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Query: UNIPROT:P06889 (Mol)
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We report the molecular cloning of Drosophila genes encoding putative lipase homologs, Dm lip1, lip2 and lip3, the definition of their structure and the expression patterns during development. These Drosophila lipases are related to acid lipases, with a common GHSQG motif, within a more general consensus GXSXG, identified as the active site shared by all the members of lipase superfamily. The lip1 and lip3 genes are transcribed in different tissues and developmental stages, suggesting that they have different functions. The lip1 gene, coding for a protein similar to digestive lipases, is expressed in ovaries and early embryos and, with a different sized transcript, in all the other developmental stages. The lip3 gene, whose translation product is more similar to lysosomal acid lipases, is expressed only during the larval period. The lip2 gene seems non-functional. The Drosophila putative lipases do not show similarity with the Drosophila yolk proteins that are reported to have sequence similarity with lipoprotein lipases, but share a consistent similarity with lepidopteran proteins reported as egg specific or yolk proteins, probably corresponding to lipase homologs. The results reported here are discussed in relation to the evolution and functions of lipases within the between species.
J Mol Biol 1998 Mar 13
PMID:The Drosophila melanogaster lipase homologs: a gene family with tissue and developmental specific expression. 956 93

Salmonella typhimurium apeR mutations lead to overproduction of an outer membrane-associated N-acetyl phenylalanine beta-naphthyl ester-cleaving esterase that is encoded by the apeE gene (P. Collin-Osdoby and C. G. Miller, Mol. Gen. Genet. 243:674-680, 1994). This paper reports the cloning and nucleotide sequencing of the S. typhimurium apeE gene as well as some properties of the esterase that it encodes. The predicted product of apeE is a 69.9-kDa protein which is processed to a 67-kDa species by removal of a signal peptide. The predicted amino acid sequence of ApeE indicates that it is a member of the GDSL family of serine esterases/lipases. It is most similar to a lipase excreted by the entomopathogenic bacterium Photorhabdus luminescens. The Salmonella esterase catalyzes the hydrolysis of a variety of fatty acid naphthyl esters and of C6 to C16 fatty acid p-nitrophenyl esters but will not hydrolyze peptide bonds. A rapid diagnostic test reported to be useful in distinguishing Salmonella spp. from related organisms makes use of the ability of Salmonella to hydrolyze the chromogenic ester substrate methyl umbelliferyl caprylate. We report that the apeE gene product is the enzyme in Salmonella uniquely responsible for the hydrolysis of this substrate. Southern blot analysis indicates that Escherichia coli K-12 does not contain a close analog of apeE, and it appears that the apeE gene is contained in a region of DNA present in Salmonella but not in E. coli.
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PMID:The apeE gene of Salmonella typhimurium encodes an outer membrane esterase not present in Escherichia coli. 965 91

Pseudomonas aeruginosa is a prolific exporter of virulence factors and contains three of the four protein secretion systems that have been described in gram-negative bacteria. The P. aeruginosa type II general secretory pathway (GSP) is used to export the largest number of proteins from this organism, including lipase, phospholipase C, alkaline phosphatase, exotoxin A, elastase and LasA. Although these exoproteins contain no sequence similarity, they are specifically and efficiently transported by the secretion apparatus. Bacterial homologues of XcpQ (GspD), the only outer membrane component of this system, have been proposed to play the role of gatekeeper, by presumably interacting and recognizing the exported substrates to allow their passage through the outer membrane. While determining the phenotype of nonpolar deletions in each of the xcp genes, we have shown that a deletion of the P. aeruginosa strain K xcpQ does not completely abolish protein secretion. As the proposed function of XcpQ should be requisite for secretion, we searched for additional factors that could carry out this role. A cosmid DNA library from a PAK strain deleted for xcpP-Z was tested for its ability to increase protein secretion by screening for enhanced growth on lipid agar, a medium that selects for the secretion of lipase. In this manner, we have identified an XcpQ homologue, XqhA, that is solely responsible for the residual export observed in a deltaxcpQ strain, although it is not required for efficient secretion in wild-type P. aeruginosa. We have also demonstrated that this protein is capable of recognizing all of the exoproteins of P. aeruginosa, arguing against the proposed role of members of the secretin family as determinants of specificity.
Mol Microbiol 1998 Jun
PMID:Identification of an additional member of the secretin superfamily of proteins in Pseudomonas aeruginosa that is able to function in type II protein secretion. 968 Feb 12

A plasma membrane preparation of Manduca sexta ovarian follicles was shown to contain lipoprotein lipase activity that hydrolyzes the diacylglycerol moiety of the hemolymph lipoprotein, lipophorin. Kinetic analysis demonstrated that low density lipophorin (LDLp) is a better substrate for the identified lipase activity than high density lipophorin (HDLp). The activity has a pH optimum of 9-9.5 and is partially inhibited by NaCl concentrations higher than 0.5 M. Diisopropylfluorophosphate (DFP) inhibits the membrane bound lipoprotein lipase activity completely and irreversibly. Incubation of follicle plasma membranes with [3H]-DFP radiolabels a 100-kDa membrane protein that may represent the lipoprotein lipase. The present results suggest that lipoprotein lipase activity may play an important role in the uptake of lipids by M. sexta oocytes.
Insect Biochem Mol Biol
PMID:Uptake of lipids by developing oocytes of the hawkmoth Manduca sexta. The possible role of lipoprotein lipase. 969 40

Lysosomal acid lipase (LAL) is essential for the hydrolysis of the triglycerides and cholesteryl esters in lysosomes. Its deficiency produces two phenotypes, a severe infantile-onset variant, Wolman disease (WD), and a later onset variant, cholesteryl ester storage disease (CESD). A mouse model with a LAL null mutation was produced by targeting disruption of the mouse gene. Homozygote knockout mice (lal -/lal-) produce no LAL mRNA, protein or enzyme activity. The lal-/lal- mice are born in Mendelian ratios, are normal appearing at birth, and follow normal development into adulthood. However, massive accumulation of triglycerides and cholesteryl esters occurs in several organs. By 21 days, the liver develops a yellow-orange color and is approximately 1.5-2.0x larger than normal. The accumulated cholesteryl esters and triglycerides are approximately 30-fold greater than normal. The lal+/lal- mice have approximately 50% of normal LAL activity and do not show lipid accumulation. Male and female lal-/lal- mice are fertile and can be bred to produce progeny. This mouse model is a phenotypic model of human CESD, and a biochemical and histopathologic mimic of human WD. The lal-/lal- mice provide a model to determine the role of LAL in lipid metabolism and the pathogenesis of its deficiency states.
Hum Mol Genet 1998 Sep
PMID:Targeted disruption of the mouse lysosomal acid lipase gene: long-term survival with massive cholesteryl ester and triglyceride storage. 970 Jan 86

Severe hypertriglyceridemia was previously observed in mink. Affected animals had no detectable lipoprotein lipase activity, but normal amounts of lipoprotein lipase protein in post-heparin plasma. We have now cloned cDNA for lipoprotein lipase from normal mink and identified a single point mutation in the affected animals which most likely explains the deficiency of active lipase. The mutation is located in exon 6 and results in a Pro214Leu substitution. In heterozygote mink the levels of lipoprotein lipase activity and mass in post-heparin plasma were lower than in normal mink, but could not be used to identify carriers of the mutation. In some tissues (heart, muscle, kidney and lung), lipoprotein lipase activity was decreased to about 50%. In adipose tissue there seemed to be a mechanism to compensate for the mutation, resulting in increased mass and approximately the same activity of lipoprotein lipase as in animals not carrying the mutation. Mink had high lipoprotein lipase activity and mass in kidneys, although the levels of mRNA in kidney were many fold lower than in adipose tissue. Mink had very low levels of cholesteryl ester transfer protein activity in plasma. This may contribute to the high levels of HDL in this animal species.
Int J Mol Med 1998 Mar
PMID:A mutation in the lipoprotein lipase gene associated with hyperlipoproteinemia type I in mink: studies on lipid and lipase levels in heterozygotes. 985 58

Incubation of plasma of the locust Locusta migratoria, with laminarin induced the precipitation of two major proteins with molecular masses of about 260,000 (P260) and 85,000 Da (P85). This precipitation was not observed when other polysaccharides, such as curdlan, dextran, chitin, cellulose or mannan were used. P260 and P85 were purified to homogeneity by a single step on heparin-sepharose chromatography. Since all attempts to separate P260 from P85, other than the use of sodium dodecyl sulfate, were unsuccessful, it is likely that these two molecules form a complex non-covalently associated. Treatment of P260-P85 complex with N-glycosidase F showed that P260 did not appear to be glycosylated whereas 6% of P85 molecular mass was due to N-linked carbohydrates. On the other hand, no change in molecular masses of P260 or P85 was observed once the complex had been treated with lipase. SDS-PAGE and Western blots of plasma and serum stained with blue Coomassie for proteins or with highly specific polysera to P260 or P85, respectively, showed that P260 was only present in plasma and P85 remained in both samples. This indicates that P260 is likely to be one of the most abundant plasma proteins directly involved in the coagulation process in Locusta migratoria. The addition of plasma or P260-P85 complex to a hemocyte lysate supernatant prior to its activation by laminarin induced a lower protease as well as phenoloxidase activity compared with the control. This reduction of activities was not observed in the presence of serum or when P260-P85 complex was added to a fully activated proPO system.
Insect Biochem Mol Biol 1998 Dec
PMID:Two major proteins from locust plasma are involved in coagulation and are specifically precipitated by laminarin, a beta-1,3-glucan. 988 12

Elastase is a major virulence factor in Pseudomonas aeruginosa that is believed to cause extensive tissue damage during infection in the human host. Elastase is secreted in non-mucoid P. aeruginosa. It is known that secretion of most virulence factors such as elastase, lipase, exotoxin A, etc., in P. aeruginosa is greatly reduced in alginate-secreting mucoid cells isolated from the lungs of cystic fibrosis (CF) patients. We have previously reported that in mucoid P. aeruginosa, an intracellular protease cleaves the 16 kDa form of nucleoside diphosphate kinase (Ndk) to a truncated 12 kDa form. This smaller form is membrane associated and has been observed to form complexes with specific proteins to predominantly generate GTP, an important molecule in alginate synthesis. The main aim of this study was to purify and characterize this protease. The protease was purified by hydrophobic interaction chromatography of the crude extract of mucoid P. aeruginosa 8821, a CF isolate. Further analysis using a gelatin containing SDS-polyacrylamide gel detected the presence of a 103 kDa protease, which when boiled, migrated as a 33 kDa protein on a SDS-polyacrylamide gel. The first 10 amino acids from the N-terminus of the 33 kDa protease showed 100% identity to the mature form of elastase. An elastase-negative lasB::Cm knock-out mutant in the mucoid 8821 background was constructed, and it showed a non-mucoid phenotype. This mutant showed the presence of only the 16 kDa form of Ndk both in the cytoplasm and membrane fractions. We present evidence for the retention of active elastase in the periplasm of mucoid P. aeruginosa and its role in the generation of the 12 kDa form of Ndk. Finally, we demonstrate that elastase, when overproduced in both mucoid and non-mucoid cells, stimulates alginate synthesis. This suggests that the genetic rearrangements that trigger mucoidy in P. aeruginosa also allow retention of elastase in the periplasm in an active oligomeric form that facilitates cleavage of 16 kDa Ndk to its 12 kDa form for the generation of GTP, required for alginate synthesis.
Mol Microbiol 1998 Dec
PMID:Cellular function of elastase in Pseudomonas aeruginosa: role in the cleavage of nucleoside diphosphate kinase and in alginate synthesis. 998 71

Surprisingly small peptide motifs can confer critical biological functions. One example is the WRPW tetrapeptide present in the Hairy family of transcriptional repressors, which mediates recruitment of the Groucho (Gro) corepressor to target promoters. We recently showed that Engrailed (En) is another repressor that requires association with Gro for its function. En lacks a WRPW motif; instead, it contains another short conserved sequence, the En homology region 1 (eh1)/GEH motif, that is likely to play a role in tethering Gro to the promoter. Here, we characterize a repressor domain from the Goosecoid (Gsc) developmental regulator that includes an eh1/GEH-like motif. We demonstrate that this domain (GscR) mediates efficient repression in Drosophila blastoderm embryos and that repression by GscR requires Gro function. GscR and Gro interact in vitro, and the eh1/GEH motif is necessary and sufficient for the interaction and for in vivo repression. Because WRPW- and eh1/GEH-like motifs are present in different proteins and in many organisms, the results suggest that interactions between short peptides and Gro represent a widespread mechanism of repression. Finally, we investigate whether Gro is part of a stable multiprotein complex in the nucleus. Our results indicate that Gro does not form stable associations with other proteins but that it may be able to assemble into homomultimeric complexes.
Mol Cell Biol 1999 Mar
PMID:A conserved motif in goosecoid mediates groucho-dependent repression in Drosophila embryos. 1002 95

Differential display is an easily applied method for comparing gene expression in a variety of systems. We used a nonradioactive differential display technique to analyze X-ray-induced lymphomas derived from Emu-pim-1 transgenic and nontransgenic mice. Fragments of 11 differentially regulated genes were identified, three of which are novel sequences. One of the cloned fragments contained sequences of a mouse VL30 retroelement that was significantly overexpressed in a subset of lymphomas as compared with non-lymphomatous tissue. Interestingly, these lymphomas also displayed high levels of c-myc transcripts. An altered expression pattern of a glutathione S-transferase homologue was identified in several lymphomas. Moreover, a cytotoxic T-lymphocyte lipase appeared to be overexpressed specifically in lymphoma-containing spleen tissue, and the results suggest that it may be related to the endogenous immune response against lymphoma development.
Mol Carcinog 1999 Jan
PMID:Differentially expressed transcripts in X-ray-induced lymphomas identified by dioxygenin-labeled differential display. 1002 8


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