Metabolism of Farnesol: Phosphorylation of Farnesol by Rat Liver Microsomal and Peroxisomal Fractions

Westfall, Denise; Aboushadi, Nahla; Shackelford, Janis E.; Krisans, Skaidrite K.

doi:10.1006/bbrc.1996.6014

Cited by 54 publications

(49 citation statements)

References 21 publications

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“…However, kinase(s) using CTP as a specific substrate has already been reported for other eukaryotic systems in two cases. Farnesol, when incubated with microsomal fractions of Nicotiana tabacum cell cultures or rat liver, is specifically labeled with CTP (33,35). However, this activity is very different from the one documented in this report regarding the location of the phosphorylated products, since phosphorylated farnesol has been found to be located in mitochondrial and peroxisomal fractions.…”

Section: Discussioncontrasting

confidence: 90%

“…Labeling of X and Y in the Presence of CTP␥S-As far as we know, although some phosphotransferase activities can utilize CTP as the phosphate donor (35,36), plant lipid phosphorylation activities using CTP as the preferential substrate have not yet been reported in the literature. In order to have a further confirmation that CTP is indeed the substrate, we have enzymatically synthesized CTP␥S from ATP␥S, CDP, and NDPK in vitro (for details, see "Experimental Procedures").…”

Section: Lipid Phosphorylation In Chloroplast Envelopementioning

confidence: 99%

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Lipid Phosphorylation in Chloroplast Envelopes

Müller¹,

Meylan-Bettex²,

Eckstein³

et al. 2000

Journal of Biological Chemistry

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Lipid phosphorylation takes place within the chloroplast envelope. In addition to phosphatidic acid, phosphatidylinositol phosphate, and their corresponding lyso-derivatives, we found that two novel lipids underwent phosphorylation in envelopes, particularly in the presence of carrier-free [ The lipid kinase activity involved in this reaction was specifically inhibited in the presence of cytosine 5-O-(thiotriphosphate) (CTP␥S) and sensitive to CTP chase, thereby showing that both lipids are phosphorylated by an envelope CTP-dependent lipid kinase. The lipids were identified as phosphorylated galactolipids by using an acid hydrolysis procedure that generated galactose 6-phosphate. CTP␥S did not affect the import of the small ribulose-bisphosphate carboxylase/oxygenase subunit into chloroplasts, the possible physiological role of this novel CTP-dependent galactolipid kinase activity in the chloroplast envelope is discussed.One of the main functions assigned to the chloroplast is its ability to assimilate CO 2 under illumination. This key activity must be separated from the rest of the cell by a selective membrane barrier, namely the envelope, which is one of the three main plastid compartments in addition to thylakoids and the stroma. The envelope is constituted of two membranes, the inner and the outer envelopes, each having its own specific characteristic and property (1).Lipid phosphorylation occurs in chloroplast envelope membranes (2). The first identified lipids incorporating phosphate from [␥-32 P]ATP in isolated envelope vesicles were lysophosphatidic acid (LPA), 1 phosphatidic acid (PA), phosphatidylinositol phosphate (PIP), and lysophosphatidylinositol phosphate (LPIP). At the present time, the functions of these phospholipids are not known in chloroplasts, but: (i) they might produce substrates for lipid biosynthesis pathways; for instance, PIP can serve as substrate for a phosphatidylinositol-4,5-phosphate kinase and eventually can be hydrolyzed in second messengers like inositol 1,4,5-trisphosphate and DAG (3); (ii) they could directly interact with intracellular proteins to affect their location and/or activity; (iii) they might also change the local topology of other lipids, thereby modifying electrostatic interactions of membrane components. Indeed, in mammalian systems, LPA and PA, as minor cell lipids, are likely to act as potent activators of plasma membrane tyrosine kinase via G protein activation and intracellular protein kinases (4, 5). PA is the product of sn-diacylglycerol phosphorylation catalyzed by a diacylglycerol kinase (6). In plant signaling pathways, PA is also derived from PC via phospholipase D (7) and from diacylglycerol pyrophosphate (8). The production of LPA usually occurs after a first rapid accumulation of DAG, followed by phosphorylation, and activation of a PA-specific phospholipase A 2 within the plasma membrane (9). In plants, a diacylglycerol kinase from Arabidopsis thaliana (10) and LPA, a product of inducible PLA 2 (11), have been identified, but their specific role a...

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Section: Discussioncontrasting

confidence: 90%

Section: Lipid Phosphorylation In Chloroplast Envelopementioning

confidence: 99%

Lipid Phosphorylation in Chloroplast Envelopes

Müller¹,

Meylan-Bettex²,

Eckstein³

et al. 2000

Journal of Biological Chemistry

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“…Thus, over the time course of a typical neuronal action potential, L-type channels were the most effectively inhibited channel isoform, followed by N-type channels (IC 50 values obtained from dose-response curves for peak current inhibition (32,33). In hepatic tissue, farnesol is catabolized into farnesoic acid and dicarboxylic acids (34) or is re-phosphorylated into farnesyl pyrophosphate by a specific kinase (35,36). Multistep branches of the pathway are marked with dotted arrows for simplicity.…”

Section: Farnesol Mediates a Low Affinity Block Of All Types Of Highmentioning

confidence: 99%

Modulation of Neuronal Voltage-gated Calcium Channels by Farnesol

Roullet¹,

Spaetgens²,

Burlingame³

et al. 1999

Journal of Biological Chemistry

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The modulation of presynaptic voltage-dependent calcium channels by classical second messenger molecules such as protein kinase C and G protein ␤␥ subunits is well established and considered a key factor for the regulation of neurotransmitter release. However, little is known of other endogenous mechanisms that control the activity of these channels. Here, we demonstrate a unique modulation of N-type calcium channels by farnesol, a dephosphorylated intermediate of the mammalian mevalonate pathway. At micromolar concentrations, farnesol acts as a relatively non-discriminatory rapid open channel blocker of all types of high voltage-activated calcium channels, with a mild specificity for Ltype channels. However, at 250 nM, farnesol induces an N-type channel-specific hyperpolarizing shift in channel availability that results in ϳ50% inhibition at a typical neuronal resting potential. Additional experiments demonstrated the presence of farnesol in the brain (rodents and humans) at physiologically relevant concentrations (100 -800 pmol/g (wet weight)). Altogether, our results indicate that farnesol is a selective, high affinity inhibitor of N-type Ca 2؉ channels and raise the possibility that endogenous farnesol and the mevalonate pathway are implicated in neurotransmitter release through regulation of presynaptic voltage-gated Ca 2؉ channels.Calcium entry into the cytosol is a crucial mediator of a range of cellular responses, including cell proliferation and neurotransmitter release (1, 2). Internal calcium levels are precisely regulated through differential expression and modulation of multiple types of voltage-dependent calcium channels (3-6). These channels are key pharmacological targets, and the identification of novel means of regulating calcium channel activity remains of critical importance for the treatment of a variety of neurological disorders, including migraines, pain, and ischemia (7, 8).Molecular cloning has identified genes encoding at least nine different neuronal calcium channel ␣ 1 subunits (termed ␣ 1A through ␣ 1I ). Functional expression studies have shown that ␣ 1A encodes P-and Q-type calcium channels (9, 10); ␣ 1B defines an -conotoxin GVIA-sensitive N-type channel (11, 12); ␣ 1C , ␣ 1D , and ␣ 1F are L-type calcium channels (13-16); ␣ 1G ␣ 1H , and ␣ 1I are members of the family of T-type calcium channels (17-19); and ␣ 1E is a unique calcium channel with properties common to both high and low threshold calcium channels (20,21). The activities of voltage-dependent calcium channels are extensively modulated by cytoplasmic messenger molecules. Although the short-term modulation of these channels by protein kinases (22,23,24) and G protein ␤␥ subunits (25-31) has been well documented, little is known about mechanisms that mediate their long-term regulation.Farnesol is an isoprenoid intermediate of the mevalonate pathway, produced by dephosphorylation of farnesyl pyrophosphate ( Fig. 1) (32, 33). This pathway plays a central role in cell growth and differentiation; controls the production of ub...

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“…Asterisks indicate significant differences from the Col-0 control (*P < 0.05, **P < 0.01 and ***P < 0.001) as determined by Student's t test. (Inoue et al, 1994;Crick et al, 1995Crick et al, , 1997Fliesler and Keller, 1995;Westfall et al, 1997;Bentinger et al, 1998;Thai et al, 1999). Here, we show that Arabidopsis membranes possess farnesol kinase activity and that ATP, CTP, GTP and UTP are phosphoryl donor substrates of farnesol kinase (Figure 1).…”

Section: Aba Regulation Of Folk Gene Expressionmentioning

confidence: 53%

“…However, the physiological role of farnesyl diphosphatase is not clear. Indeed, farnesol is toxic to plant cells at high concentrations, and numerous studies have demonstrated the phosphorylation of farnesol to farnesyl phosphate (FP) and subsequent phosphorylation of FP to FPP (Inoue et al, 1994;Crick et al, 1995Crick et al, , 1997Fliesler and Keller, 1995;Westfall et al, 1997;Bentinger et al, 1998;Thai et al, 1999;Hemmerlin and Bach, 2000;Hemmerlin et al, 2006). For example, when tobacco microsomal membranes were used as a source of kinase activity, phosphorylation of farnesol to FP occurred in the presence of CTP, GTP or UTP as a phosphoryl donor, but phosphorylation of FP to FPP occurred only in the presence of CTP as a phosphoryl donor (Thai et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Farnesol kinase is involved in farnesol metabolism, ABA signaling and flower development in Arabidopsis

2011

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SUMMARYFarnesol, which is toxic to plant cells at high concentrations, is sequentially phosphorylated to farnesyl phosphate and farnesyl diphosphate. However, the genes responsible for the sequential phosphorylation of farnesol have not been identified and the physiological role of farnesol phosphorylation has not been fully elucidated. To address these questions, we confirmed the presence of farnesol kinase activity in Arabidopsis (Arabidopsis thaliana) membranes and identified the corresponding gene (At5g58560, FOLK). Heterologous expression in recombinant yeast cells established farnesol as the preferred substrate of the FOLK-encoded kinase. Moreover, loss-of-function mutations in the FOLK gene abolished farnesol kinase activity, caused an abscisic acid-hypersensitive phenotype and promoted the development of supernumerary carpels under water-stress conditions. In wild-type plants, exogenous abscisic acid repressed FOLK gene expression. These observations demonstrate a role for farnesol kinase in negative regulation of abscisic acid signaling, and provide molecular evidence for a link between farnesol metabolism, abiotic stress signaling and flower development.

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Metabolism of Farnesol: Phosphorylation of Farnesol by Rat Liver Microsomal and Peroxisomal Fractions

Cited by 54 publications

References 21 publications

Lipid Phosphorylation in Chloroplast Envelopes

Lipid Phosphorylation in Chloroplast Envelopes

Modulation of Neuronal Voltage-gated Calcium Channels by Farnesol

Farnesol kinase is involved in farnesol metabolism, ABA signaling and flower development in Arabidopsis

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