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51.
Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4 总被引:25,自引:0,他引:25
Yamamoto M Sato S Hemmi H Sanjo H Uematsu S Kaisho T Hoshino K Takeuchi O Kobayashi M Fujita T Takeda K Akira S 《Nature》2002,420(6913):324-329
Signal transduction through Toll-like receptors (TLRs) originates from their intracellular Toll/interleukin-1 receptor (TIR) domain, which binds to MyD88, a common adaptor protein containing a TIR domain. Although cytokine production is completely abolished in MyD88-deficient mice, some responses to lipopolysaccharide (LPS), including the induction of interferon-inducible genes and the maturation of dendritic cells, are still observed. Another adaptor, TIRAP (also known as Mal), has been cloned as a molecule that specifically associates with TLR4 and thus may be responsible for the MyD88-independent response. Here we report that LPS-induced splenocyte proliferation and cytokine production are abolished in mice lacking TIRAP. As in MyD88-deficient mice, LPS activation of the nuclear factor NF-kappaB and mitogen-activated protein kinases is induced with delayed kinetics in TIRAP-deficient mice. Expression of interferon-inducible genes and the maturation of dendritic cells is observed in these mice; they also show defective response to TLR2 ligands, but not to stimuli that activate TLR3, TLR7 or TLR9. In contrast to previous suggestions, our results show that TIRAP is not specific to TLR4 signalling and does not participate in the MyD88-independent pathway. Instead, TIRAP has a crucial role in the MyD88-dependent signalling pathway shared by TLR2 and TLR4. 相似文献
52.
Arabidopsis boron transporter for xylem loading 总被引:21,自引:0,他引:21
Takano J Noguchi K Yasumori M Kobayashi M Gajdos Z Miwa K Hayashi H Yoneyama T Fujiwara T 《Nature》2002,420(6913):337-340
Boron deficiency hampers the productivity of 132 crops in more than 80 countries. Boron is essential in higher plants primarily for maintaining the integrity of cell walls and is also beneficial and might be essential in animals and in yeast. Understanding the molecular mechanism(s) of boron transport is crucial for alleviating boron deficiency. Here we describe the molecular identification of boron transporters in biological systems. The Arabidopsis thaliana mutant bor1-1 is sensitive to boron deficiency. Uptake studies indicated that xylem loading is the key step for boron accumulation in shoots with a low external boron supply and that the bor1-1 mutant is defective in this process. Positional cloning identified BOR1 as a membrane protein with homology to bicarbonate transporters in animals. Moreover, a fusion protein of BOR1 and green fluorescent protein (GFP) localized to the plasma membrane in transformed cells. The promoter of BOR1 drove GFP expression in root pericycle cells. When expressed in yeast, BOR1 decreased boron concentrations in cells. We show here that BOR1 is an efflux-type boron transporter for xylem loading and is essential for protecting shoots from boron deficiency. 相似文献
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54.
RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems 总被引:28,自引:0,他引:28
Kobayashi K Inohara N Hernandez LD Galán JE Núñez G Janeway CA Medzhitov R Flavell RA 《Nature》2002,416(6877):194-199
The immune system consists of two evolutionarily different but closely related responses, innate immunity and adaptive immunity. Each of these responses has characteristic receptors-Toll-like receptors (TLRs) for innate immunity and antigen-specific receptors for adaptive immunity. Here we show that the caspase recruitment domain (CARD)-containing serine/threonine kinase Rip2 (also known as RICK, CARDIAK, CCK and Ripk2) transduces signals from receptors of both immune responses. Rip2 was recruited to TLR2 signalling complexes after ligand stimulation. Moreover, cytokine production in Rip2-deficient cells was reduced on stimulation of TLRs with lipopolysaccharide, peptidoglycan and double-stranded RNA, but not with bacterial DNA, indicating that Rip2 is downstream of TLR2/3/4 but not TLR9. Rip2-deficient cells were also hyporesponsive to signalling through interleukin (IL)-1 and IL-18 receptors, and deficient for signalling through Nod proteins-molecules also implicated in the innate immune response. Furthermore, Rip2-deficient T cells showed severely reduced NF-kappaB activation, IL-2 production and proliferation on T-cell-receptor (TCR) engagement, and impaired differentiation to T-helper subtype 1 (TH1) cells, indicating that Rip2 is required for optimal TCR signalling and T-cell differentiation. Rip2 is therefore a signal transducer and integrator of signals for both the innate and adaptive immune systems. 相似文献
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56.
Cerebral capillary endothelium forms a barrier limiting and controlling the movement of ions and solutes between blood and brain. Recent anatomical, physiological and biochemical studies have suggested the possibility that capillary function may be directly controlled by neuronal structures. Alterations in neuronal systems involved in the regulation of microcirculation may account for microvascular dysfunctions which occur in different pathologic conditions. 相似文献
57.
J. Kobayashi M. Ishibashi H. Nakamura Y. Hirata T. Yamasu T. Sasaki Y. Ohizumi 《Cellular and molecular life sciences : CMLS》1988,44(9):800-802
Summary A novel sphingosine derivative, symbioramide, has been isolated from the laboratory-cultured dinoflagellateSymbiodinium sp. as a sarcoplasmic reticulum (SR) Ca2+-ATPase activator, and its structure elucidated to be1 on the basis of spectral and chemical means.Acknowledgments. We thank Ms M. Hamashima and Ms A. Muroyama for their technical assistance. 相似文献
58.
A 14-membered ring diterpenoid named cembrane, possessing Ca-antagonistic action on the isolated rabbit aorta, has been isolated from a soft coral of the genus Sarcophyton, and its structure established by X-ray and spectroscopic data. 相似文献
59.
Isolation and amino acid compositions of geographutoxin I and II from the marine snail Conus geographus 总被引:3,自引:0,他引:3
The peptide toxins having inhibitory effects on the contractile response of the mouse diaphragm to direct stimulation, geographutoxin I and II, have been isolated from Conus geographus, and their amino acid compositions have been determined. 相似文献
60.
Lipid peroxides in rabbit erythrocytes and plasma were determined while anemia was induced by daily bleeding. They increased as reticulocytes increased and returned to normal with the morphological transformation to mature cells. 相似文献