Millipore Sigma Vibrant Logo
 

lipid+signaling


225 Results Advanced Search  
Showing
Products (1)
Documents (214)
Site Content (10)
Can't Find What You're Looking For?
Contact Customer Service

 

  • Brain lipid binding protein in axon-Schwann cell interactions and peripheral nerve tumorigenesis. 12612091

    Loss of axonal contact characterizes Schwann cells in benign and malignant peripheral nerve sheath tumors (MPNST) from neurofibromatosis type 1 (NF1) patients. Tumor Schwann cells demonstrate NF1 mutations, elevated Ras activity, and aberrant epidermal growth factor receptor (EGFR) expression. Using cDNA microarrays, we found that brain lipid binding protein (BLBP) is elevated in an EGFR-positive subpopulation of Nf1 mutant mouse Schwann cells (Nf1(-/-) TXF) that grows away from axons; BLBP expression was not affected by farnesyltransferase inhibitor, an inhibitor of H-Ras. BLBP was also detected in EGFR-positive cell lines derived from Nf1:p53 double mutant mice and human MPNST. BLBP expression was induced in normal Schwann cells following transfection with EGFR but not H-Ras12V. Furthermore, EGFR-mediated BLBP expression was not inhibited by dominant-negative H-Ras, indicating that BLBP expression is downstream of Ras-independent EGFR signaling. BLBP-blocking antibodies enabled process outgrowth from Nf1(-/-) TXF cells and restored interaction with axons, without affecting cell proliferation or migration. Following injury, BLBP expression was induced in normal sciatic nerves when nonmyelinating Schwann cells remodeled their processes. These data suggest that BLBP, stimulated by Ras-independent pathways, regulates Schwann cell-axon interactions in normal peripheral nerve and peripheral nerve tumors.
    Document Type:
    Reference
    Product Catalog Number:
    AB1554
    Product Catalog Name:
    Anti-Nerve Growth Factor Receptor Antibody, p75

  • Lipid phosphate phosphatase-2 activity regulates S-phase entry of the cell cycle in Rat2 fibroblasts. 16467304

    Lipid phosphates are potent mediators of cell signaling and control processes including development, cell migration and division, blood vessel formation, wound repair, and tumor progression. Lipid phosphate phosphatases (LPPs) regulate the dephosphorylation of lipid phosphates, thus modulating their signals and producing new bioactive compounds both at the cell surface and in intracellular compartments. Knock-down of endogenous LPP2 in fibroblasts delayed cyclin A accumulation and entry into S-phase of the cell cycle. Conversely, overexpression of LPP2, but not a catalytically inactive mutant, caused premature S-phase entry, accompanied by premature cyclin A accumulation. At high passage, many LPP2 overexpressing cells arrested in G(2)/M and the rate of proliferation declined severely. This was accompanied by changes in proteins and lipids characteristic of senescence. Additionally, arrested LPP2 cells contained decreased lysophosphatidate concentrations and increased ceramide. These effects of LPP2 activity were not reproduced by overexpression or knock-down of LPP1 or LPP3. This work identifies a novel and specific role for LPP2 activity and bioactive lipids in regulating cell cycle progression.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple

  • Lipid rafts identified as locations of ectodomain shedding mediated by Meltrin beta/ADAM19. 15030395

    Meltrin beta (Mel beta, also called ADAM19) is a member of the ADAM (adisintegrin and metalloprotease) family, which are membrane-anchored glycoproteins that play crucial roles in various biological processes. Many intercellular signaling molecules are membrane-anchored proteins, which are proteolytically processed after becoming membrane-bound, to liberate their extracellular domains (ectodomain shedding). Genetic and biochemical studies have shown that some ADAMs participate in these events. We found previously that Mel beta can cleave the extracellular region of the membrane-anchored beta-exon-containing Neuregulin-1 (NRG beta1) protein, which is one of the main ligands for the neural ErbB receptor. Mel beta-deficient mice showed developmental defects in the nervous system. These observations raise the possibility that the NRG ectodomain shedding mediated by Mel beta is closely related to the neural development. Here we show that Mel beta-mediated ectodomain shedding of NRG beta1 takes place in the lipid rafts of neurons. The lipid rafts localization of Mel beta requires its membrane-anchoring region, and NRG beta1 ectodomain shedding is not enhanced if Mel beta cannot reach the lipid rafts. These results indicate that localization of Mel beta in lipid rafts is critical for its ectodomain shedding.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. 12716933

    Cholesterol/sphingolipid microdomains (lipid rafts) in the membrane are involved in protein trafficking, formation of signaling complexes, and regulation of actin cytoskeleton. Here, we show that lipid rafts exist abundantly in dendrites of cultured hippocampal neurons, in which they are associated with several postsynaptic proteins including surface AMPA receptors. Depletion of cholesterol/sphingolipid leads to instability of surface AMPA receptors and gradual loss of synapses (both inhibitory and excitatory) and dendritic spines. The remaining synapses and spines in raft-depleted neurons become greatly enlarged. The importance of lipid rafts for normal synapse density and morphology could explain why cholesterol promotes synapse maturation in retinal ganglion cells (Mauch et al., 2001) and offers a potential link between disordered cholesterol metabolism and the synapse loss seen in neurodegenerative disease.
    Document Type:
    Reference
    Product Catalog Number:
    MAB341
    Product Catalog Name:
    Anti-GABA A Receptor β 2,3 Chain Antibody, clone BD17

  • Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering. 16672658

    Agrin, a motoneuron-derived factor, and the muscle-specific receptor tyrosine kinase (MuSK) are essential for the acetylcholine receptor (AChR) clustering at the postjunctional membrane. However, the underlying signaling mechanisms remain poorly defined. We show that agrin stimulates a dynamic translocation of the AChR into lipid rafts-cholesterol and sphingolipid-rich microdomains in the plasma membrane. This follows MuSK partition into lipid rafts and requires its activation. Disruption of lipid rafts inhibits MuSK activation and downstream signaling and AChR clustering in response to agrin. Rapsyn, an intracellular protein necessary for AChR clustering, is located constitutively in lipid rafts, but its interaction with the AChR is inhibited when lipid rafts are perturbed. These results reveal that lipid rafts may regulate AChR clustering by facilitating the agrin/MuSK signaling and the interaction between the receptor and rapsyn, both necessary for AChR clustering and maintenance. These results provide insight into mechanisms of AChR cluster formation.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Lipid mixtures containing a very high proportion of saturated fatty acids only modestly impair insulin signaling in cultured muscle cells. 25793412

    In vitro examinations of the effect of saturated fatty acids on skeletal muscle insulin action often use only one or two different fatty acid species, which does not resemble the human plasma fatty acid profile. We compared graded concentrations (0.1-0.8 mM) of 3 different lipid mixtures: 1) a physiologic fatty acid mixture (NORM; 40% saturated fatty acids), 2) a physiologic mixture high in saturated fatty acids (HSFA; 60% saturated fatty acids), and 3) 100% palmitate (PALM) on insulin signaling and fatty acid partitioning into triacylglycerol (TAG) and diacylglycerol (DAG) in cultured muscle cells. As expected, PALM readily impaired insulin-stimulated pAktThr308/Akt and markedly increased intracellular DAG content. In contrast, the fatty acid mixtures only modestly impaired insulin-stimulated pAktThr308M/Akt, and we found no differences between NORM and HSFA. Importantly, NORM and HSFA did not increase DAG content, but instead dose-dependently increased TAG accumulation. Therefore, the robust impairment in insulin signaling found with palmitate exposure was attenuated with physiologic mixtures of fatty acids, even with a very high proportion of saturated fatty acids. This may be explained in part by selective partitioning of fatty acids into neutral lipid (i.e., TAG) when muscle cells were exposed to physiologic lipid mixtures.
    Document Type:
    Reference
    Product Catalog Number:
    ABS54
    Product Catalog Name:
    Anti-AS160 Antibody

  • Lipid rafts remodeling in estrogen receptor-negative breast cancer is reversed by histone deacetylase inhibitor. 16505096

    Recently, we have found dramatic overexpression of ecto-5'-nucleotidase (or CD73), a glycosylphosphatidylinositol-anchored component of lipid rafts, in estrogen receptor-negative [ER-] breast cancer cell lines and in clinical samples. To find out whether there is a more general shift in expression profile of membrane proteins, we undertook an investigation on the expression of selected membrane and cytoskeletal proteins in aggressive and metastatic breast cancer cells. Our analysis revealed a remarkably uniform shift in expression of a broad range of membrane, cytoskeletal, and signaling proteins in ER- cells. A similar change was found in two in vitro models of transition to ER- breast cancer: drug-resistant Adr2 and c-Jun-transformed clones of MCF-7 cells. Interestingly, similar expression pattern was observed in normal fibroblasts, suggesting the commonality of membrane determinants of invasive cancer cells with normal mesenchymal phenotype. Because a number of investigated proteins are components of lipid rafts, our results suggest that there is a major remodeling of lipid rafts and underlying cytoskeleton in ER- breast cancer. To test whether this broadly defined ER- phenotype could be reversed by treatment with differentiating agent, we treated ER- cells with trichostatin A, an inhibitor of histone deacetylase, and observed reversal of mesenchymal and reappearance of epithelial markers. Changes in gene and protein expression also included increased capacity to generate adenosine and altered expression profile of adenosine receptors. Thus, our results suggest that during transition to invasive breast cancer there is a significant structural reorganization of lipid rafts and underlying cytoskeleton that is reversed upon histone deacetylase inhibition.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Lipid rafts are required for GLUT4 internalization in adipose cells. 11593015

    It has been recently reported that insulin recruits a novel signaling machinery to lipid rafts required for insulin-stimulated GLUT4 translocation [Baumann, A., Ribon, V., Kanzaki, M., Thurmond, D. C., Mora, S., Shigematsu, S., Bickel, P. E., Pessin, J. E. & Saltiel, A. R. (2001) Nature 407, 202-207, 2000; Chiang, S. H., Baumann, C. A., Kanzaki, M., Thurmond, D. C., Watson, R. T., Neudauer, C. L., Macara, I. G., Pessin, J. E. & Saltiel, A. R. (2001) Nature 410, 944-948]. We have assessed the role of lipid rafts on GLUT4 traffic in adipose cells. High GLUT4 levels were detected in caveolae from adipocytes by two approaches, the mechanical isolation of purified caveolae from plasma membrane lawns and the immunogold analysis of plasma membrane lawns followed by freeze-drying. The role of lipid rafts in GLUT4 trafficking was studied by adding nystatin or filipin at concentrations that specifically disrupt caveolae morphology and inhibit caveolae function without altering clathrin-mediated endocytosis. These caveolae inhibitors did not affect the insulin-stimulated glucose transport. However, they blocked both the GLUT4 internalization and the down-regulation of glucose transport triggered by insulin removal in 3T3-L1 adipocytes. Our data indicate that lipid rafts are crucial for GLUT4 internalization after insulin removal. Given that high levels of GLUT4 were detected in caveolae from insulin-treated adipose cells, this transporter may be internalized from caveolae or caveolae may operate as an obligatory transition station before internalization.
    Document Type:
    Reference
    Product Catalog Number:
    14-864
    Product Catalog Name:
    PAK-1 PBD Protein (agarose free), 300 µg

  • Coordination of lipid droplet-associated proteins during the transition period of Holstein dairy cows. 21426973

    Dairy cows often experience negative energy balance with the onset of lactation, and severe or prolonged negative energy balance can contribute to declines in overall fitness. Energy stores, in the form of adipose tissue triacylglycerides, are mobilized during times of energy deficit, and recent research has implicated several proteins associated with the lipid droplet as lipolytic regulators. The objective of this study was to determine if these novel proteins associated with lipolytic regulation are altered with the changing metabolic demands of lactation. Weekly blood samples were collected from 26 Holstein cows from 21 d before expected parturition through 28 d postpartum, and again at 150 d postpartum. Serum nonesterified fatty acids, glycerol, and β-hydroxybutyrate were measured. Energy balance was calculated from daily feed intake and milk yield, weekly body weight, and monthly milk component measurements. Adipose tissue biopsies were taken 21 d before expected parturition (-21 d) and at 5, 21, and 150 d postpartum. Semiquantitative Western blotting was used to measure abundance of hormone-sensitive lipase (HSL), phosphorylated HSL, perilipin, phosphorylated perilipin (PPLIN), adipose triglyceride lipase (ATGL), and comparative gene identity-58 (CGI-58). Abundance of ATGL was less at 5 and 21 d in milk (DIM) compared with -21 and 150 DIM, even though cows were in negative energy balance and experiencing increased rates of lipolysis in early lactation. In contrast, phosphorylated HSL and PPLIN increased with increasing lipolysis immediately after parturition. Additionally, PPLIN was negatively correlated with milk yield at 5, 21, and 150 d postpartum, and negatively correlated with feed intake and energy balance at 21 d postpartum. This result is consistent with the hypothesis that phosphorylation of perilipin is responsive to signals for increased triaclyglyceride mobilization. Finally, a consistent negative correlation between abundance of perilipin and CGI-58 proteins was observed throughout the transition period. These results confirm that novel lipolytic proteins in adipose tissue are regulated at the level of protein abundance and phosphorylation during the periparturient period and into mid lactation.Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
    Document Type:
    Reference
    Product Catalog Number:
    AB10200
    Product Catalog Name:
    Anti-Perilipin A Antibody

  • Inhibition of Lipid Signaling Enzyme Diacylglycerol Kinase {epsilon} Attenuates Mutant Huntingtin Toxicity. 22511757

    Huntington disease (HD) is a dominantly inherited neurodegenerative disease caused by a polyglutamine expansion in the protein huntingtin (Htt). Striatal and cortical neuronal loss are prominent features of this disease. No disease-modifying treatments have been discovered for HD. To identify new therapeutic targets in HD, we screened a kinase inhibitor library for molecules that block mutant Htt cellular toxicity in a mouse HD striatal cell model, Hdh(111Q/111Q) cells. We found that diacylglycerol kinase (DGK) inhibitor II (R59949) decreased caspase-3/7 activity after serum withdrawal in striatal Hdh(111Q/111Q) cells. In addition, R59949 decreased the accumulation of a 513-amino acid N-terminal Htt fragment processed by caspase-3 and blocked alterations in lipid metabolism during serum withdrawal. To identify the diacylglycerol kinase mediating this effect, we knocked down all four DGK isoforms expressed in the brain (β, γ, ε, and ζ) using siRNA. Only the knockdown of the family member, DGKε, blocked striatal Hdh(111Q/111Q)-mediated toxicity. We also investigated the significance of these findings in vivo. First, we found that reduced function of the Drosophila DGKε homolog significantly improves Htt-induced motor dysfunction in a fly model of HD. In addition, we find that the levels of DGKε are increased in the striatum of R6/2 HD transgenic mice when compared with littermate controls. Together, these findings indicate that increased levels of kinase DGKε contribute to HD pathogenesis and suggest that reducing its levels or activity is a potential therapy for HD.
    Document Type:
    Reference
    Product Catalog Number:
    MAB2166
    Product Catalog Name:
    Anti-Huntingtin Protein Antibody, a.a. 181-810, clone 1HU-4C8