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101.
102.
Inhibition of Chk1 by activated PKB/Akt 总被引:2,自引:0,他引:2
We have shown recently that DNA damage effector kinase Chk1 is phosphorylated in vitro by protein kinase B/Akt (PKB/Akt) on serine 280. Activation of Chk1 by DNA damage in vivo is suppressed in presence of activated PKB. In this study we show that Chk1 is phosphorylated by PKB in vivo, and that increased phosphorylation by PKB on serine 280 correlates with impairment of Chk1 activation by DNA damage. Our results indicate a likely mechanism for the negative effects that phosphorylation of serine 280 has on activation of Chk1. The Chk1 protein phosphorylated by PKB on serine 280 does not enter into protein complexes after replication arrest. Moreover, Chk1 phosphorylated by PKB fails to undergo activating phosphorylation on serine 345 by ATM/ATR. Phosphorylation by ATM/ATR and association with other checkpoint proteins are essential steps in activation of Chk1. Inhibition of these steps provides a plausible explanation for the observed attenuation of Chk1 activation by activated PKB after DNA damage. 相似文献
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Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes 总被引:11,自引:0,他引:11
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Chen J Anderson JB DeWeese-Scott C Fedorova ND Geer LY He S Hurwitz DI Jackson JD Jacobs AR Lanczycki CJ Liebert CA Liu C Madej T Marchler-Bauer A Marchler GH Mazumder R Nikolskaya AN Rao BS Panchenko AR Shoemaker BA Simonyan V Song JS Thiessen PA Vasudevan S Wang Y Yamashita RA Yin JJ Bryant SH 《Nucleic acids research》2003,31(1):474-477
Three-dimensional structures are now known within most protein families and it is likely, when searching a sequence database, that one will identify a homolog of known structure. The goal of Entrez's 3D-structure database is to make structure information and the functional annotation it can provide easily accessible to molecular biologists. To this end, Entrez's search engine provides several powerful features: (i) links between databases, for example between a protein's sequence and structure; (ii) pre-computed sequence and structure neighbors; and (iii) structure and sequence/structure alignment visualization. Here, we focus on a new feature of Entrez's Molecular Modeling Database (MMDB): Graphical summaries of the biological annotation available for each 3D structure, based on the results of automated comparative analysis. MMDB is available at: http://www.ncbi.nlm.nih.gov/Entrez/structure.html. 相似文献
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Pamidimukkala J Hay M 《American journal of physiology. Heart and circulatory physiology》2003,285(4):H1515-H1520
It is well established that the area postrema, as a circumventricular organ, is susceptible to modulation by circulating hormones and peptides. Furthermore, activation of the area postrema has been shown to modulate central neurons involved in the regulation of cardiovascular function and blood pressure. In particular, the vasoactive peptide angiotensin II (ANG II) has been shown to inhibit baroreflex regulation of heart rate and increase sympathetic outflow and blood pressure via activation of area postrema neurons. Estrogen is thought to protect against hypertension in both humans and animal models and has been shown in a number of systems to alter the effects of ANG II. The purpose of the present study was to determine the effects of estrogen on ANG II activation of area postrema neurons. In this study, the effects of ANG II and KCl on fura 2-measured cytosolic Ca2+ concentration ([Ca2+]i) responses in cultured area postrema neurons in the presence and absence of 12-h exposure to 100 nM 17 beta-estradiol (E2) were evaluated. In neurons incubated in control vehicle media, 50 nM ANG II increased [Ca2+]i by 92 +/- 12%. In neurons preincubated with 100 nM E2, ANG II increased [Ca2+]i by only 68 +/- 11%, for a total inhibition of the ANG II-evoked response of 24%. Coapplication of the estrogen receptor antagonist ICI-182,780 did not inhibit the effects of E2. In the same cells in which the effects of E2 on ANG II-evoked responses were tested, the effects of incubation in E on the depolarization-induced increased [Ca2+2]i due to 60 mM KCl were also tested. Incubation of the cells with 100 nM E increased the KCl-evoked [Ca2+2]i response, and this response was blocked by ICI-182,780. These results suggest that in the area postrema, estrogen may utilize multiple pathways to modulate neural activity and responses to ANG II. 相似文献
107.
Two manipulative experiments tested hypotheses pertaining to the correlative control exerted by nodal roots on branch development of the distal non-rooted portion of Trifolium repens growing clonally under near-optimal conditions. The two experiments, differing in their pattern of excision to manipulate the number of branches formed at the first 9-10 phytomers distal to the youngest nodal root, each found that after 20 phytomers of growth the total number of lateral branches formed on the primary stolon remained between five and seven regardless of where the branches formed along the stolon. Additional treatments established that nodal roots influenced branch development via relationships among shoot sinks for the root-supplied resources rather than through variation in the supply of such resources induced by fluctuations in photosynthate supply to roots from branches. Regression analysis of data pooled from treatments of both experiments confirmed that shoot-sink relationships for root- supplied resources controlled the branching processes on the non-rooted portion of plants. A disbudding treatment, which removed all the apical and axillary buds present on basal branches, but left other branch tissues intact, increased branch development of the apical region in the same way as did complete excision of the basal lateral branches. The apical buds and the elongation processes occurring immediately proximal to the buds were thus identified as strong sinks for the root-supplied resources. Such results suggest that branch development on the non-rooted shoot portion distal to the youngest nodal root is regulated by competition among sinks for root-derived resources, of limited availability, necessary for the processes of elongation of axillary buds and the primary stolon apical bud. 相似文献
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Role of two residues proximal to the active site of Ubc9 in substrate recognition by the Ubc9.SUMO-1 thiolester complex 总被引:2,自引:0,他引:2
The small ubiquitin-like modifier SUMO-1 is covalently attached to lysine residues on target proteins by a specific conjugation pathway involving the E1 enzyme SAE1/SAE2 and the E2 enzyme Ubc9. In an ATP-dependent manner, the C-terminus of SUMO-1 forms consecutive thiolester bonds with cysteine residues in the SAE2 subunit and Ubc9, before the Ubc9.SUMO-1 thiolester complex catalyzes the formation of an isopeptide bond between SUMO-1 and the epsilon-amino group of the target lysine residue on the protein substrate. The SUMO-1 conjugation pathway bears many similarities with that of ubiquitin and other ubiquitin-like protein modifiers (Ubls), and because of its production of a singly conjugated substrate and the lack of absolute requirement in vitro for E3 enzymes, the SUMO-1/Ubc9 system is a good model for the analysis of protein conjugation pathways that share this basic chemistry. Here we describe methods of both steady-state and half-reaction kinetic analysis of Ubc9, and use these techniques to determine the role of two residues, Asp(100) and Lys(101) of Ubc9 which are not found in E2 enzymes from other protein conjugation pathways. These residues are found close to the active site Cys in the tertiary structure of Ubc9, and although they are shown to inhibit the transesterification reaction from SAE1/SAE2, they are important for substrate recognition in the context of the thiolester complex with SUMO-1. 相似文献