Publications
211 results found
Chang SC, Mulloy B, Magee AI, 2011, Two distinct sites in sonic hedgehog combine for heparan sulfate interactions and cell signaling functions, Journal of Biological Chemistry
Hedgehog (Hh) proteins are morphogens that mediate many developmental processes. Hh signaling is significant for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. Hh proteins require heparan sulfate proteoglycans (HSPGs) for their normal distribution and signaling activity. Here we have used molecular modelling to examine the heparin-binding domain of Shh. In biochemical and cell biological assays the importance of specific residues of the putative heparin-binding domain for signaling were assessed. It was determined that key residues in hShh involved in heparin and HSPG syndecan-4 binding and biological activity included the well known cationic Cardin-Weintraub motif (lysine 32-lysine38), but also a previously unidentified major role for lysine 178. The activity of Shh mutated in these residues was tested by quantitation of alkaline phosphatase activity in C3H10T1/2 cells differentiating into osteoblasts and hShh-inducible gene expression in PANC1 human pancreatic ductal adenocarcinoma (PDAC) cells. Mutated hShhs such as K37/38S, K178S and particularly K37/38/178S that could not interact with heparin efficiently had reduced signaling activity compared to wild type hShh or a control mutation (K74S). In addition, the mutant hShh proteins supported reduced proliferation and invasion of PANC1 cells compared with control hShh proteins, following endogenous hShh depletion by RNAi knockdown. The data correlated with reduced Shh multimerization where the K37/38 and/or K178 mutations were examined. These studies provide a new insight into the functional roles of hShh interactions with HSPGs, which may allow targeting this aspect of hShh biology in, for example, PDAC.
Zeidman R, Buckland G, Cebecauer M, et al., 2011, DHHC2 is a protein S-acyl transferase for Lck, Molecular Membrane Biology, Vol: 28, Pages: 473-486
Lck is a non-receptor tyrosine kinase of the Src family that is essential for T cell activation. Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. Reversible S-acylation of Lck is observed in vivo and may function as a control mechanism. Here we identify the DHHC family protein S-acyltransferase DHHC2 as an enzyme capable of palmitoylating of Lck in T cells. Reducing the DHHC2 level in Jurkat T cells using siRNA causes decreased Lck S-acylation and partial dislocation from membranes, and conversely overexpression of DHHC2 increases S-acylation of an Lck surrogate, LckN10-GFP. DHHC2 localizes primarily to the endoplasmic reticulum and Golgi apparatus suggesting that it is involved in S-acylation of newly-synthesized or recycling Lck involved in T cell signalling.
McGinty J, Talbot C, Owen D, et al., 2011, Fluorescence Lifetime Imaging Microscopy, Endoscopy and Tomography, Editors: Boas, Pitris, Ramanujam, ISBN: 1420090364
Miguel L, Owen DM, Lim C, et al., 2010, Primary human CD4<SUP>+</SUP> T cells have diverse levels of membrane lipid order that dictate their function, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 77-77, ISSN: 0019-2805
Owen DM, Gaus K, Magee AI, et al., 2010, Dynamic organization of lymphocyte plasma membrane: lessons from advanced imaging methods, IMMUNOLOGY, Vol: 131, Pages: 1-8, ISSN: 0019-2805
- Author Web Link
- Cite
- Citations: 24
Owen DM, Oddos S, Kumar S, et al., 2010, High plasma membrane lipid order imaged at the immunological synapse periphery in live T cells, MOLECULAR MEMBRANE BIOLOGY, Vol: 27, Pages: 178-189, ISSN: 0968-7688
- Author Web Link
- Cite
- Citations: 64
Talbot C, McGinty J, McGhee E, et al., 2010, Fluorescence Lifetime Imaging and Metrology for Biomedicine, Handbook of Photonics for Biomedical Science, ISBN: 978-1439806289
Cebecauer M, Spitaler M, Serge A, et al., 2010, Signalling complexes and clusters: functional advantages and methodological hurdles, JOURNAL OF CELL SCIENCE, Vol: 123, Pages: 309-320, ISSN: 0021-9533
- Author Web Link
- Cite
- Citations: 100
Cebecauer M, Owen DM, Markiewicz A, et al., 2009, Lipid order and molecular assemblies in the plasma membrane of eukaryotic cells, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 37, Pages: 1056-1060, ISSN: 0300-5127
- Author Web Link
- Cite
- Citations: 10
Serpente N, Marcozzi C, Roberts GA, et al., 2009, Extracellularly truncated desmoglein 1 compromises desmosomes in MDCK cells, MOLECULAR MEMBRANE BIOLOGY, Vol: 17, Pages: 175-183, ISSN: 0968-7688
- Author Web Link
- Cite
- Citations: 11
Breckenridge RA, Zuberi Z, Gomes J, et al., 2009, Overexpression of the transcription factor Hand1 causes predisposition towards arrhythmia in mice, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 47, Pages: 133-141, ISSN: 0022-2828
- Author Web Link
- Cite
- Citations: 22
Plaza-Menacho I, Mologni L, Sala E, et al., 2009, Sorafenib functions to potently suppress RET tyrosine kinase activity by direct enzymatic inhibition and promoting RET lysosomal degradation independent of proteasomal targeting (vol 282, pg 29230, 2007), JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 284, Pages: 16060-16060
Zeidman R, Jackson CS, Magee AI, 2009, Analysis of protein acylation., Curr Protoc Protein Sci, Vol: Chapter 14, Pages: Unit-14.2
Proteins can be acylated with a variety of fatty acids attached by different covalent bonds, influencing, among other things, their function and intracellular localization. This unit describes methods to analyze protein acylation, both levels of acylation and also the identification of the fatty acid and the type of bond present in the protein of interest. Protocols are provided for metabolic labeling of proteins with tritiated fatty acids, for exploitation of the differential sensitivity to cleavage of different types of bonds, in order to distinguish between them, and for thin-layer chromatography to separate and identify the fatty acids associated with proteins.
Magee AI, 2009, Editorial., Mol Membr Biol, Pages: 1-1, ISSN: 1464-5203
Zeidman R, Jackson CS, Magee AI, 2009, Protein acyl thioesterases (Review), MOLECULAR MEMBRANE BIOLOGY, Vol: 26, Pages: 32-41, ISSN: 0968-7688
- Author Web Link
- Open Access Link
- Cite
- Citations: 93
Chang S-C, Magee AI, 2009, Acyltransferases for secreted signalling proteins (Review), MOLECULAR MEMBRANE BIOLOGY, Vol: 26, Pages: 104-113, ISSN: 0968-7688
- Author Web Link
- Open Access Link
- Cite
- Citations: 40
Magee AI, 2009, Foreword: Protein acylation and microdomains in membrane function, MOLECULAR MEMBRANE BIOLOGY, Vol: 26, Pages: 3-4, ISSN: 0968-7688
- Author Web Link
- Cite
- Citations: 1
Talbot C, McGinty J, McGhee E, et al., 2008, High speed, optically sectioned fluorescence lifetime imaging utilizing time-gated nipkow disk or multifocal multiphoton time correlated single photon counting microscopy
We report two optically sectioned fluorescence lifetime systems that exhibit better signal to noise per unit time than conventional time correlated single photon counting systems. Both systems are applied to biologically relevant samples. ©2007 Optical Society of America.
Manning HB, Kennedy GT, Owen DM, et al., 2008, A compact, multidimensional spectrofluorometer exploiting supercontinuum generation, JOURNAL OF BIOPHOTONICS, Vol: 1, Pages: 494-505, ISSN: 1864-063X
- Author Web Link
- Cite
- Citations: 35
Lossi NS, Rolhion N, Magee AI, et al., 2008, The <i>Salmonella</i> SPI-2 effector SseJ exhibits eukaryotic activator-dependent phospholipase A and glycerophospholipid:: cholesterol acyltransferase activity, MICROBIOLOGY-SGM, Vol: 154, Pages: 2680-2688, ISSN: 1350-0872
- Author Web Link
- Open Access Link
- Cite
- Citations: 62
Barral DC, Cavallari M, McCormick PJ, et al., 2008, CD1a and MHC class I follow a similar endocytic recycling pathway, TRAFFIC, Vol: 9, Pages: 1446-1457, ISSN: 1398-9219
- Author Web Link
- Cite
- Citations: 60
Manning HB, Owen DM, Auksorius E, et al., 2007, Applications of rapid time-gated hyperspectral FLIM: Live cell imaging of membrane order and 6-D microscopy, ISSN: 1605-7422
We describe the characterisation of a hyperspectral fluorescence lifetime imaging microscope that exploits high-speed time-gated imaging technology and a tunable continuum source for 6-D fluorescence imaging. This line-scanning confocal microscope can record the full spectral-temporal (i.e. excitation-emission-lifetime) fluorescence matrix at each pixel in a three dimensional (x-y-z) sample. This instrument has been applied to biological samples including model membranes and live cells labelled with the phase-sensitive membrane dye di-4-ANEPPDHQ, for which significant variation of lifetime with emission wavelength is observed. © 2007 SPIE-OSA.
Grant DM, McGinty J, McGhee EJ, et al., 2007, High speed optically sectioned fluorescence lifetime imaging permits study of live cell signaling events, Optics Express, Vol: 15, Pages: 16656-16673
We present a time domain optically sectioned fluorescence lifetime imaging (FLIM) microscope developed for high-speed live cell imaging. This single photon excited system combines wide field parallel pixel detection with confocal sectioning utilizing spinning Nipkow disc microscopy. It can acquire fluorescence lifetime images of live cells at up to 10 frames per second (fps), permitting high-speed FLIM of cell dynamics and protein interactions with potential for high throughput cell imaging and screening applications. We demonstrate the application of this FLIM microscope to real-time monitoring of changes in lipid order in cell membranes following cholesterol depletion using cyclodextrin and to the activation of the small GTP-ase Ras in live cells using FRET. © 2007 Optical Society of America.
Grant DM, McGinty J, McGhee EJ, et al., 2007, High speed optically sectioned fluorescence lifetime imaging permits study of live cell signaling events, OPTICS EXPRESS, Vol: 15, Pages: 15656-15673, ISSN: 1094-4087
- Author Web Link
- Cite
- Citations: 65
Plaza-Menacho I, Mologni L, Sala E, et al., 2007, Sorafenib functions to potently suppress RET tyrosine kinase activity by direct enzymatic inhibition and promoting RET lysosomal degradation independent of proteasomal targeting, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 282, Pages: 29230-29240
- Author Web Link
- Cite
- Citations: 86
Magee T, 2007, Membrane lipid microdomains: Roles in signalling and disease and 3D chromatin, SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, Vol: 18, Pages: 571-572, ISSN: 1084-9521
Owen DM, Neil MAA, French PMW, et al., 2007, Optical techniques for imaging membrane lipid microdomains in living cells, SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, Vol: 18, Pages: 591-598, ISSN: 1084-9521
- Author Web Link
- Cite
- Citations: 34
Plaza-Menacho I, van der Sluis T, Hollema H, et al., 2007, Ras/ERK1/2-mediated STAT3 Ser<SUP>727</SUP> phosphorylation by familial medullary thyroid carcinoma-associated RET mutants induces full activation of STAT3 and is required for c-<i>fos</i> promoter activation, cell mitogenicity, and transformation, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 282, Pages: 6415-6424, ISSN: 0021-9258
- Author Web Link
- Cite
- Citations: 51
Leung KF, Baron R, Ali BR, et al., 2007, Rab GTPases containing a CAAX motif are processed post-geranylgeranylation by proteolysis and methylation, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 282, Pages: 1487-1497
- Author Web Link
- Cite
- Citations: 64
Gater DL, Seddon JM, Law RV, et al., 2007, Cholesterol-driven lamellar phases: The phase behaviour of fully hydrated mixtures of dipalmitoylglycerol and cholesterol, 51st Annual Meeting of the Biophysical-Society, Publisher: BIOPHYSICAL SOCIETY, Pages: 57A-57A, ISSN: 0006-3495
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.