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排序方式: 共有249条查询结果,搜索用时 31 毫秒
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BACKGROUND: Estrogen receptors alpha and beta (ERalpha and ERbeta) differentially activate genes with AP-1 elements. ERalpha activates AP-1 targets via activation functions with estrogens (the AF-dependent pathway), whereas ERbeta, and a short version of ERalpha (ERalpha DBD-LBD) activate only with anti-estrogens (AF-independent pathway). The DNA binding domain (DBD) plays an important role in both pathways, even though neither pathway requires ERE recognition. RESULTS: Mutations of a highly conserved DBD lysine (ERalpha.K206A/G), lead to super-activation of AP-1 through activation function dependent pathways, up to 200 fold. This super-activity can be elicited either through ER AFs 1 or 2, or that of a heterologous activation function (VP16). The homologous substitution in ERbeta, K170A, or in ERalpha DBD-LBD leads to estrogen-dependent AP-1 activation and loss of the usually potent anti-estrogen effects. Each of numerous K206 substitutions in ERalpha, except K206R, eliminates anti-estrogen activation and this loss correlates perfectly with a loss of ability to titrate a repressive function from the RU486 bound progesterone receptor. CONCLUSION: We conclude that ER DBDs contain a complex regulatory function that influences ligand activation profiles at AP-1. This function, which requires the integrity of the conserved lysine, both allows for activation at AP-1 with anti-estrogens (with ERbeta and ERalpha DBD-LBD), and prevents ERalpha from becoming superactive at AP-1 with estrogens. We discuss the possibility that a repressor interaction with the DBD both mediates the AF-independent pathway and dampens the AF dependent pathway. Mutations in the conserved lysine might, by this model, disrupt the binding or function of the repressor. 相似文献
74.
Collectins and ficolins: sugar pattern recognition molecules of the mammalian innate immune system 总被引:16,自引:0,他引:16
Collectins and ficolins represent two important groups of pattern recognition molecules, which bind to oligosaccharide structures on the surface of microorganisms, leading to the killing of bound microbes through complement activation and phagocytosis. Collectins and ficolins bear no significant sequence homology except for the presence of collagen-like sequences over the N-terminal halves of the polypeptides that enable the assembly of these molecules into oligomeric structures. Collectins and ficolins both contain lectin activities within the C-terminal halves of their polypeptides, the C-type carbohydrate recognition domain (CRDs) and fibrinogen beta/gamma (homology) (FBG) domain, respectively. These domains form trimeric clusters at the ends of the collagen triple helices emanating from a central hub, where the N-terminal ends of the polypeptides merge. The collectins and ficolins seem to have evolved to recognize the surface sugar codes of microbes and their binding, to these arrays of cell surface carbohydrate molecules, targets the microbe for subsequent clearance by phagocytic cells. 相似文献
75.
Calcium coordination studies of the metastatic Mts1 protein 总被引:3,自引:0,他引:3
Mts1, also known as S100A4, is an 11 kDa calcium-binding protein strongly linked to metastasis. As a member of the S100 protein family, Mts1 is predicted to contain four alpha-helices and two calcium-binding loops, the second of which forms a canonical EF hand, while the first is a pseudo-EF hand, using two extra residues and principally backbone carbonyls rather than side chain oxygens to coordinate calcium. Here we follow chemical shift changes which occur in Mts1 upon titration of calcium. The results are consistent with calcium coordination by the EF hands described above. Filling of the first (pseudo) EF hand occurs at a lower calcium concentration than does filling of the second (canonical) EF hand. Concurrent with filling of site I, resonances from much of helix 4 vanish while the chemical shifts of a possibly nascent helical segment immediately C-terminal to helix 4 increase in helical character. Other smaller changes are seen, including a change in the linker joining helix 2 and helix 3. Since binding of effector molecules to S100 proteins has been shown to involve the C-terminus and linker regions, these calcium-induced changes have implications for the role of Mts1 in metastasis. 相似文献
76.
Cathleen Haase-Kohn Susann Wolf Nadine Herwig Birgit Mosch Jens Pietzsch 《Biochemical and biophysical research communications》2014
S100A4, synthesized and secreted from both tumor and stroma cells, modulates an aggressive tumor phenotype in various cancers by intracellular and extracellular interactions which are not completely understood. Because of the high content of tumor-associated macrophages in melanoma, here, a syngeneic model (coculture of mouse B16-F10 melanoma cells (Mel) and RAW264.7 macrophages (M?); administration (i.v.) of Mel and M?/Mel in NMRI nu/nu mice) was used to investigate synthesis and secretion of (a) S100A4, (b) S100A4-mediated signaling and activation of NFκB, and (c) S100A4-mediated modulation of Mel invasiveness in vitro (transwell assay, transwell matrigel assay) and in vivo (metastatic lung colonization), respectively. In this model substantial S100A4 synthesis and secretion is demonstrated in M?. Macrophage-derived S100A4 promotes Mel invasiveness in a paracrine manner in vitro, which is further substantiated in control experiments using recombinant human S100A4 and Mel stably transfected with mouse S100A4. Moreover, the participation of S100A4-mediated signaling, e.g., via the receptor for advanced glycation endproducts (RAGE), resulting in activation of NFκB was demonstrated in all experimental settings. Finally, we demonstrated that interaction of macrophage-derived S100A4 with Mel results in increased metastatic lung colonization in vivo. 相似文献
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78.
Riggers Catharina Poeplau Christopher Don Axel Frühauf Cathleen Dechow René 《Plant and Soil》2021,460(1-2):417-433
Plant and Soil - Increasing soil organic carbon (SOC) stocks is discussed as negative emission technology with the potential to remove relevant amounts of carbon from the atmosphere. At the same... 相似文献
79.
The sympathetic nervous system regulates cardiac output by activating adrenergic receptors (ARs) in cardiac myocytes. The predominant cardiac ARs, β(1)- and β(2)AR, are structurally similar but mediate distinct signaling responses. Scaffold protein-mediated compartmentalization of ARs into discrete, multiprotein complexes has been proposed to dictate differential signaling responses. To test the hypothesis that βARs integrate into complexes in live cells, we measured receptor diffusion and interactions by single-particle tracking. Unstimulated β(1)- and β(2)AR were highly confined in the membrane of H9c2 cardiomyocyte-like cells, indicating that receptors are tethered and presumably integrated into protein complexes. Selective disruption of interactions with postsynaptic density protein 95/disks large/zonula occludens-1 (PDZ)-domain proteins and A-kinase anchoring proteins (AKAPs) increased receptor diffusion, indicating that these scaffold proteins participate in receptor confinement. In contrast, modulation of interactions between the putative scaffold caveolae and β(2)AR did not alter receptor dynamics, suggesting that these membrane domains are not involved in β(2)AR confinement. For both β(1)- and β(2)AR, the receptor carboxy-terminus was uniquely responsible for scaffold interactions. Our data formally demonstrate that distinct and stable protein complexes containing β(1)- or β(2)AR are formed in the plasma membrane of cardiomyocyte-like cells and that selective PDZ and AKAP interactions are responsible for the integration of receptors into complexes. 相似文献
80.
Peter M. J. Brown Cathleen E. Thomas Eric Lombaert Daniel L. Jeffries Arnaud Estoup Lori-Jayne Lawson Handley 《BioControl》2011,56(4):623-641
Released as a biological control agent of aphids and coccids, Harmonia axyridis (Coleoptera: Coccinellidae) has spread from Asia to four additional continents. Since 1988 H. axyridis has established in at least 38 countries in its introduced range: three countries in North America, six in South America,
26 in Europe and three in Africa. In different continents the species has spread at rates estimated between 100 and 500 km year−1. Here, the global spread of H. axyridis is thoroughly reviewed. Mechanisms of short- and long-distance dispersal in coccinellids are discussed, as are the reasons
for them, with particular emphasis on H. axyridis. Dispersal via anthropogenic means has been particularly important in the case of H. axyridis. Preliminary studies investigating the invasion routes of H. axyridis using genetic analyses (involving both microsatellite and mitochondrial DNA) are outlined. 相似文献