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961.
Biomechanics and Modeling in Mechanobiology - Liquid–liquid phase separation has emerged as a fundamental mechanism underlying intracellular organization, with evidence for it being reported... 相似文献
962.
963.
Keren E. Shapira Tal Hirschhorn Lior Barzilay Nechama I. Smorodinsky Yoav I. Henis Marcelo Ehrlich 《Molecular biology of the cell》2014,25(10):1620-1628
Transforming growth factor-β (TGF-β) ligands activate Smad-mediated and noncanonical signaling pathways in a cell context–dependent manner. Localization of signaling receptors to distinct membrane domains is a potential source of signaling output diversity. The tumor suppressor/endocytic adaptor protein disabled-2 (Dab2) was proposed as a modulator of TGF-β signaling. However, the molecular mechanism(s) involved in the regulation of TGF-β signaling by Dab2 were not known. Here we investigate these issues by combining biophysical studies of the lateral mobility and endocytosis of the type I TGF-β receptor (TβRI) with TGF-β phosphoprotein signaling assays. Our findings demonstrate that Dab2 interacts with TβRI to restrict its lateral diffusion at the plasma membrane and enhance its clathrin-mediated endocytosis. Small interfering RNA–mediated knockdown of Dab2 or Dab2 overexpression shows that Dab2 negatively regulates TGF-β–induced c-Jun N-terminal kinase (JNK) activation, whereas activation of the Smad pathway is unaffected. Moreover, activation of JNK by TGF-β in the absence of Dab2 is disrupted by cholesterol depletion. These data support a model in which Dab2 regulates the domain localization of TβRI in the membrane, balancing TGF-β signaling via the Smad and JNK pathways. 相似文献
964.
965.
S N Zagrebel'ny? A I Zakabunin V A Korzhov N V Melamed O Iu Smirnova 《Bioorganicheskaia khimiia》1986,12(10):1329-1334
A hybrid beta-lactamase gene with a synthetic tuftsin-coding DNA fragment inserted at the Pst I-site of pBR322 plasmid has been obtained and its expression has been studied. Radioactive amino acids have been used to show that in E. coli chi 925 minicells up to 30% of newly synthesized chimeric protein is secreted into periplasm providing the tuftsin transport. After hybrid protein cleavage with CNBr, tuftsin has been isolated using ion-exchange and thin-layer chromatography. 相似文献
966.
Microfilament assembly is required for antigen-receptor-mediated activation of human B lymphocytes 总被引:6,自引:0,他引:6
I Melamed G P Downey K Aktories C M Roifman 《Journal of immunology (Baltimore, Md. : 1950)》1991,147(4):1139-1146
The mechanisms responsible for initiating the conversion of globular to filamentous actin (assembly) after stimulation of B lymphocytes and the role of these cytoskeletal changes in cell activation are incompletely understood. We investigated the molecular basis of the signals leading to actin polymerization and concentrated on the involvement of guanosine triphosphate (GTP)-binding regulatory proteins, and protein kinase C (PKC). In addition, we related these early events to later events in B-cell activation, including cell proliferation. Cross-linking the Ag receptor with Staphylococcus aureus Cowan I (SAC) or anti-IgM antibodies, or stimulation of PKC with phorbol ester induced a time- and concentration-dependent increase in the filamentous actin content of B cells. Inhibition or depletion of PKC resulted in decreased actin assembly induced by anti-IgM, SAC, and PMA, suggesting that the signal for polymerization is generated distally to PKC activation. Pertussis toxin pretreatment inhibited the responses to anti-IgM and SAC but not PMA, and direct stimulation of permeabilized cells with GTP gamma S induced microfilament assembly, indicating the involvement of a GTP-binding protein for receptor-mediated events. Disruption of actin polymerization with botulinum C2 toxin or cytochalasin D inhibited the assembly of actin and [3H]TdR incorporation induced by all stimuli. We conclude that human B cell activation by receptor-mediated stimuli results in actin polymerization by signaling pathways coupled to GTP-binding proteins. These changes in the cytoskeleton may be involved in the transduction of messages leading to responses such as proliferation in B lymphocytes. 相似文献
967.
968.
Tal Oron Avihu Krieger Michal Yakobovich-Gavan Ariel Tenenbaum Rotem Diamant Moshe Phillip Liora Lazar 《Endocrine practice》2022,28(1):36-43
ObjectiveGiven the large number of false-positive growth hormone deficiency (GHD) diagnoses from a single growth hormone (GH) stimulation test in children, 2 different pharmacologic tests, performed on separate days or sequentially, are required. This study aimed to assess the reliability and safety of a combined arginine-clonidine stimulation test (CACST).MethodsThis was a retrospective, single-center, observational study. During 2017-2019, 515 children aged >8 years underwent GH stimulation tests (CACST: n = 362 or clonidine stimulation test [CST]: n = 153). The main outcome measures used to compare the tests were GH response (sufficiency/deficiency) and amplitude and timing of peak GH and safety parameters.ResultsPopulation characteristics were as follows: median age of 12.2 years (interquartile range [IQR]: 10.7, 13.4), 331 boys (64%), and 282 prepubertal children (54.8%). The GHD rate was comparable with 12.7% for CACST and 14.4% for CST followed by a confirmatory test (glucagon or arginine) (P = .609). Peak GH was higher and occurred later in response to CACST compared with CST (14.6 ng/mL [IQR: 10.6, 19.4] vs 11.4 ng/mL [IQR: 7.0, 15.8], respectively, P < .001; 90 minutes [IQR: 60, 90] vs 60 minutes [IQR: 60, 90], respectively, P < .001). No serious adverse events occurred following CACST.ConclusionOur findings demonstrate the reliability and safety of CACST in detecting GHD in late childhood and adolescence, suggesting that it may replace separate or sequential GH stimulation tests. By diminishing the need for the second GH stimulation test, CACST saves time, is more cost-effective, and reduces discomfort for children, caregivers, and medical staff. 相似文献
969.
Dynamic Diversification from a Putative Common Ancestor of Scorpion Toxins Affecting Sodium, Potassium, and Chloride Channels 总被引:11,自引:1,他引:10
Oren Froy Tal Sagiv Michal Poreh Daniel Urbach Noam Zilberberg Michael Gurevitz 《Journal of molecular evolution》1999,48(2):187-196
Scorpions have survived successfully over millions of years without detectable changes in their morphology. Instead, they
have developed an efficient alomonal machinery and a stinging device supporting their needs for prey and defense. They produce
a large variety of polypeptidic toxins that bind and modulate ion channel conductance in excitable tissues. The binding site,
mode of action, and chemical properties of many toxins have been studied extensively, but little is known about their genomic
organization and diversity. Genes representing each of the major classes of Buthidae scorpion toxins, namely, ``long' toxins,
affecting sodium channels (alpha, depressant, and excitatory), and ``short' toxins, affecting potassium and chloride channels,
were isolated from a single scorpion segment and analyzed. Each toxin type was found to be encoded by a gene family. Regardless
of toxin length, 3-D structure, and site of action, all genes contain A+T-rich introns that split, at a conserved location,
an amino acid codon of the signal sequence. The introns vary in length and sequence but display identical boundaries, agree
with the GT/AG splice junctions, and contain T-runs downstream of a putative branch point, 5′-TAAT-3′. Despite little sequence
similarity among all toxin classes, the conserved gene organization, intron features, and common cysteine-stabilized α-helical
(CSH) core connecting an α-helix to a three-stranded β-sheet suggest, that they all evolved from an ancestral common progenitor.
Furthermore, the vast diversity found among genomic copies, cDNAs, and their protein products for each toxin suggests an extensive
evolutionary process of the scorpion ``pharmaceutical factory,' whose success is due, most likely, to the inherent permissiveness
of the toxin exterior to structural alterations.
Received: 16 March 1998 / Accepted: 30 July 1998 相似文献
970.