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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cyclic beta-1,2-glucans of Rhizobium may function during legume nodulation. These molecules may become highly substituted with phosphoglycerol moieties from the head group of phosphatidylglycerol; diglyceride is a by-product of this reaction (K. J. Miller, R. S. Gore, and A. J. Benesi, J. Bacteriol. 170:4569-4575, 1988). We recently reported that R. meliloti 1021 produces a diacylglycerol kinase (EC 2.7.1.107) activity that shares several properties with the diacylglycerol kinase enzyme of Escherichia coli (W. P. Hunt, R. S. Gore, K. J. Miller, Appl. Environ. Microbiol. 57:3645-3647, 1991). A primary function of this rhizobial enzyme is to recycle diglyceride generated during cyclic beta-1,2-glucan biosynthesis. In the present study, we report the cloning and initial characterization of a single-copy gene from R. meliloti 1021 that encodes a diacylglycerol kinase homolog; this homolog can complement a diacylglycerol kinase deficient strain of E. coli. The sequence of the rhizobial diacylglycerol kinase gene was predicted to encode a protein of 137 amino acids; this protein shares 32% identity with the E. coli enzyme. Analysis of hydropathy and the potential to form specific secondary structures indicated a common overall structure for the two enzymes. Because diglyceride metabolism and cyclic beta-1,2-glucan biosynthesis are metabolically linked, future studies with diacylglycerol kinase mutants of R. meliloti 1021 should further elucidate the roles of the cyclic beta-1,2-glucans in the Rhizobium-legume symbiosis.
Mol Plant Microbe Interact
PMID:Identification of the diacylglycerol kinase structural gene of Rhizobium meliloti 1021. 133 1

A 3.1 kbp cDNA clone encoding diacylglycerol (DG) kinase of 80 kDa (80K-DG kinase) was isolated from a rat brain cDNA library. The deduced amino acid sequence was 82% homologous to previously identified porcine 80K-DG kinase and contained zinc finger-like sequences, E-F hand motifs and ATP-binding sites similar to the porcine counterpart. By in situ hybridization histochemistry of rat brain at postnatal week 3, the expression signals for 80K-DG kinase mRNA appeared predominantly on somata of discrete cells in the white matter, and the expression pattern was similar to that of the myelin-specific proteins. In immunohistochemistry using the antibody against bacterially expressed DG kinase-fusion protein, numerous fibrous or dot-like structures exhibiting the immunoreactivity were concentrated in the white matter and they were arranged to radiate in the cerebral cortex and the cerebellar granular layer in a pattern almost identical to that of oligodendrocytes. No neuronal cells exhibited the immunoreactivity. The present finding thus strongly suggests that 80K-DG kinase is expressed specifically in the oligodendrocytes, but not neurons, and may be involved in the myelin formation and metabolism. In addition, the intense hybridization signals and the immunoreactivity for this protein were detected in the entire medulla of the thymus and the periarterial lymphatic area of the splenic white pulp both of which represent T-cell-dependent areas.
Brain Res Mol Brain Res 1992 Nov
PMID:Gene cloning, sequence, expression and in situ localization of 80 kDa diacylglycerol kinase specific to oligodendrocyte of rat brain. 133 2

In the first report in this series we described the relationships and evolution of 152 individual proteins of the EF-hand subfamilies. Here we add 66 additional proteins and define eight (CDC, TPNV, CLNB, LPS, DGK, 1F8, VIS, TCBP) new subfamilies and seven (CAL, SQUD, CDPK, EFH5, TPP, LAV, CRGP) new unique proteins, which we assume represent new subfamilies. The main focus of this study is the classification of individual EF-hand domains. Five subfamilies--calmodulin, troponin C, essential light chain, regulatory light chain, CDC31/caltractin--and three uniques--call, squidulin, and calcium-dependent protein kinase--are congruent in that all evolved from a common four-domain precursor. In contrast calpain and sarcoplasmic calcium-binding protein (SARC) each evolved from its own one-domain precursor. The remaining 19 subfamilies and uniques appear to have evolved by translocation and splicing of genes encoding the EF-hand domains that were precursors to the congruent eight and to calpain and to SARC. The rates of evolution of the EF-hand domains are slower following formation of the subfamilies and establishment of their functions. Subfamilies are not readily classified by patterns of calcium coordination, interdomain linker stability, and glycine and proline distribution. There are many homoplasies indicating that similar variants of the EF-hand evolved by independent pathways.
J Mol Evol 1992 May
PMID:Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories. 160 95

The monokine interleukin-1 alpha (IL-1) induces a glucose-dependent increase in insulin secretion, an effect tentatively attributed to its ability to increase beta cell phosphoinositide (PI) hydrolysis. In the present experiments, the effects of the protein kinase C inhibitor staurosporine (20 nM), the calcium channel antagonist nitrendipine (5 microM), and the diacylglycerol kinase inhibitor monooleoylglycerol (MOG, 25 microM) on 40 nM IL-1-induced increments in insulin release from perifused islets and inositol phosphate levels in [3H]inositol prelabeled islets were assessed. In perifused islets, insulin secretion in response to IL-1 in the presence of 7 mM glucose averaged 313 +/- 43 pg/islet/min 35-40 min after the onset of stimulation. Release from control islets perifused in the presence of 7 mM glucose alone averaged 56 +/- 6 pg/islet/min at this time point. The addition of staurosporine together with IL-1 reduced insulin secretion at this time point to 88 +/- 21 pg/islet/min. This level of IL-1 caused significant increases in inositol phosphate accumulation in the presence of 7 mM glucose but not 2.75 mM glucose. Staurosporine was without a significant effect on inositol phosphate accumulation in response to the monokine. In contrast, nitrendipine (5 microM) inhibited insulin release and inositol phosphate accumulation in a parallel fashion. Finally, MOG significantly amplified release to the monokine without significantly affecting its impact on inositol phosphate accumulation. Nitrendipine or staurosporine blocked this amplifying effect of MOG on secretion. These results emphasize the role of PI hydrolysis in IL-1-induced insulin secretion and suggest further that calcium influx is essential for IL-1 to fully activate both PI hydrolysis and insulin secretion.
Mol Cell Endocrinol 1991 Dec
PMID:Influence of staurosporine, nitrendipine and monooleoylglycerol on interleukin-1-induced insulin secretion and phosphoinositide hydrolysis. 166 56

The diacylglycerol kinase inhibitor monooleoylglycerol (MOG) produced a dose-dependent increase in both phosphoinositide (PI) hydrolysis and insulin secretion in the presence of a substimulatory glucose level (2.75 mM). This effect could not be reproduced by the combination of oleic acid plus glycerol, potential metabolic products derived from MOG catabolism. At a level (25 microM) which has no significant effect on beta cell insulin secretion or PI hydrolysis in the presence of 2.75 mM glucose, MOG significantly potentiated the insulin stimulatory effect of the sulfonylurea tolbutamide (200 microM) in the presence of 7 mM glucose. This heightened insulin secretory response and PI hydrolysis were effectively attenuated by the calcium channel blocker nitrendipine (0.5 microM). These findings indicate that MOG has complex effects on beta cell performance. It promises, however, to be a useful probe in assessing how events associated with increases in PI hydrolysis influence insulin secretion.
Mol Cell Endocrinol 1990 Jan 22
PMID:Influence of monooleoylglycerol on islet cell phosphoinositide hydrolysis and insulin secretion. 215 36

Endothelin (ET-1) receptors were studied in the C-6 glia cell line. ET-1 binds to C-6 cells in a temperature- and time-dependent manner, with an apparent Kd of 1.16 +/- 0.07 10(-10) M and a Bmax of 96,500 +/- 6000 sites/cell (mean +/- SEM, n = 27). Stimulation of protein kinase C (PKC) with the diacylglycerol (DAG) analog phorbol 12-myristate 13-acetate (PMA) resulted in a decrease in the number of receptors in a dose-dependent manner. Inhibition of PKC with H-7 eliminated the effect of PMA on the reduction of binding sites. Treatment with exogenous 1-oleoyl-2-acetyl-sn-glycerol (OAG) and 1,2-dioctanoyl-sn-glycerol (DOG), release of endogenous DAG with phospholipase C, and inhibition of the metabolism of DAG with the diacylglycerol kinase inhibitor R 59022 also resulted in a decrease in the number of receptors. The effect of these agents was inhibited by H-7. ET-1-mediated down-regulation of receptors was also demonstrated, but the down-regulation was not affected by H-7 or by depletion of cellular PKC with chronic, high dose of PMA. Internalization constants of ET-1-receptor complex was also measured according to the model of Wiley and Cunningham (Cell 25 (1981) 433). PMA- and ET-1-mediated down-regulation of receptors was associated with an increase in the endocytosis constant for the hormone-receptor complex and a decrease in the rate of insertion of receptor into the plasma membrane. PMA, but not ET-1, increased the rate of endocytosis of unoccupied receptors. Radioiodinated ET-1 was crosslinked to the receptor after binding, extracted and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A band at 66 kDa was obtained. These studies show that ET-1 and PKC activation produce down-regulation of ET-1 membrane receptors and that ET-1-mediated down-regulation probably does not involve the activation of PKC.
Mol Cell Endocrinol 1990 Apr 17
PMID:ET-1 receptors in C-6 cells: homologous down-regulation and modulation by protein kinase C. 216 63

U-57 908 (RHC 80267) inhibited diacylglycerol (DG) lipase activity in soluble and microsomal subcellular fractions from cardiac myocytes isolated from adult rat hearts; half-maximal inhibition was observed at a concentration of 3.5 microM. Monoacylglycerol lipase activity was much less sensitive to inhibition, but U-57 908 reduced lipoprotein lipase activity in cardiac myocytes with the same sensitivity as observed for DG lipase. DG kinase activity was not inhibited by U-57 908. DG metabolism by intact cardiac myocytes was studied in incubations with a cell-permeable DG analog, [3H]-dioctanoylglycerol (diC8). DiC8 was mainly metabolized by conversion to mono-octanoylglycerol (monoC8) and glycerol (lipase pathway); much less radioactivity was incorporated into the triacylglycerol and total phospholipid fractions. U-57 908 reduced the loss of radioactivity from the exogenous diC8 substrate, with a corresponding decline in the formation of radiolabelled monoC8 and glycerol. The incorporation of radioactivity into phospholipids was slightly reduced, but triacylglycerol synthesis from diC8 was increased in the presence of U-57 908. Therefore, U-57 908 is an effective inhibitor of DG metabolism by the lipase pathway in intact cardiac myocytes.
J Mol Cell Cardiol 1990 Sep
PMID:Inhibition of diacylglycerol metabolism in isolated cardiac myocytes by U-57 908 (RHC 80267), a diacylglycerol lipase inhibitor. 217 92

We have shown earlier that the 12-lipoxygenase product of arachidonic acid (AA), 12-hydroxyeicosatetraenoic acid (12-HETE), plays an important role in mediating angiotensin II (AII)-induced aldosterone secretion (J. Clin. Invest. (1987) 80, 1763). In the present study, we have evaluated whether diacylglycerol (DG) is the source of arachidonic acid giving rise to this 12-HETE. Treatment of rat adrenal glomerulosa cells with a DG lipase inhibitor, RHC 80267, which prevents conversion of DG to AA and HETEs, blocked AII-induced aldosterone and 12-HETE formation. In contrast, a DG kinase inhibitor, R59022, which prevents conversion of DG to phosphatidic acid, potentiated AII-induced aldosterone and 12-HETE formation. These two inhibitors block DG metabolism which would be expected to lead to increased DG levels and protein kinase C activity and AII-induced steroidogenesis. However, only R59022 potentiated AII action while RHC 80267 was inhibitory. This suggests that conversion of DG to AA and 12-HETE is important for AII action. Further proof for this was obtained by measuring [3H]AA-labeled DG levels. The combination of the inhibitors significantly potentiated AII-induced DG formation even though this same combination was inhibitory on AII-induced aldosterone and 12-HETE. Thus, the inhibitory effect of RHC 80267 is due to blockade of AA release and not of DG formation. These results suggest that DG plays a dual role in AII action, both as an activator of protein kinase C and as a source of AA for 12-HETE formation.
Mol Cell Endocrinol 1990 Aug 20
PMID:Key role of diacylglycerol-mediated 12-lipoxygenase product formation in angiotensin II-induced aldosterone synthesis. 217 2

The effect of a reduction in protein kinase C activity on the metabolism of exogenous [3H]diC8 by freshly isolated smooth muscle cells from rabbit aorta and cultured A10 smooth muscle cells was determined. The metabolism of [3H]diC8 by both smooth muscle cell preparations was predominantly by hydrolysis to yield monoC8 and glycerol (lipase pathway); very little radioactivity was incorporated into phospholipids. Diacylglycerol lipase activity measured in vitro with A10 cell homogenates was much greater than diacylglycerol kinase activity. The addition of the protein kinase C inhibitor H-7 to incubations of isolated aortic smooth muscle cells and cultured A10 cells had no significant effect on the metabolism of [3H]diC8. Protein kinase C activity in cultured A10 cells preincubated for 20 h with a phorbol ester was reduced to 14% of control as a consequence of down-regulation, but diC8 metabolism was not changed. Therefore, protein kinase C does not regulate the metabolism of diacylglycerols in aortic smooth muscle cells.
Mol Cell Biochem 1990 Jul 17
PMID:Protein kinase C does not regulate diacylglycerol metabolism in aortic smooth muscle cells. 223 6

Diacylglycerol (DG) metabolism by intact cardiac myocytes isolated from adult rat hearts and by broken cell preparations from myocytes was investigated in experiments with [3H]dioctanoylglycerol (diC8), a cell-permeable diacylglycerol analog. In a low-speed supernatant fraction, the Km and Vmax for DG kinase activity (formation of phosphatidic acid) was 22 microM and 110 nmol/h/mg, respectively, whereas the Km and Vmax for DG lipase activity (formation of monoacylglycerol) was 80 microM and 1000 nmol/h/mg. At a substrate concentration of 80 microM diC8, lipase activity was 7-fold greater than kinase activity. The majority of DG kinase activity was recovered in the soluble subcellular fraction; DG lipase activity was localized in a microsomal fraction. When [3H]diC8 was incubated with intact cardiac myocytes, 10-fold more radioactivity was incorporated into the products of the lipase pathway (monoacylglycerol and free glycerol) as compared to incorporation into the total phospholipid fraction which contained phosphatidic acid. This predominance of metabolism by hydrolysis through the lipase pathway was observed consistently when the incubation time, content of cardiac myocytes and concentration of exogenous diC8 was varied. Therefore, results from both in vitro determinations of enzyme activities in broken cell preparations and flux studies with intact cells have indicated that the lipase pathway is the principal enzymatic mechanism for the metabolism of diC8 in cardiac myocytes.
J Mol Cell Cardiol 1989 Aug
PMID:Metabolism of dioctanoylglycerol by isolated cardiac myocytes. 255 Jun 55


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