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131.
132.
Nicholas?M?Chesarino Jocelyn?C?Hach James?L?Chen Balyn?W?Zaro Murugesan?VS?Rajaram Joanne?Turner Larry?S?Schlesinger Matthew?R?Pratt Howard?C?Hang Jacob?S?YountEmail author 《BMC biology》2014,12(1):91
Background
Palmitoylation is a 16-carbon lipid post-translational modification that increases protein hydrophobicity. This form of protein fatty acylation is emerging as a critical regulatory modification for multiple aspects of cellular interactions and signaling. Despite recent advances in the development of chemical tools for the rapid identification and visualization of palmitoylated proteins, the palmitoyl proteome has not been fully defined. Here we sought to identify and compare the palmitoylated proteins in murine fibroblasts and dendritic cells.Results
A total of 563 putative palmitoylation substrates were identified, more than 200 of which have not been previously suggested to be palmitoylated in past proteomic studies. Here we validate the palmitoylation of several new proteins including Toll-like receptors (TLRs) 2, 5 and 10, CD80, CD86, and NEDD4. Palmitoylation of TLR2, which was uniquely identified in dendritic cells, was mapped to a transmembrane domain-proximal cysteine. Inhibition of TLR2 S-palmitoylation pharmacologically or by cysteine mutagenesis led to decreased cell surface expression and a decreased inflammatory response to microbial ligands.Conclusions
This work identifies many fatty acylated proteins involved in fundamental cellular processes as well as cell type-specific functions, highlighting the value of examining the palmitoyl proteomes of multiple cell types. S-palmitoylation of TLR2 is a previously unknown immunoregulatory mechanism that represents an entirely novel avenue for modulation of TLR2 inflammatory activity.133.
Britten CJ; van den Eijnden DH; McDowell W; Kelly VA; Witham SJ; Edbrooke MR; Bird MI; de Vries T; Smithers N 《Glycobiology》1998,8(4):321-327
The alpha3 fucosyltransferase, FucT-VII, is one of the key
glycosyltransferases involved in the biosynthesis of the sialyl Lewis X
(sLex) antigen on human leukocytes. The sialyl Lewis X antigen
(NeuAcalpha(2-3)Galbeta(1-4)[Fucalpha(1-3)]GlcNAc-R) is an essential
component of the recruitment of leukocytes to sites of inflammation,
mediating the primary interaction between circulating leukocytes and
activated endothelium. In order to characterize the enzymatic properties of
the leukocyte alpha3 fucosyltransferase FucT-VII, the enzyme has been
expressed in Trichoplusia ni insect cells. The enzyme is capable of
synthesizing both sLexand sialyl-dimeric-Lexstructures in vitro , from
3'-sialyl-lacNAc and VIM-2 structures, respectively, with only low levels
of fucose transfer observed to neutral or 3'-sulfated acceptors. Studies
using fucosylated NeuAcalpha(2-3)-(Galbeta(1- 4)GlcNAc)3-Me acceptors
demonstrate that FucT-VII is able to synthesize both di-fucosylated and
tri-fucosylated structures from mono- fucosylated precursors, but
preferentially fucosylates the distal GlcNAc within a polylactosamine
chain. Furthermore, the rate of fucosylation of the internal GlcNAc
residues is reduced once fucose has been added to the distal GlcNAc. These
results indicate that FucT-VII is capable of generating complex selectin
ligands, in vitro , however the order of fucose addition to the lactosamine
chain affects the rate of selectin ligand synthesis.
相似文献
134.
Summary Soils derived from hydrothermally altered andesite support unique communities of Sierran conifers (Pinus ponderosa Laws. and P. jeffreyi Grev. and Balf.) amongst sagebrush (Artemisia tridentata Nutt.) vegetation in the western Great Basin. Plants grown in soil derived from hydrothermally altered bedrock had lower growth rates, total biomass, and net photosynthetic rates than plants grown in soil derived from unaltered andesite of the same formation. Total dry mass was 10 to 28% lower for conifers grown in altered soil whereas dry mass of Artemisia tridentata and Bromus tectorum L. was reduced by over 90%. Results from a nutrient amendment experiment indicated that low phosphorus was the dominant limitation in altered soil, and phosphorus-deficiency affected growth primarily by limiting leaf area development rather than direct inhibition of photosynthesis. The proportionately greater reduction of biomass for Artemisia and Bromus grown in altered soil supports our hypothesis that Great Basin vegetation is excluded from altered soil by intolerance to nutrient deficiency. The Sierran conifers growing on this rock type are therefore free of competition for water with Great Basin vegetation and are able to persist in an exceptionally dry climate. 相似文献
135.
Fatty acid binding to vesicular stomatitis virus glycoprotein: a new type of post-translational modification of the viral glycoprotein. 总被引:49,自引:0,他引:49
The glycoprotein (G) of vesicular stomatitis virus (VSV) binds 1–2 moles of fatty acid per mole of protein. The fatty acids cannot be released by repeated extractions of the protein with organic solvents, nor can they be released by denaturing the protein with ionic or nonionic detergents. Pronase digestion of G yields an organic extractable fragment that contains bound fatty acid. The fatty acid is quantitatively released from this fragment and from intact G by mild alkali treatment in methanol and is identified by gas-liquid and thin-layer chromatography as, predominantly, the methyl ester of palmitic acid. Insignificant amounts of phosphate are found in G, thus ruling out the presence of bound phospholipid. Chicken embryo fibroblast pre-labeled with 3H-palmitate and then infected with VSV for 4 hr show the presence of 3H label in G but not in other viral structural proteins. The 3H label is present only in the fatty acid moiety of the protein. Much smaller amounts of 3H fatty acid are bound to G protein formed by the VSV mutant ts045 grown at the nonpermissive temperature, and no 3H fatty acid is bound to G synthesized at 37°C in cells pretreated with tunicamycin, an inhibitor of glycosylation. However, infection with the VSV-Orsay strain at 30°C in the presence of tunicamycin allows for production of VSV particles with nonglycosylated G (Gibson, Schlesinger and Kornfeld, 1979), and this G has the same proportion of the fatty acid as does the normal glycosylated G. These data indicate that fatty acids become covalently attached to the G polypeptide chain during maturation of the protein—perhaps as the glycoprotein moves to the cell's plasma membrane. 相似文献
136.
E. S. Bernhardt J. J. Barber J. S. Pippen L. Taneva J. A. Andrews W. H. Schlesinger 《Biogeochemistry》2006,77(1):91-116
Emissions of CO2 from soils make up one of the largest fluxes in the global C cycle, thus small changes in soil respiration may have large
impacts on global C cycling. Anthropogenic additions of CO2 to the atmosphere are expected to alter soil carbon cycling, an important component of the global carbon budget. As part
of the Duke Forest Free-Air CO2 Enrichment (FACE) experiment, we examined how forest growth at elevated (+200 ppmv) atmospheric CO2 concentration affects soil CO2 dynamics over 7 years of continuous enrichment. Soil respiration, soil CO2 concentrations, and the isotopic signature of soil CO2 were measured monthly throughout the 7 years of treatment. Estimated annual rates of soil CO2 efflux have been significantly higher in the elevated plots in every year of the study, but over the last 5 years the magnitude
of the CO2 enrichment effect on soil CO2 efflux has declined. Gas well samples indicate that over 7 years fumigation has led to sustained increases in soil CO2 concentrations and depletion in the δ13C of soil CO2 at all but the shallowest soil depths. 相似文献
137.
Accelerated tree growth under elevatedatmospheric CO2 concentrations may influencenutrient cycling in forests by (i) increasingthe total leaf area, (ii) increasing the supplyof soluble carbohydrate in leaf tissue, and (iii) increasing nutrient-use efficiency. Here wereport the results of intensive sampling andlaboratory analyses of NH
4
+
, NO
3
–
, PO
4
3–
, H+, K+, Na+,Ca2+, Mg2+, Cl–, SO
4
2–
, and dissolved organic carbon (DOC) in throughfallprecipitation during the first 2.5+ years of the DukeUniversity Free-Air CO2 Enrichment (FACE)experiment. After two growing seasons, a largeincrease (i.e., 48%) in throughfall deposition of DOCand significant trends in throughfall volume and inthe deposition of NH
4
+
, NO
3
–
, H+, and K+ can be attributed to the elevatedCO2 treatment. The substantial increase indeposition of DOC is most likely associated withincreased availability of soluble C in plant foliage,whereas accelerated canopy growth may account forsignificant trends toward decreasing throughfallvolume, decreasing deposition of NH
4
+
,NO
3
–
, and H+, and increasing deposition of K+ under elevated CO2. Despiteconsiderable year-to-year variability, there wereseasonal trends in net deposition of NO
3
–
,H+, cations, and DOC associated with plant growthand leaf senescence. The altered chemical fluxes inthroughfall suggest that soil solution chemistry mayalso be substantially altered with continued increasesin atmospheric CO2 concentrations in the future. 相似文献
138.
A Nagler R Condiotti R Rabinowitz M Schlesinger M Nguyen LWMM Terstappen 《Cancer immunology, immunotherapy : CII》1999,16(3):177-187
Multi-parameter flow cytometry (MPFC) was used to detect minimal residual disease (MRD) following bone marrow transplantation
(BMT) in 21 patients. Bone marrow (BM) was analyzed pre-transplant and 3–4 months post-BMT while the patients were in clinical
and morphological remission. MRD was detected by identifying cells with aberrant antigen expression and/or leukemia-associated
phenotype (LAP) using MPFC. Prior to BMT, 8 out of 21 patients exhibited normal antigen expression based on normal BM samples
while 13 BM aspirates had abnormal MPFC. Pre-BMT MPFC was abnormal in all 10 patients who were not in complete remission (CR)
(>5% blasts in BM) as well as 3 patients acute lymphoblastic leukemia (ALL) who were in CR. In BM from ALL patients, an abnormal
uniform B cell population was observed however antigen expression patterns varied greatly between patients. BM from acute
myeloblastic leukemia (AML) patients showed an abnormal distribution of CD34+ cells. In addition, a correlation was observed
between pre-BMT cytogenetics and MPFC. Only 2 out of 8 (25%) patients with normal MPFC pre-autologous bone marrow transplantation
(ABMT) relapsed (AML), while 6 out of 13 (46%) patients with abnormal pre-BMT MPFC relapsed including 2 out of 3 patients
who were transplanted in clinical CR. Pre-BMT MPFC may thus be an effective tool for detection of MRD by detection of a pre-transplant
MPFC abnormality. 相似文献
139.
D J Krogstad S P Sutera J S Marvel I Y Gluzman C W Boylan J R Colca J R Williamson P H Schlesinger 《Blood cells》1991,17(1):229-41; discussion 242-8
In the studies reported here, we examined the role of calcium in the maturation of the human malaria parasite Plasmodium falciparum, and in the loss of red cell deformability associated with parasite maturation. P. falciparum alters the permeability of its host red cell, which normally maintains submicromolar cytoplasmic concentrations of calcium. Infection of the red cell and parasite maturation produce a 30-fold increase in calcium uptake. Both parasite maturation and the loss of red cell deformability are blocked by EGTA (by extracellular-free calcium concentrations less than or equal to 35 microM) and by other calcium antagonists. The loss of red cell deformability that occurs with parasite maturation is accompanied by alterations in the cytoskeletal proteins of parasitized red cells similar to those produced by the calcium ionophore A23187 (reductions in bands 2.1 [ankyrin], 4.1, and 5 [actin]). These results establish that parasite development and the loss of red cell deformability are calcium-dependent. They suggest that parasite-induced changes in the calcium permeability of the red cell activate endogenous transglutaminase activity by raising the free calcium concentration of the red cell cytoplasm. 相似文献
140.