme plays important roles is the nervous system
physiological function
isoform DGKalpha is involved in the vitamin E-induced amelioration of diabetic nephropathy in vivo
physiological function
isoform DGKalpha plays a crucial role in the amelioration of diabetic nephropathy and contributes to the effect of epigallocatechin gallate on diabetic nephropathy
physiological function
isoform DGKdelta regulates the early differentiation of C2C12 myoblasts via controlling the down-regulation of cyclin D1 expression
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DGKE_MOUSE
564
1
63635
Swiss-Prot
Secretory Pathway (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
104000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
diacylglycerol kinase zeta is associated with chromatin and dissociates from chromatin during mitotic phase
additional information
-
sterile alpha-motif of diacylglycerol kinase delta1 forms helical polymers through a head-to-tail interaction. Disruption of polymerization by mutations constitutively localizes the enzyme to the plasma membrane
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
T57P
-
mutant with reduced activity, used for construcution of fusion protein for genetic selection of soluble mutants
additional information
additional information
construction of mutant protein lacking the regulatory N-terminus and both C1 domains. Mutant is enzymatically active. deletion analysis reveals that the C1 domains are essential for plasma membrane targeting in intact cells but unnecessary for catalytic activity. The C-terminal sequence is required for membrane-binding in a phosphatidic acid-dependent manner. In the absence of the calcium binding domain, receptor-dependent translocation of the truncated protein is regulated by phosphorylation of residue Y335
additional information
-
creation of thoracic transverse aortic constriction in transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta and wild-type mice. Increases in heart weight at 4 weeks after thoracic transverse aortic constriction are attenuated in diacylglycerol kinase zeta transgenic mice compared with wild-type mice. Increases in interventricular septal thickness, dilatation of the left ventricular cavity, and decreases in left ventricular systolic function in wild-type mice are observed at 4 weeks after surgery and are attenuated in diacylglycerol kinase zetatransgenic mice. Contrary to wild-type, cardiac fibrosis and gene induction of type I and type III collagens, but not transforming growth factor are blocked in diacylglycerol kinase zeta transgenic mice
additional information
-
deficiency for diacylglycerol kinase zeta results in impaired interleukin 12 and tumor necrosis factor alpha production following toll-like receptor stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection. Deficiency results in increased activation of the phosphatidylinositol 3-kinase-Akt pathway. Inhibition of phosphatidylinositol 3-kinase activity or treatment with phosphatidic acid can restore lipopolysaccharide-induced interleukin 12 production by diacylglycerol kinase zeta-deficient mice
additional information
deficiency for diacylglycerol kinase zeta results in impaired interleukin 12 and tumor necrosis factor alpha production following toll-like receptor stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection. Deficiency results in increased activation of the phosphatidylinositol 3-kinase-Akt pathway. Inhibition of phosphatidylinositol 3-kinase activity or treatment with phosphatidic acid can restore lipopolysaccharide-induced interleukin 12 production by diacylglycerol kinase zeta-deficient mice
additional information
-
diacylglycerol kinase delta knock-down mice reveal abnormal epiletic discharges and electrographic seizures in three out of six homozygotes
additional information
-
expression of isolated His-tagged sterile alpha-motif domain of diacylglycerol kinase delta1, comprised of residues 1097-1164. The domain forms large aggregates with a molecular weight of 250000 Dalton or greater, while calculated monomer molecular weight is 9500 Dalton
additional information
generation of double transgenic mice with cardiac-specific overexpression of both diacylglycerol kinase zeta and G-protein subunit alphaq. Diacylglycerol kinase zeta prevents cardiac dysfunction, determined by dilatation of left ventricular dimensions, reduction of left ventricular fractional shortening, and marked increases in left ventricular end-diastolic pressure in G-protein subunit alphaq transgenic mice. Translocation of protein kinase C isoforms, phosphorylation activity of c-jun N-terminal kinase and p38 mitogen-activated protein kinase in G-protein subunit alphaq transgenic mice are attenuated by diacylglycerol kinase zeta?. Diacylglycerol kinase zeta improves the survival rate of G-protein subunit alphaq transgenic mice
additional information
-
generation of double transgenic mice with cardiac-specific overexpression of both diacylglycerol kinase zeta and G-protein subunit alphaq. Diacylglycerol kinase zeta prevents cardiac dysfunction, determined by dilatation of left ventricular dimensions, reduction of left ventricular fractional shortening, and marked increases in left ventricular end-diastolic pressure in G-protein subunit alphaq transgenic mice. Translocation of protein kinase C isoforms, phosphorylation activity of c-jun N-terminal kinase and p38 mitogen-activated protein kinase in G-protein subunit alphaq transgenic mice are attenuated by diacylglycerol kinase zeta?. Diacylglycerol kinase zeta improves the survival rate of G-protein subunit alphaq transgenic mice
additional information
-
generation of heterozygous diacylglycerol kinase delta whole-body knockout mice. Diacylglycerol kinase delta haploinsufficiency increases diacylglycerol content, reduces peripheral insulin sensitivity, insulin signaling, and glucose transport, and leads to age-dependent obesity. Metabolic flexibility is impaired
additional information
-
generation of mice lacking both diacylglycerol kinase alpha and zeat. Absence of both diacylglycerol kinases results in a severe decrease in the number of CD4+CD8- and CD4-CD8+ single-positive thymocytes correlating with increased diacylglycerol kinase-mediated signaling. Positive selection, but not negative selection, is impaired in diacylglycerol kinase alpha-/- zeta -/- mice. The developmental blockage in diacylglycerol kinase alpha-/- zeta -/- mice can be partially overcome by treatment with phosphatidic acid. Decreased diacylglycerol kinase activity also promotes thymic lymphomagenesis accompanying elevated Ras and Erk1/2 activation
additional information
in mouse ventricular myocytes overexpressing diaclyglycerol kinase zeta, the effect induced by endothelin-1 on Ca2+ transients and cell shortening are abolished
additional information
-
in mouse ventricular myocytes overexpressing diaclyglycerol kinase zeta, the effect induced by endothelin-1 on Ca2+ transients and cell shortening are abolished
additional information
-
overexpression of diacylglycerol kinase zeta blocks cells in G1 phase of cell cycle. Cell cycle arrest is accompanied by decreased levels of retinoblastoma protein phosphorylated on Ser-807/811. Down-regulation by siRNA increases the number of cells in both the S and G2/M phases of the cell cycle and prevents the cell cycle block characterizing C2C12 cell myogenic differentiation
additional information
overexpression of diacylglycerol kinase zeta blocks cells in G1 phase of cell cycle. Cell cycle arrest is accompanied by decreased levels of retinoblastoma protein phosphorylated on Ser-807/811. Down-regulation by siRNA increases the number of cells in both the S and G2/M phases of the cell cycle and prevents the cell cycle block characterizing C2C12 cell myogenic differentiation
additional information
transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta. Left ventricular chamber dilatation, reduction of left ventricular systolic function and increases in left ventricular weight and lung weight at 4 weeks after myocardial infarction are attenuated in transgenic mice compared with wild-type mice. In the noninfarct area, fibrosis fraction and upregulation of profibrotic genes, such as transforming growth factor-1, collagen type I, and collagen type III, are blocked in transgenic mice. Survival rate at 4 weeks after myocardial infarction is higher in transgenic mice than in wild-type
additional information
-
transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta. Left ventricular chamber dilatation, reduction of left ventricular systolic function and increases in left ventricular weight and lung weight at 4 weeks after myocardial infarction are attenuated in transgenic mice compared with wild-type mice. In the noninfarct area, fibrosis fraction and upregulation of profibrotic genes, such as transforming growth factor-1, collagen type I, and collagen type III, are blocked in transgenic mice. Survival rate at 4 weeks after myocardial infarction is higher in transgenic mice than in wild-type
additional information
nuclear export signal mutant forms of DGK-zeta accumulate in the nucleus to a much greater extent than wild type DGK-zeta
additional information
-
nuclear export signal mutant forms of DGK-zeta accumulate in the nucleus to a much greater extent than wild type DGK-zeta
additional information
-
generation of enzyme-deficient DGKdelta-KO mouse embryonic fibroblasts
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
activation of tyrosine kinases is required for membrane stabilization of DGKalpha, phosphorylation of DGKalpha at Tyr335 appears to be essential for membrane localization
the enzyme exhibits a mean half-life of approximately 5.1 h in cultured cells
the enzyme is stabilized during prolonged incubations in the presence of phospholipid vesicles, in a diacylglycerol-independent manner
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant FLAG-tagged splicing variants delta1 and delta2 from 3T3-L1 pre-adipocytes by affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene dgkdelta, both splicing variants delta1 and delta2 are recombinantly expressed as FLAG-tagged proteins in enzyme-deficient 3T3-L1 pre-adipocytes, real-time RT-PCR enzyme expression analysis during adipocyte differentiation shows that 3T3-L1 preadipocytes transfected with DGKdelta have no evidence of differentiation to adipocytes
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
DGKdelta expression is down-regulated in the early stage of C2C12 myogenic differentiation
DGKzeta mRNA levels are increased in mice on a high-fat diet, but are lower in those that become obese by a high-fat diet
p53-mediated upregulation of DGKalpha mRNA in mouse-derived cells, (PPAR)-gamma-dependent DGKalpha upregulation in endothelial cells, DMSO-based differentiation of promyelocytic HL-60 cells into a neutrophilic phenotype correlates with increase in the expression of DGKalpha, DGKalpha expression is upregulated in cancer
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
DGKepsilon is a therapeutic target to prevent cardiac hypertrophy and progression to heart failure
analysis
-
generation of a soluble mutant selection assay based on a library of random diacylglycerol kinase delta1 mutants of sterile alpha-motif and murine dihydrofolate reductase as the selectable marker
medicine
medicine
comparison of transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta and wild-type mice in streptozotocin-induced diabetic and non-diabetic conditions. After 8 weeks, decreases in heart weight and heart weight/body weight ratio in diabetic wild-type mice are inhibited in transgenic mice. Decreases in left ventricular end-diastolic diameter and fractional shortening observed in wild-type mice are attenuated in transgenic mice. Thinning of the interventricular septum and the posterior wall in diabetic wild-type hearts are blocked in transgenic mice. Reduction of transverse diameter of cardiomyocytes isolated from the left ventricle in diabetic wild-type mice is attenuated in transgenic mice. Cardiac fibrosis was much less in diabetic transgenic than in diabetic wild-type mice
medicine
-
creation of thoracic transverse aortic constriction in transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta and wild-type mice. Increases in heart weight at 4 weeks after thoracic transverse aortic constriction are attenuated in diacylglycerol kinase zeta transgenic mice compared with wild-type mice. Increases in interventricular septal thickness, dilatation of the left ventricular cavity, and decreases in left ventricular systolic function in wild-type mice are observed at 4 weeks after surgery and are attenuated in diacylglycerol kinase zetatransgenic mice. Contrary to wild-type, cardiac fibrosis and gene induction of type I and type III collagens, but not transforming growth factor are blocked in diacylglycerol kinase zeta transgenic mice
medicine
deficiency for diacylglycerol kinase zeta results in impaired interleukin 12 and tumor necrosis factor alpha production following toll-like receptor stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection
medicine
-
diacylglycerol kinase delta haploinsufficiency increases diacylglycerol content, reduces peripheral insulin sensitivity, insulin signaling, and glucose transport, and leads to age-dependent obesity. Metabolic flexibility is impaired
medicine
-
diacylglycerol kinase delta knock-down mice reveal abnormal epiletic discharges and electrographic seizures in three out of six homozygotes
medicine
diacylglycerol kinase zeta blocks cardiac dysfunction and progression to lethal heart failure by activated G-protein subunit alphaq protein without detectable adverse effects in the in-vivo heart
medicine
transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta. Left ventricular chamber dilatation, reduction of left ventricular systolic function and increases in left ventricular weight and lung weight at 4 weeks after myocardial infarction are attenuated in transgenic mice compared with wild-type mice. In the noninfarct area, fibrosis fraction and upregulation of profibrotic genes, such as transforming growth factor-1, collagen type I, and collagen type III, are blocked in transgenic mice. Survival rate at 4 weeks after myocardial infarction is higher in transgenic mice than in wild-type
medicine
isoform DGKalpha can be used as strategy for treating diabetic nephropathy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Outram, S.V.; Crompton, T.; Merida, I.; Varas, A.; Martinez, A.C.
Diacylglycerol kinase alpha activity promotes survival of CD4+ 8+ double positive cells during thymocyte development
Immunology
105
391-398
2002
Mus musculus
Cipres, A.; Carrasco, S.; Merino, E.; Diaz, E.; Krishna, U.M.; Falck, J.R.; Martinez-A, C.; Merida, I.
Regulation of Diacylglycerol Kinase a by Phosphoinositide 3-Kinase Lipid Products
J. Biol. Chem.
278
35629-35635
2003
Mus musculus
Evangelisti, C.; Tazzari, P.L.; Riccio, M.; Fiume, R.; Hozumi, Y.; fala, F.; Goto, K.; Manzoli, L.; Cocco, L.; Martelli, A.M.
Nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
FASEB J.
21
3297-3307
2007
Mus musculus, Mus musculus (Q80UP3)
Evangelisti, C.; Bortul, R.; Fala, F.; Tabellini, G.; Goto, K.; Martelli, A.M.
Nuclear diacylglycerol kinases: emerging downstream regulators in cell signalling networks
Histol. Histopathol.
22
573-579
2007
Chlorocebus aethiops, Cricetulus griseus, Homo sapiens, Mus musculus, Rattus norvegicus
Liu, C.H.; Machado, F.S.; Guo, R.; Nichols, K.E.; Burks, A.W.; Aliberti, J.C.; Zhong, X.P.
Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii
J. Exp. Med.
204
781-792
2007
Mus musculus, Mus musculus (Q80UP3)
Zha, Y.; Marks, R.; Ho, A.W.; Peterson, A.C.; Janardhan, S.; Brown, I.; Praveen, K.; Stang, S.; Stone, J.C.; Gajewski, T.F.
T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha
Nat. Immunol.
7
1166-1173
2006
Mus musculus
Crotty, T.; Cai, J.; Sakane, F.; Taketomi, A.; Prescott, S.M.; Topham, M.K.
Diacylglycerol kinase delta regulates protein kinase C and epidermal growth factor receptor signaling
Proc. Natl. Acad. Sci. USA
103
15485-15490
2006
Mus musculus
Leach, N.T.; Sun, Y.; Michaud, S.; Zheng, Y.; Ligon, K.L.; Ligon, A.H.; Sander, T.; Korf, B.R.; Lu, W.; Harris, D.J.; Gusella, J.F.; Maas, R.L.; Quade, B.J.; Cole, A.J.; Kelz, M.B.; Morton, C.C.
Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice
Am. J. Hum. Genet.
80
792-799
2007
Mus musculus, Homo sapiens (Q16760), Homo sapiens
Niizeki, T.; Takeishi, Y.; Arimoto, T.; Takahashi, H.; Shishido, T.; Koyama, Y.; Goto, K.; Walsh, R.A.; Kubota, I.
Cardiac-specific overexpression of diacylglycerol kinase zeta attenuates left ventricular remodeling and improves survival after myocardial infarction
Am. J. Physiol.
292
H1105-H1112
2007
Mus musculus (Q80UP3), Mus musculus
Takahashi, N.; Nagamine, M.; Tanno, S.; Motomura, W.; Kohgo, Y.; Okumura, T.
A diacylglycerol kinase inhibitor, R59022, stimulates glucose transport through a MKK3/6-p38 signaling pathway in skeletal muscle cells
Biochem. Biophys. Res. Commun.
360
244-250
2007
Mus musculus
Bilim, O.; Takeishi, Y.; Kitahara, T.; Arimoto, T.; Niizeki, T.; Sasaki, T.; Goto, K.; Kubota, I.
Diacylglycerol kinase zeta inhibits myocardial atrophy and restores cardiac dysfunction in streptozotocin-induced diabetes mellitus
Cardiovasc. Diabetol.
7
2
2008
Mus musculus (Q80UP3), Mus musculus
Chibalin, A.V.; Leng, Y.; Vieira, E.; Krook, A.; Bjoernholm, M.; Long, Y.C.; Kotova, O.; Zhong, Z.; Sakane, F.; Steiler, T.; Nylen, C.; Wang, J.; Laakso, M.; Topham, M.K.; Gilbert, M.; Wallberg-Henriksson, H.; Zierath, J.R.
Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance
Cell
132
375-386
2008
Mus musculus, Rattus norvegicus, Homo sapiens (Q16760), Homo sapiens
Abramovici, H.; Gee, S.H.
Morphological changes and spatial regulation of diacylglycerol kinase-zeta, syntrophins, and Rac1 during myoblast fusion
Cell Motil. Cytoskeleton
64
549-567
2007
Mus musculus (Q80UP3)
Harada, M.; Takeishi, Y.; Arimoto, T.; Niizeki, T.; Kitahara, T.; Goto, K.; Walsh, R.A.; Kubota, I.
Diacylglycerol kinase zeta attenuates pressure overload-induced cardiac hypertrophy
Circ. J.
71
276-282
2007
Mus musculus
Niizeki, T.; Takeishi, Y.; Kitahara, T.; Arimoto, T.; Koyama, Y.; Goto, K.; Mende, U.; Kubota, I.
Diacylglycerol kinase zeta rescues G alpha q-induced heart failure in transgenic mice
Circ. J.
72
309-317
2008
Mus musculus (Q80UP3), Mus musculus
Merino, E.; Sanjuan, M.A.; Moraga, I.; Cipres, A.; Merida, I.
Role of the diacylglycerol kinase alpha-conserved domains in membrane targeting in intact T cells
J. Biol. Chem.
282
35396-35404
2007
Mus musculus (O88673)
Hasegawa, H.; Nakano, T.; Hozumi, Y.; Takagi, M.; Ogino, T.; Okada, M.; Iseki, K.; Kondo, H.; Watanabe, M.; Martelli, A.M.; Goto, K.
Diacylglycerol kinase zeta is associated with chromatin, but dissociates from condensed chromatin during mitotic phase in NIH3T3 cells
J. Cell. Biochem.
105
756-765
2008
Mus musculus (Q80UP3)
Nishimaru, K.; Arimoto, T.; Takeishi, Y.; Kubota, I.; Ishii, K.; Endoh, M.
Overexpression of diacylglycerol kinase zeta inhibits endothelin-1-induced decreases in Ca2+ transients and cell shortening in mouse ventricular myocytes
J. Mol. Cell. Cardiol.
44
520-526
2008
Mus musculus (Q80UP3), Mus musculus
Guo, R.; Wan, C.K.; Carpenter, J.H.; Mousallem, T.; Boustany, R.M.; Kuan, C.T.; Burks, A.W.; Zhong, X.P.
Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta
Proc. Natl. Acad. Sci. USA
105
11909-11914
2008
Mus musculus
Harada, B.T.; Knight, M.J.; Imai, S.; Qiao, F.; Ramachander, R.; Sawaya, M.R.; Gingery, M.; Sakane, F.; Bowie, J.U.
Regulation of enzyme localization by polymerization: polymer formation by the SAM domain of diacylglycerol kinase delta 1
Structure
16
380-387
2008
Mus musculus
Merida, I.; Avila-Flores, A.; Garcia, J.; Merino, E.; Almena, M.; Torres-Ayuso, P.
Diacylglycerol kinase alpha, from negative modulation of T cell activation to control of cancer progression
Adv. Enzyme Regul.
49
174-188
2009
Mus musculus (O88673), Homo sapiens (P23743)
Niizeki, T.; Takeishi, Y.; Kitahara, T.; Arimoto, T.; Ishino, M.; Bilim, O.; Suzuki, S.; Sasaki, T.; Nakajima, O.; Walsh, R.A.; Goto, K.; Kubota, I.
Diacylglycerol kinase-epsilon restores cardiac dysfunction under chronic pressure overload: a new specific regulator of Galpha(q) signaling cascade
Am. J. Physiol. Heart Circ. Physiol.
295
H245-H255
2008
Mus musculus (Q9R1C6), Mus musculus
Topham, M.K.; Epand, R.M.
Mammalian diacylglycerol kinases: molecular interactions and biological functions of selected isoforms
Biochim. Biophys. Acta
1790
416-424
2009
Mus musculus (O88673), Mus musculus (Q80UP3), Mus musculus (Q9R1C6)
Cai, J.; Abramovici, H.; Gee, S.H.; Topham, M.K.
Diacylglycerol kinases as sources of phosphatidic acid
Biochim. Biophys. Acta
1791
942-948
2009
Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Sus scrofa, Mus musculus (Q80UP3)
Evangelisti, C.; Gaboardi, G.C.; Billi, A.M.; Ognibene, A.; Goto, K.; Tazzari, P.L.; McCubrey, J.A.; Martelli, A.M.
Identification of a functional nuclear export sequence in diacylglycerol kinase-zeta
Cell Cycle
9
384-388
2010
Mus musculus (Q80UP3), Mus musculus
Evangelisti, C.; Astolfi, A.; Gaboardi, G.C.; Tazzari, P.; Pession, A.; Goto, K.; Martelli, A.M.
TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest
Cell. Signal.
21
801-809
2009
Mus musculus (Q80UP3), Mus musculus
Kim, K.; Yang, J.; Kim, E.
Diacylglycerol kinases in the regulation of dendritic spines
J. Neurochem.
112
577-587
2010
Rattus norvegicus (O08560), Mus musculus (Q80UP3)
Abramovici, H.; Mojtabaie, P.; Parks, R.J.; Zhong, X.P.; Koretzky, G.A.; Topham, M.K.; Gee, S.H.
Diacylglycerol kinase zeta regulates actin cytoskeleton reorganization through dissociation of Rac1 from RhoGDI
Mol. Biol. Cell
20
2049-2059
2009
Mus musculus (Q80UP3)
Tu-Sekine, B.; Goldschmidt, H.; Petro, E.; Raben, D.
Diacylglycerol kinase ?: regulation and stability.
Adv. Biol. Regul.
53
118-126
2013
Mus musculus (Q6P5E8)
Shulga, Y.V.; Loukov, D.; Ivanova, P.T.; Milne, S.B.; Myers, D.S.; Hatch, G.M.; Umeh, G.; Jalan, D.; Fullerton, M.D.; Steinberg, G.R.; Topham, M.K.; Brown, H.A.; Epand, R.M.
Diacylglycerol kinase delta promotes lipogenesis
Biochemistry
52
7766-7776
2013
Mus musculus
Mizuno, S.; Kado, S.; Goto, K.; Takahashi, D.; Sakane, F.
Diacylglycerol kinase zeta generates dipalmitoyl-phosphatidic acid species during neuroblastoma cell differentiation
Biochem. Biophys. Rep.
8
352-359
2016
Mus musculus (Q80UP3)
Lu, Q.; Murakami, C.; Hoshino, F.; Murakami, Y.; Sakane, F.
Diacylglycerol kinase delta destabilizes serotonin transporter protein through the ubiquitin-proteasome system
Biochim. Biophys. Acta
1865
158608
2020
Mus musculus (E9PUQ8)
Sakai, H.; Murakami, C.; Matsumoto, K.I.; Urano, T.; Sakane, F.
Diacylglycerol kinase delts controls down-regulation of cyclin D1 for C2C12 myogenic differentiation
Biochimie
151
45-53
2018
Mus musculus (E9PUQ8)
Hayashi, D.; Wang, L.; Ueda, S.; Yamanoue, M.; Ashida, H.; Shirai, Y.
The mechanisms of ameliorating effect of a green tea polyphenol on diabetic nephropathy based on diacylglycerol kinase alpha
Sci. Rep.
10
11790
2020
Mus musculus (O88673)
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