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71.
72.
The productive activation of CD4(+) T lymphocytes, leading to proliferation and cytokine secretion, requires precise temporal regulation of intracellular cyclic AMP concentrations. The major effector molecule activated by cyclic AMP in mammalian cells is the cyclic AMP-dependent protein kinase A (PKA). The type I PKA isozyme mediates the inhibitory effects of cyclic AMP on T-cell activation. Using laser scanning confocal microscopy, we demonstrated that the regulation of PKA type I activity involves spatial redistribution of PKA type I molecules following T-cell receptor (TCR) stimulation. In resting T cells, PKA type I was located in membrane proximal regions and distributed equally across the cell. Shortly after antigen engagement, T cells and antigen-presenting cells formed an area of intense contact, known as the immunological synapse. TCR concentrated at the synapse, whereas PKA type I molecules redistributed to the opposite cell pole within 10 min after T-cell stimulation. Type I PKA redistribution was solely dependent on TCR signalling, because we observed the same temporal and spatial distribution after antibody-mediated cross-linking of the TCR-associated CD3 complex. Segregation of TCR and PKA type I molecules was maintained for at least 20 min. Thirty minutes after stimulation, PKA type I partially colocalized with the TCR. After 60 min, PKA type I distribution again approached the resting state. Considering that initial TCR signals lead to increases in intracellular cyclic AMP, PKA type I molecules may be targeted towards localized cyclic AMP accumulations or transported away from these areas, depending on the requirements of the cellular response. 相似文献
73.
Putney JW 《Pflügers Archiv : European journal of physiology》2005,451(1):29-34
TRPC (canonical transient receptor potential) channels are vertebrate homologs of the Drosophila photoreceptor channel, TRP. Considerable research has been brought to bear on the seven members of this family, especially with regard to their possible role in calcium entry. Unfortunately, the current literature presents a confusing picture, with different laboratories producing widely differing results and interpretations. It appears that ectopically expressed TRPC channels can be activated by phospholipase C products (generally, diacylglycerols), by stimulation of trafficking to the plasma membrane, or by depletion of intracellular Ca2+ stores. Here, I discuss the possibility that these diverse experimental findings arise because TRPC channels can, under both experimental as well as physiological conditions, be activated in three distinct ways, possibly depending on their subunit composition and/or signaling complex environment. The TRPCs may be unique among ion-channel subunit families in being able to participate in the assembly and function of multiple types of physiologically important ion channels. 相似文献
74.
目的:在钙化大鼠主动脉血管平滑肌细胞上观察血管紧张素-(1-7)[Angiotensin-(1-7)]对钙化的影响及其信号通道。方法:用β-磷酸甘油制备钙化的大鼠血管平滑肌细胞,再以血管紧张素-(1-7)、血管紧张素Ⅱ、血管紧张素Ⅱ 血管紧张素-(1-7)、选择性蛋白激酶A(PKA)或蛋白激酶C(PKC)抑制剂等干预,通过Von Kossa染色及检测钙含量、碱性磷酸酶活性、骨钙素浓度和Cbfa1 mRNA表达来探讨血管紧张素Ⅱ对钙化的影响及其信号通道。结果:血管紧张素-(1-7)抑制钙化大鼠血管平滑肌细胞的钙含量、碱性磷酸酶活性(P>0.05)、骨钙素浓度和Cbfa1 mRNA表达(P<0.05),也抑制血管紧张素Ⅱ对血管平滑肌细胞的钙含量、碱性磷酸酶活性、骨钙素浓度和Cbfa1 mRNA表达的促进作用(P<0.05);血管紧张素-(1-7)提高血管平滑肌细胞内cAMP浓度(P<0.05),PKA抑制剂可阻断血管紧张素-(1-7)对钙化血管平滑肌细胞的钙含量、碱性磷酸酶活性、骨钙素浓度和Cbfa1 mRNA表达的抑制作用(P<0.05)。结论:血管紧张素-(1-7)可抑制β-磷酸甘油诱导的血管平滑肌细胞钙化,并拮抗血管紧张素Ⅱ促进的血管平滑肌细胞钙化;这些效应与cAMP-PKA-Cbfa1信号途径有关。 相似文献
75.
Straube E Knöfel B Schneider T Schubert S Wetzker R 《International journal of medical microbiology : IJMM》2000,290(1):65-73
Adhesion to and internalization into host cells is an essential step in the pathogenesis of various bacterial infections. Here we investigated the effects of growth factors on the internalization of Escherichia coli O18 strains isolated from patients with urinary tract infection (UTI) by human epithelial cells. A dramatic increase in the uptake of Escherichia coli was observed after treatment of epithelial cells with epidermal growth factor (EGF) and to a lower extent with insulin. EGF-dependent internalization can be suppressed by tyrosine kinase inhibitors suggesting an involvement of the receptor tyrosine kinases in the regulation of the endocytotic process. Inhibitors of phospholipase A2, lipoxygenase, and cyclooxygenase significantly decreased internalization of bacteria induced by EGF. Finally, the specific inhibitor of PI 3-kinases Wortmannin was shown to suppress completely the EGF-independent internalization. The data of this analysis indicate the involvement of several signaling paths in bacterial internalization of uropathogenic Escherichia coli O18 strains and contribute to the comprehension of the pathogenesis of recurrent UTI. 相似文献
76.
A 1.0-kb DNA fragment, corresponding to an internal region of the Neurospora crassa glucoamylase gene, gla-1, was generated from genomic DNA by the polymerase chain reaction, using oligonucleotide primers which had been deduced from the known N-terminal amino-acid sequence or from consensus regions within the aligned amino-acid sequences of other fungal glucoamylases. The fragment was used to screen an N. crassa genomic DNA library. One clone contained the gene together with flanking regions and its sequence was determined. The gene was found to code for a preproprotein of 626 amino acids, 35 of which constitute a signal and propeptide region. The protein and the gene are compared with corresponding sequences in other fungi. 相似文献
77.
Zhiyong Wang Zhongcheng Zheng Lanyin Sun Xinyuan Liu 《European journal of immunology》1995,25(5):1212-1216
Human interleukin-2 (IL-2) α helix B is more conserved than the whole molecule, but has been less studied than other α helices of IL-2. Using site-directed mutagenesis, several IL-2 mutants in this helix were obtained. We found that the IL-2 mutant containing Leu at position 62 (Leu62-IL-2) loses its ability to bind IL-2 receptor subunit α (IL-2Rα), but retains binding affinity to IL-2R subunit βγ as well as some bioactivity; nevertheless, another substitution at the same residue, Arg62 IL-2, loses its binding ability to both IL-2Rα and IL-2Rβγ, and can no longer stimulate IL-2-dependent cell growth, showing that Glu62 not only takes part in IL-2Rα binding, but can also affect IL-2 binding to IL-2Rβγ. In this regard, Glu62 may be a key site in the IL-2/IL-2Rα interaction, and can facilitate IL-2R ternary-complex formation, leading to IL-2Rα-mediated, IL-2-stimulated signal transduction. 相似文献
78.
Interleukin-2 (IL-2), secreted principally by activated helper T-cells, plays a pivotal role in the generation and regulation
of the immune response. The various biologic functions of IL-2 have been the focus of intensive study over the years and have
been well worked out. By contrast, an understanding of the intracellular signals coupled to the IL-2 receptor and responsible
for mediating IL-2 effects in T-cells is far less developed, and the role that protein kinase C (PKC) may play in the various
cellular responses to IL-2 receptor activation is unclear. In this article we will discuss IL-2, its receptors, and IL-2 signal
transduction in relation to the physiological roles PKC activation may play in IL-2-mediated activation of T-cells and other
hematopoietic cells. 相似文献
79.
Reduced protein tyrosine phosphatase (PTPase) activity of CD45 on peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE) 总被引:3,自引:0,他引:3 下载免费PDF全文
To disclose the mechanism of aberrant function of peripheral blood lymphocytes (PBL) in SLE, we focused on the catalytic function of CD45, and determined the CD45 PTPase activity in SLE patients. The sample population consisted of 32 SLE patients with different disease activity. PTPase activity of cell lysates immunoprecipitated by anti-CD45 MoAb was assayed against phosphotyrosine analogue PNPP, followed by measuring the release of para-nitro phenol at 410 nm. CD45 PTPase activity of PBL was significantly decreased in SLE patients, compared with that of normal controls and patients with systemic sclerosis (964 ± 265, 1202 ± 172, 1210 ± 125, respectively; SLE versus normal, P < 0.05). It was correlated with SLE Disease Activity Index (SLEDAI) score (r = 0.597, P = 0.0006), but not with the dose of prednisolone (r = 0.214, P = 0.2657), indicating that CD45 PTPase activity became reduced when the disease was active, but it was not affected by prednisolone. Moreover, it was not corrected by in vitro culture with or without stimulation. The expression of CD45 on PBL was comparable between normal and SLE, raising a possibility that it may be due to aberrant regulation of catalytic function of CD45 in SLE. Given the evidence that tyrosine phosphorylation of cellular proteins by tyrosine kinases and phosphatases is one of the key biochemical events in the signal transduction pathway, the decreased CD45 PTPase activity in SLE may account for the defective signal transduction via TCR/CD3, leading to dysregulated effector function of the lymphocytes. 相似文献
80.
EB病毒LMP1在鼻咽癌细胞系中通过NF-κB、AP-1促进IL-8分泌 总被引:1,自引:0,他引:1
目的:探讨EB病毒LMP1分子致瘤机制,在已证实鼻咽癌细胞系中LMP1有效激活NF-κB 或AP-1的基础上,对LMP1是否通过NF-κB 或AP-1促进IL-8分泌进行探讨。方法:以稳定表达LMP1及其3种突变体,空白载体的鼻咽癌细胞系[HNE2-LMP1,NHE2-MLP1(1-185),HNE2-LMP1(1-231),HNE2-LMP1Δ187-351和HNF3-pSG5]及antisense-LMP1处理的HNF2-LMP1鼻咽癌的细胞系为材料,将IL-8报道质粒瞬时导入这些细胞系中,通过测定luciferase值以反映LMP1是否促进IL-8转录;将mut AP-1/IL-8-luc或IκB α(S32A/S36A)表达质粒导入HNE2-LMP1细胞系中,比较其IL-8报道活性,以确定LMP1是否通过AP-1或NF-κB 诱导IL-8转录;利用ELISA方法测定HNE2-LMP1,HNE2-pSG5,anti-sese-LMP1处理的HNE2-LMP1鼻咽癌细胞系中的IL-8浓度,进一步从蛋白水平上确定LMP1是否促进IL-8分泌。结果:与HNE2-pSG5相比,在HNE2-LMP1,HNE2-LMP1Δ187-351和HNE2-LMP1(1-231)细胞系中IL-8报道活性分别升高了原来水平的11.5,8.6和3.4倍,而HNE2-LMP1(1-185)对IL-8报道活性不影响。在HNE2-LMP1细胞系中IL-8蛋白水平提高了17.4倍,而antisense-LMP1则使HNE2-LMP1细胞的IL-8报道活性及蛋白水平分别下降到原来水平的18.3%和9.2%,导入mutAP-1/IL-8-luc或IκBα(S32A/S36A)的HNE2-LMP1细胞中IL-8报道活性分别下降到原有水平39%和26%,结论:鼻咽癌细胞系中LMP1可能通过NF-κAP-1促进IL-8表达。 相似文献