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排序方式: 共有1346条查询结果,搜索用时 15 毫秒
1.
Pasupathi Sundaramoorthy Jae Jun Sim Yeong-Su Jang Siddhartha Kumar Mishra Keun-Yeong Jeong Poonam Mander Oh Byung Chul Won-Sik Shim Seung Hyun Oh Ky-Youb Nam Hwan Mook Kim 《PloS one》2015,10(1)
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer. 相似文献
2.
Levels of polyamines, glutathione and glutathione-spermidine conjugates during growth of the insect trypanosomatid Crithidia fasciculata 总被引:4,自引:0,他引:4
Levels of the polyamines spermidine and putrescine and the major intracellular thiols glutathione (GSH), glutathionylspermidine (GSH-SPD) and dihydrotrypanothione [bis-(glutathionyl)spermidine); T[SH]2] were measured by high performance liquid chromatography throughout the growth cycle of the insect trypanosomatid Crithidia fasciculata. The amount of total spermidine, putrescine and glutathione (free and conjugated to spermidine) was found to be elevated during growth. Of the total spermidine, 30 to 50% was found conjugated to glutathione during the exponential growth phase, increasing to 60 to 70% at stationary phase. T[SH]2 was the principal intracellular thiol during exponential growth (12.1 to 17.4 nmol per 10(8) cells), whereas GSH-SPD was the major thiol in stationary phase (26.2 nmol per 10(8) cells). GSH levels changed little during the growth cycle and represented a constant proportion (10 to 12%) of the total intracellular glutathione. On dilution of stationary phase cells into fresh medium, a rapid decrease in GSH-SPD levels was observed to be associated with synthesis of T[SH]2. This process reached 90% completion by 15 min, with steady state achieved by 120 min. As the total spermidine and glutathione pools did not increase during this interval, it could be calculated that this rapid redistribution of metabolites resulted in the release of 13 nmol per 10(8) cells unconjugated spermidine without de novo synthesis. This mechanism for rapidly elevating the intracellular concentration of free spermidine may be advantageous to this organism in rapidly adapting to favourable growth conditions. 相似文献
3.
4.
The ATP-binding-cassette transmembrane transporters (ABC transporters)
known from vertebrates belong to four major subfamilies: (1) the P-
glycoproteins (Pgp); (2) the cystic fibrosis transmembrane conductance
regulators (CFTR); (3) the Tap proteins encoded with the major
histocompatibility complex of mammals; and (4) the peroxisomal membrane
proteins. Both Pgp and CFTR have a structure suggesting a past internal
gene duplication; a phylogenetic analysis indicated that these duplications
occurred independently, while an independent tandem gene duplication
occurred in the case of the Tap family. Both the Pgp and Tap proteins show
evidence of relationship to bacterial ABC transporters lacking internal
duplication, and both are significantly more closely related to the HlyB
and MsbA families of transporters from purple bacteria than they are to ABC
transporters from nonpurple bacteria. The simplest hypothesis to explain
this observation is that eukaryotic Pgp and Tap genes are descended from a
mitochondrial gene or genes that were subsequently translocated to the
nuclear genome. The Pgp genes of eukaryotes are characterized by a
remarkable degree of convergent evolution between the ATP-binding cassettes
of their N- terminal and C-terminal halves, whereas no such convergence is
seen between the two halves of CFTR genes or between the duplicated Tap
genes. Exon 13 of the CFTR gene, which encodes a putative regulatory domain
not found in other ABC transporters apart from CFTR, showed high levels of
both synonymous and nonsynonymous difference in comparisons among different
mammalian species, suggesting that this region is a mutational hot spot.
相似文献
5.
6.
Sua Jeong Ji Seon Shim Seok Kyo Sin Kang-Sik Park Jung-Ha Lee 《Journal of cellular physiology》2023,238(1):210-226
Cav3.1 T-type Ca2+ channels play pivotal roles in neuronal low-threshold spikes, visceral pain, and pacemaker activity. Phosphorylation has been reported to potently regulate the activity and gating properties of Cav3.1 channels. However, systematic identification of phosphorylation sites (phosphosites) in Cav3.1 channel has been poorly investigated. In this work, we analyzed rat Cav3.1 protein expressed in HEK-293 cells by mass spectrometry, identified 30 phosphosites located at the cytoplasmic regions, and illustrated them as a Cav3.1 phosphorylation map which includes the reported mouse Cav3.1 phosphosites. Site-directed mutagenesis of the phosphosites to Ala residues and functional analysis of the phospho-silent Cav3.1 mutants expressed in Xenopus oocytes showed that the phospho-silent mutation of the N-terminal Ser18 reduced its current amplitude with accelerated current kinetics and negatively shifted channel availability. Remarkably, the phospho-silent mutations of the C-terminal Ser residues (Ser1924, Ser2001, Ser2163, Ser2166, or Ser2189) greatly reduced their current amplitude without altering the voltage-dependent gating properties. In contrast, the phosphomimetic Asp mutations of Cav3.1 on the N- and C-terminal Ser residues reversed the effects of the phospho-silent mutations. Collectively, these findings demonstrate that the multiple phosphosites of Cav3.1 at the N- and C-terminal regions play crucial roles in the regulation of the channel activity and voltage-dependent gating properties. 相似文献
7.
X Xiao G Hintermann AL Demanin J Piret 《Journal of industrial microbiology & biotechnology》1996,16(4):261-262
Streptomyces glaucescens is shown to possess -lactamase activity which is inhibitable by clavulanate. This is important in regard to its use as a cloning host for enzymes of \-lactam biosynthesis. 相似文献
8.
9.
Zehua Zhou Yabing Duan Jie Zhang Fei Lu Yuanye Zhu Won Bo Shim Mingguo Zhou 《Molecular Plant Pathology》2021,22(2):163-174
In Fusarium graminearum, a trichothecene biosynthetic complex known as the toxisome forms ovoid and spherical structures in the remodelled endoplasmic reticulum (ER) under mycotoxin-inducing conditions. Previous studies also demonstrated that disruption of actin and tubulin results in a significant decrease in deoxynivalenol (DON) biosynthesis in F. graminearum. However, the functional association between the toxisome and microtubule components has not been clearly defined. In this study we tested the hypothesis that the microtubule network provides key support for toxisome assembly and thus facilitates DON biosynthesis. Through fluorescent live cell imaging, knockout mutant generation, and protein–protein interaction assays, we determined that two of the four F. graminearum tubulins, α1 and β2 tubulins, are indispensable for DON production. We also showed that these two tubulins are directly associated. When the α1–β2 tubulin heterodimer is disrupted, the metabolic activity of the toxisome is significantly suppressed, which leads to significant DON biosynthesis impairment. Similar phenotypic outcomes were shown when F. graminearum wild type was treated with carbendazim, a fungicide that binds to microtubules and disrupts spindle formation. Based on our results, we propose a model where α1–β2 tubulin heterodimer serves as the scaffold for functional toxisome assembly in F. graminearum. 相似文献
10.
As part of the development of carbon-coated prosthetic devices, the adhesion of thin carbon films to metallic substrates has been studied. The bond strength of carbon films about 5000 A thick on Ti-6A1-4V and stainless steel was measured in a pull test and found to be greater than 4700 psi. Auger electron spectroscopy showed a reactive film/substrate interface. The ultimate bond strength was found to be dependent on the substrate and the deposition parameters. 相似文献