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91.
A method for the comprehensive proteomic analysis of membrane proteins 总被引:23,自引:0,他引:23
We describe a method that allows for the concurrent proteomic analysis of both membrane and soluble proteins from complex membrane-containing samples. When coupled with multidimensional protein identification technology (MudPIT), this method results in (i) the identification of soluble and membrane proteins, (ii) the identification of post-translational modification sites on soluble and membrane proteins, and (iii) the characterization of membrane protein topology and relative localization of soluble proteins. Overlapping peptides produced from digestion with the robust nonspecific protease proteinase K facilitates the identification of covalent modifications (phosphorylation and methylation). High-pH treatment disrupts sealed membrane compartments without solubilizing or denaturing the lipid bilayer to allow mapping of the soluble domains of integral membrane proteins. Furthermore, coupling protease protection strategies to this method permits characterization of the relative sidedness of the hydrophilic domains of membrane proteins. 相似文献
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Martin-Didonet CC Chubatsu LS Souza EM Kleina M Rego FG Rigo LU Yates MG Pedrosa FO 《Journal of bacteriology》2000,182(14):4113-4116
Azospirillum species are plant-associated diazotrophs of the alpha subclass of Proteobacteria. The genomes of five of the six Azospirillum species were analyzed by pulsed-field gel electrophoresis. All strains possessed several megareplicons, some probably linear, and 16S ribosomal DNA hybridization indicated multiple chromosomes in genomes ranging in size from 4.8 to 9.7 Mbp. The nifHDK operon was identified in the largest replicon. 相似文献
97.
Brown A Yates PA Burrola P Ortuño D Vaidya A Jessell TM Pfaff SL O'Leary DD Lemke G 《Cell》2000,102(1):77-88
Topographic maps are a fundamental feature of sensory representations in nervous systems. The formation of one such map, defined by the connection of ganglion cells in the retina to their targets in the superior colliculus of the midbrain, is thought to depend upon an interaction between complementary gradients of retinal EphA receptors and collicular ephrin-A ligands. We have tested this hypothesis by using gene targeting to elevate EphA receptor expression in a subset of mouse ganglion cells, thereby producing two intermingled ganglion cell populations that express distinct EphA receptor gradients. We find that these two populations form separate maps in the colliculus, which can be predicted as a function of the net EphA receptor level that a given ganglion cell expresses relative to its neighbors. 相似文献
98.
Proteomic tools for cell biology 总被引:2,自引:0,他引:2
Acquisition of large bodies of genomic sequence is facilitating the use of global techniques to assay cellular function. DNA microarrays have enabled the measurement of global mRNA levels and are able to detect changes in gene expression between different cellular states. Since much of the regulation of physiolgical processes happens post-translationally, measuring only the mRNA levels gives an incomplete picture. Strategies to assay global expression, localization, or interaction of proteins fall into the emerging field of proteomics, with various combinations of techniques being utilized to separate and identify proteins. In this review, we will present a general overview of the currently available proteomic tools and then give examples of how these tools are being utilized to answer questions in cell biology. 相似文献
99.
Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases 总被引:7,自引:0,他引:7
Hefner Y Borsch-Haubold AG Murakami M Wilde JI Pasquet S Schieltz D Ghomashchi F Yates JR Armstrong CG Paterson A Cohen P Fukunaga R Hunter T Kudo I Watson SP Gelb MH 《The Journal of biological chemistry》2000,275(48):37542-37551
We have previously reported that in thrombin-stimulated human platelets, cytosolic phospholipase A(2) (cPLA2) is phosphorylated on Ser-505 by p38 protein kinase and on Ser-727 by an unknown kinase. Pharmacological inhibition of p38 leads to inhibition of cPLA2 phosphorylation at both Ser-505 and Ser-727 suggesting that the kinase responsible for phosphorylation on Ser-727 is activated in a p38-dependent pathway. By using Chinese hamster ovary, HeLa, and HEK293 cells stably transfected with wild type and phosphorylation site mutant forms of cPLA2, we show that phosphorylation of cPLA2 at both Ser-505 and Ser-727 and elevation of Ca(2+) leads to its activation in agonist-stimulated cells. The p38-activated protein kinases MNK1, MSK1, and PRAK1 phosphorylate cPLA2 in vitro uniquely on Ser-727 as shown by mass spectrometry. Furthermore, MNK1 and PRAK1, but not MSK1, is present in platelets and undergo modest activation in response to thrombin. Expression of a dominant negative form of MNK1 in HEK293 cells leads to significant inhibition of cPLA2-mediated arachidonate release. The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727. 相似文献
100.
Bremner JB Coban B Griffith R Groenewoud KM Yates BF 《Bioorganic & medicinal chemistry》2000,8(1):201-214
Alpha1 adrenoceptors have three subtypes and drugs interacting selectively with these subtypes could be useful in the treatment of a variety of diseases. In order to gain an insight into the structural principles governing subtype selectivity, ligand based drug design (pharmacophore development) methods have been used to design a novel 1,2,3-thiadiazole ring D analogue of the aporphine system. Synthesis and testing of this compound as a ligand on cloned and expressed human alpha1 adrenoceptors is described. Low binding affinity was found, possibly due to an unfavourable electrostatic potential distribution. Pharmacophore models for antagonists at the three adrenoceptor sites (alpha1A, alpha1B, alpha1D) were generated from a number of different training sets and their value for the design of new selective antagonists discussed. The first preliminary antagonist pharmacophore model for the alpha1D adrenoceptor subtype is also reported. 相似文献