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A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation 总被引:1,自引:0,他引:1
Erickson JR Joiner ML Guan X Kutschke W Yang J Oddis CV Bartlett RK Lowe JS O'Donnell SE Aykin-Burns N Zimmerman MC Zimmerman K Ham AJ Weiss RM Spitz DR Shea MA Colbran RJ Mohler PJ Anderson ME 《Cell》2008,135(3):462-474
tRNAs are synthesized as immature precursors, and on their way to functional maturity, extra nucleotides at their 5' ends are removed by an endonuclease called RNase P. All RNase P enzymes characterized so far are composed of an RNA plus one or more proteins, and tRNA 5' end maturation is considered a universal ribozyme-catalyzed process. Using a combinatorial purification/proteomics approach, we identified the components of human mitochondrial RNase P and reconstituted the enzymatic activity from three recombinant proteins. We thereby demonstrate that human mitochondrial RNase P is a protein enzyme that does not require a trans-acting RNA component for catalysis. Moreover, the mitochondrial enzyme turns out to be an unexpected type of patchwork enzyme, composed of a tRNA methyltransferase, a short-chain dehydrogenase/reductase-family member, and a protein of hitherto unknown functional and evolutionary origin, possibly representing the enzyme's metallonuclease moiety. Apparently, animal mitochondria lost the seemingly ubiquitous RNA world remnant after reinventing RNase P from preexisting components. 相似文献
124.
Alyson R. Pierick Melissa McKane Kuo-Kuang Wen Heather L. Bartlett 《Journal of visualized experiments : JoVE》2014,(89)
Mutations in actin cause a range of human diseases due to specific molecular changes that often alter cytoskeletal function. In this study, imaging of fluorescently tagged proteins using total internal fluorescence (TIRF) microscopy is used to visualize and quantify changes in cytoskeletal dynamics. TIRF microscopy and the use of fluorescent tags also allows for quantification of the changes in cytoskeletal dynamics caused by mutations in actin. Using this technique, quantification of cytoskeletal function in live cells valuably complements in vitro studies of protein function. As an example, missense mutations affecting the actin residue R256 have been identified in three human actin isoforms suggesting this amino acid plays an important role in regulatory interactions. The effects of the actin mutation R256H on cytoskeletal movements were studied using the yeast model. The protein, Aip1, which is known to assist cofilin in actin depolymerization, was tagged with green fluorescent protein (GFP) at the N-terminus and tracked in vivo using TIRF microscopy. The rate of Aip1p movement in both wild type and mutant strains was quantified. In cells expressing R256H mutant actin, Aip1p motion is restricted and the rate of movement is nearly half the speed measured in wild type cells (0.88 ± 0.30 μm/sec in R256H cells compared to 1.60 ± 0.42 μm/sec in wild type cells, p < 0.005). 相似文献
125.
Jalan-Sakrikar N Bartlett RK Baucum AJ Colbran RJ 《The Journal of biological chemistry》2012,287(19):15275-15283
Protein-protein interactions are thought to modulate the efficiency and specificity of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) signaling in specific subcellular compartments. Here we show that the F-actin-binding protein α-actinin targets CaMKIIα to F-actin in cells by binding to the CaMKII regulatory domain, mimicking CaM. The interaction with α-actinin is blocked by CaMKII autophosphorylation at Thr-306, but not by autophosphorylation at Thr-305, whereas autophosphorylation at either site blocks Ca(2+)/CaM binding. The binding of α-actinin to CaMKII is Ca(2+)-independent and activates the phosphorylation of a subset of substrates in vitro. In intact cells, α-actinin selectively stabilizes CaMKII association with GluN2B-containing glutamate receptors and enhances phosphorylation of Ser-1303 in GluN2B, but inhibits CaMKII phosphorylation of Ser-831 in glutamate receptor GluA1 subunits by competing for activation by Ca(2+)/CaM. These data show that Ca(2+)-independent binding of α-actinin to CaMKII differentially modulates the phosphorylation of physiological targets that play key roles in long-term synaptic plasticity. 相似文献
126.
Jae J. Song Joo-Hang Kim Bo K. Sun Marco A. Alcala David L. Bartlett Yong J. Lee 《Cellular signalling》2010,22(3):377-385
We have previously observed that TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces acquired TRAIL resistance by increasing Akt phosphorylation and Bcl-xL expression. In this study, we report that Src, c-Cbl, and PI3K are involved in the phosphorylation of Akt during TRAIL treatment. Data from immunoprecipitation and immunoblotting assay reveal that Src interacts with c-Cbl and PI3K. Data from immune complex kinase assay demonstrate that Src can directly phosphorylate c-Cbl and PI3K p85 subunit protein. Data from gene knockdown experiments with an RNA interference (RNAi) technique show that c-Cbl is involved in the interaction between Src and PI3K p85 during TRAIL treatment, playing an important role in TRAIL-induced Akt phosphorylation. Taken together, c-Cbl may act as a mediator to regulate the Src-PI3K-Akt signal transduction pathway during TRAIL treatment. 相似文献
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128.
Sarwer DB LaRossa D Bartlett SP Low DW Bucky LP Whitaker LA 《Plastic and reconstructive surgery》2003,112(1):83-90
This study investigated the body image concerns of women who sought cosmetic breast augmentation. Thirty breast augmentation candidates completed several measures of body image before their initial surgical consultation. Thirty physically similar women who were not interested in breast augmentation were recruited from the medical center and university community and also completed the measures. Breast augmentation candidates, as compared with women not seeking augmentation, reported greater dissatisfaction with their breasts. Augmentation candidates rated their ideal breast size, as well as the breast size preferred by women, as significantly larger than did controls. In addition, women interested in breast augmentation reported greater investment in their appearance, greater distress about their appearance in a variety of situations, and more frequent teasing about their appearance. Finally, breast augmentation candidates also reported more frequent use of psychotherapy in the year before the operation as compared with women not seeking augmentation. These results replicate and extend previous studies of body image in cosmetic surgery patients. 相似文献
129.
Effect of pH, Protein Concentration, and Ionic Strength on Heat Inactivation of Staphylococcal Enterotoxin B 总被引:1,自引:2,他引:1 下载免费PDF全文
Heat treatment of highly purified staphylococcal enterotoxin B causes a more rapid loss of immunological activity at 70 to 80 C than at 90 to 100 C. Toxicological results based on intravenous injection of dogs paralleled the results obtained by immunological means (single gel diffusion). The loss of immunological activity did not follow first-order kinetics. Results are given on the effects on heat inactivation of changing pH, ionic strength, and initial concentration of enterotoxin. Disc-gel electrophoresis of purified enterotoxin B showed a major and minor band. The minor band was a size isomer of the major band. 相似文献
130.
L J Block J M Bartlett J Bolt-de Vries A P Themmen A O Brinkmann G F Weinbauer E Nieschlag J A Grootegoed 《The Journal of steroid biochemistry and molecular biology》1991,40(1-3):343-347
Adult rats were treated with ethane dimethane sulphonate (EDS), an agent that destroys Leydig cells. Within 5 days after EDS treatment, the levels of testosterone (T) in the circulation and in the testis were decreased to very low values, which makes it possible to manipulate the testicular T concentration through administration of exogenous T. Spermatogenesis was not markedly affected within 5 days after EDS treatment, also not in the absence of T administration. In testes of EDS-treated rats, the androgen receptor mRNA (ARmRNA) level remained unaltered for 5 days. In ventral prostate, however, this treatment caused a pronounced upregulation of the level of ARmRNA, which could be counteracted by implantation of silastic T implants immediately after EDS treatment. In EDS-treated rats carrying a T implant and in untreated rats, the same number of specific [3H]R1881 binding sites was observed using a total testis nuclear fraction (Scatchard analysis). In testes from EDS-treated rats without T implants, androgen receptors (AR) did not fractionate into the nuclear fraction; however, the total testicular AR content in these animals (measured by nuclear [3H]R1881 binding after receptor transformation through injection of a high dose of T, 2 h before killing the rats) remained unaltered. Immunoprecipitation and Western blotting using anti N-terminal antibodies seemed to indicate that the total testicular amount of AR protein in the EDS-treated rats was very low as compared to that in EDS-treated rats carrying T implants and in untreated rats. Even after receptor retransformation (by injection of a high dose of T) the receptors were not quantitatively detected by immunoprecipitation and Western blotting. This may point to a structural modification of the AR that occurs in the prolonged absence of androgens. 相似文献