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Cellular Signalling 16 (2004) 983 – 989
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Review article
Diacylglycerol kinases
Bai Luo, Debra S. Regier, Stephen M. Prescott, Matthew K. Topham *
The Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112-5550, USA
Received 12 March 2004; accepted 29 March 2004
Available online 6 May 2004
Abstract
Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol to form phosphatidic acid. In most cases, members of this large family of
enzymes appear to bind and regulate proteins activated by either diacylglycerol or phosphatidic acid. Proteins that appear to be regulated, in part,
by DGKs include protein kinase Cs, RasGRPs, and phosphatidylinositol kinases. By modulating the activity of these proteins, DGKs potentially
affect a number of biological events including—but likely not limited to—cell growth, neuronal transmission, and cytoskeleton remodeling.
D 2004 Elsevier Inc. All rights reserved.
Keywords: Diacylglycerol kinases; Diacylglycerol; Phosphatidic acid; Lipid signalling; Phosphatidylinositol; Nucleus; Cytoskeleton
1. Introduction
Numerous intracellular signalling pathways are initiated
when phospholipase C (PLC) enzymes hydrolyze phosphatidylinositol-4,5-bisphosphate (PIP2) [1]. The products of
this reaction, diacylglycerol (DAG) and inositol-1,4,5-triphosphate, transiently rise and then fall back to basal levels.
These second messengers initiate two predictable events:
inositol-1,4,5-triphosphate binds to intracellular receptors
causing calcium release from intracellular stores, while
diacylglycerol recruits and often activates signalling proteins that contain cysteine-rich, C1 domains. Several proteins contain C1 domains, the best known are protein kinase
C (PKC) isoforms, which regulate a broad array of cell
functions [2]. Until recently, most of the physiological
effects of DAG were attributed to activation of the PKCs.
However, other DAG targets exist that likely also contribute
to the downstream effects of diacylglycerol [3]. For example, DAG binds and activates the family of four RasGRP
nucleotide exchange factors [4 – 7], it recruits the chimaer-
Abbreviations: DGK, diacylglycerol kinase; DAG, diacylglycerol; PLC,
phospholipase C; PIP2, phosphatidylinositol-4,5-bisphosphate; PKC, protein kinase C; PA, phosphatidic acid; PH, pleckstrin homology; SAM,
sterile alpha motif; RA, Ras association; PIP5K, phosphatidylinositol 4phosphate 5-kinase; PI, phosphatidylinositol; NLS, nuclear localization
signal.
* Corresponding author. Tel.: +1-801-585-0304; fax: +1-801-5856345.
E-mail address: [email protected] (M.K. Topham).
0898-6568/$ - see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.cellsig.2004.03.016
ins—Rac GTPase-activating proteins—to membrane compartments [8], and it can activate some ion channels [9].
Because DAG can modulate so many signalling proteins—
and consequently affects numerous signalling events—it is
crucial that intracellular DAG levels be tightly regulated.
The adverse effects of excessive and/or prolonged DAG
signalling are best illustrated by the tumor-promoting effects
of the phorbol esters. These compounds are DAG analogues
that can bind C1 domains, but are very slowly metabolized.
Their tumorigenic effects are likely due to persistent activation of proteins that bind phorbol esters such as PKC and
RasGRP isoforms. The effects of the phorbol esters have led
many to hypothesize that prolonged elevation of DAG—
which is seen in tumors and in transformed cell lines
[10,11]—is the equivalent of an endogenous phorbol ester.
DAG can be metabolized in three ways: hydrolysis of a
fatty acyl chain by diacylglycerol lipase to generate a
monoacylglycerol and a free fatty acid, addition of CDPcholine or -ethanolamine to form phosphatidylcholine or
phosphatidylethanolamine, or by phosphorylating the free
hydroxyl group to produce phosphatidic acid (PA). Under
most circumstances, its conversion to PA is considered the
major route for metabolism of signalling DAG, and the
reaction is catalyzed by the diacylglycerol kinases.
2. The diacylglycerol kinase gene family
DGK isoforms have been identified in organisms such as
Caenorhabditis elegans [12,13], Drosophila melanogaster
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B. Luo et al. / Cellular Signalling 16 (2004) 983–989
[14 –16], and Arabidopsis thaliana [17,18], while no DGK
gene has been identified in yeast. Bacteria express only one
DGK enzyme, and it is an integral membrane protein
capable of phosphorylating in vitro other lipids such as
ceramide [19]. Bacterial DGK does not appear to have
structural elements allowing regulation of its activity, suggesting that it is constitutively active and is limited by
access to its substrate(s).
Based on shared structural motifs, DGK isoforms in
multicellular organisms are classified into five subtypes.
Because most of these organisms express at least one DGK
ortholog of each subtype, the five DGK subtypes appear to
have distinct functions. Nine mammalian DGK isoforms
have been identified (Fig. 1). The heterogeneity of this gene
family is similar to the PKC and PLC families, suggesting
that the DGKs are not simply lipid biosynthetic enzymes,
but also have signalling roles, since enzymes involved in
biosynthetic pathways usually do not have extended families. All DGK isoforms have a catalytic domain that is
necessary for kinase activity. Each catalytic domain has an
ATP-binding site similar to protein kinase catalytic domains
with the sequence Gly-X-Gly-X-X-Gly. Mutation of the
second glycine in this motif to an aspartate or alanine
renders the DGK catalytically inactive [20 – 22]. Mutation
of that glycine to an aspartate was first noted in the
Drosophila DGK, dDGK2 [15]. The mutant dDGK2 protein
is expressed in the Drosophila strain rdgA, and causes rapid
retinal degeneration after birth. Although protein kinase and
DAG kinase catalytic domains share some similarities, there
are important structural differences between them that may
allow DGK catalytic domains to access DAG in lipid
bilayers, a property not required for most protein kinases.
In most cases, the DGK catalytic domains are composed of
a single motif, but DGKs y and D have bipartite catalytic
domains [23,24], indicating that these and perhaps other
DGK catalytic domains may function as two independent
units in a coordinated fashion. The DGK catalytic domains
may also require other motifs for maximal activity because
several DGK catalytic domains have very little DAG kinase
activity when expressed as isolated subunits (M.K.T., unpublished observations). However, Sakane et al. [25] demonstrated that when expressed as an isolated subunit, the
catalytic domain of DGKa retained about 60% of the
activity of the wild-type enzyme. However, to compare
their DAG kinase activities, this group used 100,000 g
supernatants, which may have eliminated most of the more
active, membrane-bound, wild-type enzyme in the 100,000
g pellets. Moreover, DGKa has an inhibitory motif that,
Fig. 1. The mammalian DGK family. Based on structural motifs, the nine mammalian DGKs are divided into five subtypes. All mammalian DGKs have C1 and
catalytic (kinase) domains. Also shown are EF hand motifs, pleckstrin homology (PH) domains, MARCKS homology domains, nuclear localization signals
(NLS), sterile alpha motifs (SAM), PDZ-binding domains, ankyrin repeats, and Ras association (RA) domains. Alternative splicing of DGKs y, ~, and D
generates even more structural diversity. Several DGKh splice variants have also been identified, but are not shown, and many mammalian DGKs contain other
unique structural domains of unclear significance that are also not shown.
B. Luo et al. / Cellular Signalling 16 (2004) 983–989
when deleted, yields a fully active enzyme (see below).
Sakane et al. [25] found that the isolated DGKa catalytic
domain had only 1/3 the activity of this fully active mutant.
Thus, it appears that mammalian DGK catalytic domains,
unlike bacterial DGK, require other motifs such as C1
domains for maximal activity. This suggests that these other
motifs function in coordination with the catalytic domain.
All DGKs have at least two cysteine-rich regions homologous to the C1A and C1B motifs of PKCs [26]. In theory,
these domains may bind DAG, perhaps localizing DGKs to
where DAG accumulates. However, no DGK C1 domain
has so far been conclusively shown to bind DAG. In fact,
structural predictions suggest that most DGK C1 domains
may not bind DAG. For example, Hurley et al. [26] noted
that the amino acid sequences of most DGK C1 domains
differed enough from those in PKCs that many DGK C1
domains may not bind DAG. Most DGKs tested were
unable to bind long-lived DAG-like analogues such as
PDBu [27]. However, the inability of DGK C1 domains
to bind DAG-like molecules may simply reflect exquisite
selectivity of DGK C1 domains for authentic DAG, unlike
other C1 domains such as those in PKCs which appear to be
more promiscuous. Houssa and van Blitterswijk [28] noted
that in DGKs, the C1 domain closest to the catalytic domain
is highly conserved, including an extended motif of 15
amino acids not present in C1 domains of other proteins or
in the DGK C1 motifs further from the catalytic domain.
They noted that conserved residues in this extended motif
may be critical for DAG kinase activity. Taken together,
these data suggest that DGK C1 domains are structurally
different from C1 domains in other proteins and that the
different C1 domains of a single DGK isoform may have
unique functions. However, distinct functions of individual
C1 domains remain to be definitively demonstrated.
In addition to the C1 and catalytic domains, DGKs have
other regulatory domains that form the basis for dividing
them into five subtypes. Type I DGKs [29 – 31] have
calcium-binding EF hand motifs and are more active in
the presence of calcium [32]. Type II DGKs have pleckstrin
homology (PH) domains at their amino termini [23,24]. This
domain in DGKy has been shown to bind weakly and
nonselectively to phosphatidylinositols [33]. Type II DGKs
also have sterile alpha motifs (SAM domain) at their
carboxy termini. Nagaya et al. [21] demonstrated that the
SAM domain of DGKy helped localize it to the endoplasmic
reticulum, and this domain also appeared necessary for
homo- and hetero-oligomerization of DGKs y and D
[34,35]. The physiological significance of oligomerization
is not clear at this point, although in some cases, it may
suppress DAG kinase activity [34]. DGKq, the only type III
enzyme, has an unusual specificity toward acyl chains of
DAG, strongly preferring a specific fatty acid—arachidonate—at the sn-2 position [36]. Its preference for arachidonate-DAG suggests that DGKq may be a component of the
biochemical pathway that accounts for the enrichment of
phosphatidylinositols with arachidonate [37]. Type IV
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DGKs [38,39] have domains similar to the phosphorylation
site domain of the MARCKS protein. This domain in both
DGKs ~ and L functions as a nuclear localization signal and
it is phosphorylated by conventional PKC isoforms[22,39].
Its phosphorylation in DGK~ not only reduces nuclear
localization [22], but also suppresses DAG kinase activity
[40] and causes it to dissociate from the PKC [41]. Type IV
DGKs also have four ankyrin repeats and carboxy terminal
PDZ-binding domains [42]. The type V enzyme, DGKu, has
three C1 domains, a putative PH domain, and a Ras
association (RA) domain [43]. The function of its RA
domain is not clear, and although most RA domains bind
RasGTP, van Blitterswijk found that DGKu did not bind
Ras [44].
3. Phosphatidic acid produced by DGKs may have
signalling properties
Several reports indicate that phosphatidic acid, the product of the DGK reaction, has signalling properties. For
example, studies have indicated that PA can stimulate
DNA synthesis and is potentially mitogenic [45,46]. However, these properties may have also been caused by
contaminating lysophosphatidic acid. Other work indicates
that PA is involved in vesicle trafficking [47] and can bind
and regulate the activity of numerous enzymes, including
the phosphatidylinositol 5-kinases [48], Ras-GAP [49],
PKC~ [50], PAK1 [51], and protein phosphatase 1 [52].
Phosphatidic acid also helps recruit Raf to the Ras signalling
complex [53]. While the majority of signalling PA is likely
derived from the phospholipase D reaction [54], it is
possible that PA produced by DGKs also has a signalling
role. This suggests that in some cases after terminating a
DAG signal, DGKs subsequently activate a PA signalling
event. Flores et al. [55] presented evidence in T lymphocytes suggesting that PA from the DGK reaction had a
potential role in progression of cells to S phase of the cell
cycle. We recently demonstrated that DGK~ associated with
type Ia phosphatidylinositol 4-phosphate 5-kinase (PIP5K),
a protein activated by PA [56]. We found that co-expression
of DGK~ with the PIP5K increased its phosphatidylinositol
kinase activity. In addition to these examples, it is possible
that DGKs modulate the activity of other phosphatidic acid
protein targets.
4. Regulation of DGK activity
Activation of the DGKs is complex and unique for each
DGK isotype. In most cases, DGKs must translocate to a
membrane compartment to access DAG. However, translocation does not necessarily activate the enzyme [57]. In
addition, DGK activity can be modified by other cofactors
such as lipids and calcium, and several DAG kinases are
also regulated by post-translational modifications. Finally,
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tissue-specific alternative splicing of DGKs h, g, y, ~, and
D, and probably other isotypes, allows for additional regulation [31,34,35,58,59]. This complexity permits cell- or
tissue-specific regulation of each DGK isotype depending
on the availability of cofactors and the type of stimulus that
the cell receives.
DGKa is perhaps the best example of the contextually
dependent, differential regulation of DGKs. DGKa translocated to at least two different membrane compartments in
T lymphocytes depending upon the agonist used to activate
the cells: from the cytosol to a perinuclear region in T cells
stimulated with IL-2 [55,60], and to the plasma membrane
upon activation of the T cell antigen receptor [20]. Once at a
membrane compartment, the DAG kinase activity of DGKa
can be modified by the availability of several cofactors.
Calcium is known to bind to EF hand structures and
stimulated DGKa activity in vitro [32]. Sanjuan et al. [20]
demonstrated that deleting the EF hand motifs of DGKa
caused it to associate with the plasma membrane and
significantly increased its DAG kinase activity. This observation led to the hypothesis that in the absence of calcium,
the EF hand structures of DGKa inhibit DAG kinase
activity—possibly by masking a motif necessary for catalytic activity—and somehow reduce membrane association.
Binding calcium releases the inhibition and causes translocation to the membrane, allowing maximal DAG kinase
activity. When associated with the membrane, the activity of
DGKa is further modified by binding to lipid components:
phosphatidylserine, sphingosine [61,62], and the phosphatidylinositol (PI) 3-kinase lipid products, PI-3,4-P2 and PI3,4,5-P3 [63], activated DGKa in vitro and likely in vivo as
well. Finally, DGKa can be phosphorylated by several
protein kinases including some PKC isoforms [64,65] and
Src kinase [66], which may further enhance its DAG kinase
activity. Thus, numerous events are required to fully activate
DGKa, combinations of which can fine-tune its activity to
the appropriate level.
Similar to DGKa, other DGK isotypes appear to be
sensitively regulated by a number of factors. For example,
type II DGKs have a PH domain that may affect intracellular
localization by interacting with either phosphatidylinositols
or with other proteins. Indeed, the PH domain of the type II
DGKy could bind inositol phosphates [33]. However, the
binding was nonselective and weaker than a typical high
affinity protein – lipid interaction, suggesting that it may not
be a physiological interaction. Its DAG kinase activity was
not affected by PIP2 [23]. In contrast, the activity of DGK
types III and IV can be modified by phosphatidylinositols
and phosphatidylserine in opposing ways. DGKq, the type
III enzyme, was inhibited by both PIP2 and phosphatidylserine, whereas DGK~ was activated by both lipids [67].
Like DGKa, the subcellular localization of type IV DGKs is
exquisitely regulated. These enzymes have a nuclear localization signal that can be regulated by PKC phosphorylation
[22,39]. Additionally, members of the syntrophin family of
scaffolding proteins further regulate the subcellular location
of DGK~ by associating with its carboxy terminal PDZbinding domain, anchoring the protein in the cytoplasm
[42]. Further, Davidson et al. [68] recently demonstrated
that activating the type I gonadotropin-releasing hormone
receptor caused DGK~ to associate with active Src kinase
and translocate to the plasma membrane. Association with
Src significantly enhanced its DAG kinase activity. Finally,
DGKu, a type V DGK, can be regulated through its
association with active RhoA: binding this GTPase abolished its DAG kinase activity [44]. Thus, depending on the
context of activation, the availability of cofactors, and the
activation state of protein kinases, DGKs can be differentially regulated.
5. DAG kinase activity is confined to specific cell
compartments
A number of reports demonstrating agonist-dependent
translocation of DGKs to distinct membrane compartments
suggest that DGK activity is restricted to localized DAG
pools generated after activation of receptors. Perhaps the
best evidence of spatially restricted DAG kinase activity
was demonstrated by van der Bend et al. [69]. This group
measured DAG kinase activity in cells following receptor
activation—which caused physiological DAG production—
or after treating the cells with exogenous PLC—which
caused global, nonspecific DAG generation. They detected
significant DAG kinase activity upon activating a receptor,
but found very little DAG kinase activity after treating the
cells with exogenous PLC. Their data suggested that DGKs
are active only in spatially restricted compartments following physiological generation of DAG. Consistent with this
conclusion, Nurrish et al. [12] found in C. elegans that dgk1, an ortholog of human DGKu, regulated DAG signalling
that was necessary for acetylcholine release. Their data
suggested a model where serotonin signalling—which
inhibits locomotion—activated the DGK to reduce DAG
accumulation.
DGKs appear to be active in a number of cell compartments. For example, Nagaya et al. [21] demonstrated that
overexpressed DGKy partly localized in the endoplasmic
reticulum, while Abramovici et al. [70] found endogenous
DGK~ at the neuromuscular junction. Several groups have
noted DGK activity in the cell fractions containing cytoskeleton components. For example, Tolias et al. [71] noted
that DGK activity associated with a complex of proteins
including a PIP5K, Rac, Rho, Cdc42, and Rho-GDI, all of
which regulate cytoskeleton dynamics. We found that
several DGK isotypes co-immunoprecipitated with either
Rac, Rho, or Cdc42 when overexpressed in cells (M.K.T.
and B.L., unpublished observations), and Houssa et al. [44]
showed that active RhoA associated with DGKu. Additionally, we found that DGK~ interacted with human PIP5K
type Ia and increased its activity by generating phosphatidic acid [56]. The physiological significance of these
B. Luo et al. / Cellular Signalling 16 (2004) 983–989
interactions is not entirely clear, but there are data demonstrating that DGKs can modulate cytoskeleton remodeling.
For example, DGK inhibitors—which primarily affect type
I enzymes—augmented platelet secretion and aggregation
[72], and Abramovici et al. [70] recently demonstrated that
expression of a DGK~ mutant that localized strongly with
the plasma membrane enhanced membrane ruffles and
caused the formation of large intracellular vesicles. Consistent with an effect on cytoskeleton dynamics, endogenous
DGK~ co-purified with components of the cytoskeleton
[70] and it localized at the leading edge of both glioblastoma cells [73] and C2 myoblasts [70]. Together, these
data suggest that DGKs have a broad role in regulating the
cytoskeleton, but at this point, their specific roles are not
clear.
The nucleus has a phosphatidylinositol cycle that is
regulated separately from the plasma membrane PI signalling [74]. Like its extranuclear counterpart, nuclear DAG
signalling appears to be compartmentalized. Indeed, D’Santos et al. [75] demonstrated independently fluctuating pools
of nuclear DAG which had distinct fatty acid compositions.
This complexity is not surprising because diverse stimuli
can lead to generation of nuclear DAG. For example,
different growth factors (e.g. IGF-1 or thrombin) stimulated
temporally distinct pulses of nuclear DAG [76,77], and
several groups have demonstrated that nuclear DAG fluctuates independently of extranuclear DAG during the cell
cycle [74]. Nuclear DAG was shown to peak shortly before
S phase, suggesting that it may participate in the G1/S
transition [78]. Most data support the conclusion that
nuclear DAG promotes cell growth. Consistent with this,
and emphasizing the importance of nuclear DAG signalling
in the cell cycle, we found that cells overexpressing
DGK~—which partly localized in the nucleus—accumulated at the G0/G1 transition, presumably because the kinase
reduced nuclear DAG [22]. Several other DGKs have been
detected in the nucleus. DGKs a and L, translocated to the
nucleus [39,55,60], while a significant fraction of DGKu
localized there constitutively [57]. By transfecting different
DGK isotypes into COS-7 cells, we detected DGKs h, g, y,
and q in the nucleus (M.K.T., unpublished observations).
Nuclear DGKs appear to be confined to separate, distinct
regions of the nucleus: DGKs u, ~, and L were noted in
discrete regions within the body of the nucleus [22,39,
57,79] while DGKa appeared to predominantly localize
around its periphery [55]. Combined with the complexity
of nuclear DAG signalling, these data suggest that within
the nucleus, DGKs regulate distinct pools of signalling
DAG. Supporting this conclusion, experimental evidence
suggests contrasting roles for the nuclear DGKs a and ~:
overexpression of DGK~ inhibited progression from G1 to S
phase of the cell cycle [22], while PA generated by nuclear
DGKa appeared to be necessary for IL-2-mediated progression to S phase of the cell cycle [55]. The opposing function
of these DGKs indicates both the importance and complexity of nuclear DGK activity and lipid signalling.
987
6. DGKs bind and regulate other signalling proteins
Based on the evidence noted above, DGKs achieve
specificity of function through a combination of post-translational modifications, the availability of cofactors, and
through the availability and access to substrate DAG. DGKs
appear to achieve an additional level of specificity by
binding to protein partners in order to regulate their activity.
This concept is consistent with an emerging body of
evidence indicating that specificity in signal transduction
is often achieved by gathering appropriate protein partners
through scaffolding proteins [80]. DGKs appear to associate
with proteins that are regulated by either DAG or PA. DGK~
provides the best example of this type of regulation. It binds
and regulates at least three proteins, each of which is
significantly affected by either DAG or PA. For example,
by binding to RasGRP1, a DAG-dependent Ras guanine
nucleotide exchange factor, DGK~ regulated the active state
of Ras [73]. This regulation was selective: five other DGK
isotypes did not significantly inhibit RasGRP1. Its inhibition
of Ras was consistent with the phenotype of DGK~ knockout mice, which had hyperresponsive T cells, in part, due to
prolonged Ras activation [81]. Regulation of RasGRP
proteins may be a common theme: we found that DGK~
associated with and regulated RasGRP3 (M.K.T and D.S.R.,
unpublished observations). DGK~ also associated with
PKCa to regulate its activity [41]. Their association was
dynamic: once phosphorylated by the PKC, DGK~ no
longer associated with it. Demonstrating the specificity of
their interaction, we found that DGK~ did not bind or
regulate PKCy. In each case, the DGK modulated the
activity of its protein partner by metabolizing DAG. Conversely, we found that DGK~ also associated with and
regulated, by generating PA, human PIP5K type Ia [56].
Based on the diversity of the mammalian DGK family many
more examples of regulation through specific interactions
will likely emerge in the near future.
7. DGKee modulates signalling events through its
specificity
DAG kinases may also be responsible for enriching
phosphatidylinositols with specific lipid components. Phosphatidylinositols are enriched at the sn 2 position with
unsaturated fatty acids, usually arachidonate [37]. While it
may seem that the specific fatty acid components would
not significantly affect the signalling ability of DAG, data
suggest that some DAG targets, including PKCs, are
specifically activated by unsaturated DAG [82]. How the
fatty acid components of DAG affect target proteins is
unclear, but one could speculate that these fatty acids may
help enrich DAG in membrane microdomains where other
signalling components reside. In vitro, most DGKs do not
distinguish between the fatty acid components of DAG,
suggesting that in vivo, phosphatidylinositols maintain
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B. Luo et al. / Cellular Signalling 16 (2004) 983–989
their unsaturated fatty acid enrichment by coupling PIspecific phospholipase C enzymes with DAG kinases and
other enzymes involved in resynthesizing PIP2. Coupling
these enzymes, would maintain the fatty acid components
of PIP2. Indeed, we found that DGK~ co-immunoprecipitated with the phosphoinositide-specific PLCs h1 and g
(M.K.T. and B.L., unpublished observations) and with
human PIPK type Ia [56]. Tabellini et al. [79] demonstrated that DGKu associated with PLCh1 and human PIPK
type Ia. DGKq is unique among the DAG kinases because
it selectively phosphorylates DAG with an arachidonate—
an unsaturated fatty acid—in the sn 2 position [36]. This
selectivity suggests that DGKq may have a more prominent role than other DGKs in enriching inositol phospholipids with unsaturated fatty acids. To examine the
biological function of this DGK, we generated mice with
targeted deletion of DGKq. Proper inositol lipid signalling
is important for normal neuronal transmission, so in a
collaborative effort, we studied seizure threshold in the
mice. We found that DGKq null mice had significantly
shorter seizures following electroconvulsive shock and
they recovered faster than wild-type mice [83]. Examination of brain lipids demonstrated reduced levels of arachidonate in both PIP2 and DAG in the DGKq-deficient
mice. These experiments underscore the importance of
maintaining proper lipid composition of phosphatidylinositols and DAG and indicate that DGKq fulfills this role in
some neuronal tissues.
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8. Conclusions
Diacylglycerol kinases influence signalling events by
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