排序方式: 共有35条查询结果,搜索用时 15 毫秒
31.
Zou P Pinotsis N Lange S Song YH Popov A Mavridis I Mayans OM Gautel M Wilmanns M 《Nature》2006,439(7073):229-233
The Z-disk of striated and cardiac muscle sarcomeres is one of the most densely packed cellular structures in eukaryotic cells. It provides the architectural framework for assembling and anchoring the largest known muscle filament systems by an extensive network of protein-protein interactions, requiring an extraordinary level of mechanical stability. Here we show, using X-ray crystallography, how the amino terminus of the longest filament component, the giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich complex by the Z-disk ligand telethonin. The pseudosymmetric structure of telethonin mediates a unique palindromic arrangement of two titin filaments, a type of molecular assembly previously found only in protein-DNA complexes. We have confirmed its unique architecture in vivo by protein complementation assays, and in vitro by experiments using fluorescence resonance energy transfer. The model proposed may provide a molecular paradigm of how major sarcomeric filaments are crosslinked, anchored and aligned within complex cytoskeletal networks. 相似文献
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Glucagon-like peptide-1(1-37) inhibits chemokine-induced migration of human CD4-positive lymphocytes
Nikolaus Marx Mathias Burgmaier Philipp Heinz Mirjam Ostertag Angelina Hausauer Helga Bach Renate Durst Vinzenz Hombach Daniel Walcher 《Cellular and molecular life sciences : CMLS》2010,67(20):3549-3555
The present study examined the effect of GLP-1(1-37) on chemokine-induced CD4-positive lymphocyte migration as an early and
critical step in atherogenesis. Pretreatment with GLP-1(1-37) reduced the SDF-induced migration of isolated human CD4-positive
lymphocytes in a concentration-dependent manner. Similar effects were seen when RANTES was used as a chemokine. GLP-1(1-37)’s
effect on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity.
Downstream, GLP-1(1-37) inhibited SDF-induced phosphorylation of MLC and cofilin and limited f-actin formation as well as
ICAM3 translocation. Furthermore, exendin-4 inhibited SDF-induced migration of CD4-positive lymphocytes similarly to GLP-1(1-37),
and transfection of these cells with GLP-1 receptor siRNA abolished GLP-1(1-37)’s action on chemokine-induced ICAM3 translocation,
suggesting an effect mediated via the GLP-1 receptor. Thus, GLP-1(1-37) inhibits chemokine-induced CD4-positive lymphocyte
migration by inhibition of the PI3-kinase pathway and via the GLP-1 receptor. This effect provides a potential novel mechanism
for how GLP-1(1-37) may modulate vascular disease. 相似文献
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Ueda H Howson JM Esposito L Heward J Snook H Chamberlain G Rainbow DB Hunter KM Smith AN Di Genova G Herr MH Dahlman I Payne F Smyth D Lowe C Twells RC Howlett S Healy B Nutland S Rance HE Everett V Smink LJ Lam AC Cordell HJ Walker NM Bordin C Hulme J Motzo C Cucca F Hess JF Metzker ML Rogers J Gregory S Allahabadia A Nithiyananthan R Tuomilehto-Wolf E Tuomilehto J Bingley P Gillespie KM Undlien DE Rønningen KS Guja C Ionescu-Tîrgovişte C Savage DA Maxwell AP Carson DJ Patterson CC Franklyn JA 《Nature》2003,423(6939):506-511
Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the immune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism and type 1 diabetes. In humans, disease susceptibility was mapped to a non-coding 6.1 kb 3' region of CTLA4, the common allelic variation of which was correlated with lower messenger RNA levels of the soluble alternative splice form of CTLA4. In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain. Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders, as exemplified by our discovery of inherited, quantitative alterations of CTLA4 contributing to autoimmune tissue destruction. 相似文献
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