排序方式: 共有100条查询结果,搜索用时 15 毫秒
91.
92.
Cinar B Fang PK Lutchman M Di Vizio D Adam RM Pavlova N Rubin MA Yelick PC Freeman MR 《The EMBO journal》2007,26(21):4523-4534
Akt kinases mediate cell growth and survival. Here, we report that a pro-apoptotic kinase, Mst1/STK4, is a physiological Akt1 interaction partner. Mst1 was identified as a component of an Akt1 multiprotein complex isolated from lipid raft-enriched fractions of LNCaP human prostate cancer cells. Endogenous Mst1, along with its paralog, Mst2, acted as inhibitors of endogenous Akt1. Surprisingly, mature Mst1 as well as both of its caspase cleavage products, which localize to distinct subcellular compartments and are not structurally homologous, complexed with and inhibited Akt1. cRNAs encoding full-length Mst1, and N- and C-terminal caspase Mst1 cleavage products, reverted an early lethal phenotype in zebrafish development induced by expression of membrane-targeted Akt1. Mst1 and Akt1 localized to identical subcellular sites in human prostate tumors. Mst1 levels declined with progression from clinically localized to hormone refractory disease, coinciding with an increase in Akt activation with transition from hormone naïve to hormone-resistant metastases. These results position Mst1/2 within a novel branch of the phosphoinositide 3-kinase/Akt pathway and suggest an important role in cancer progression. 相似文献
93.
Novel forms of Pin-II type proteinase inhibitor (PIs) cDNAs (CanPIs) having three or four inhibitory repeat domains (IRD) were isolated from the developing green fruits of Capsicum annuum. Deduced amino acid (aa) sequences of the CanPIs showed up to 15% sequence divergence among each other or reported inhibitors (CanPI-1AF039398, CanPI-2AF221097). Amino acid sequence analysis of these CanPIs revealed that three IRD PIs have trypsin inhibitory sites, while four IRD CanPIs have both trypsin and chymotrypsin inhibitory sites. Four CanPIs, two having three IRD (CanPI-3AY986465 and CanPI-5DQ005912) and two having four IRD (CanPI-7DQ005913 and CanPI-9DQ005915), were cloned in Pichia pastoris to express recombinant CanPIs. Recombinant CanPIs inhibited 90% of bovine trypsin (TI), while chymotrypsin inhibition (CI) varied with the number of chymotrypsin inhibitory sites in the CanPIs. Recombinant inhibitors inhibited over 70% of the gut proteinase activity of Helicoverpa armigera. H. armigera larvae fed on recombinant CanPIs individually incorporated into artificial diet, showed 35% mortality; in addition, weight gain in H. armigera larvae and pupae was severely reduced compared to controls. Of the four CanPIs, CanPI-7, which has two sites for TI and CI, was the only one to have a consistently antagonistic effect on H. armigera growth and development. We conclude that among the four recombinant PIs tested, CanPIs containing diverse IRDs are best suited for developing insect-resistant transgenic plants. 相似文献
94.
Yadav Pavan Kumar Gupta Shishir Kumar Kumar Saroj Ghosh Mayukh Yadav Brijesh Singh Kumar Dinesh Kumar Ajay Saini Mohini Kataria Meena 《Molecular and cellular biochemistry》2021,476(1):311-320
Molecular and Cellular Biochemistry - Matrix Metalloproteinases (MMPs)-induced altered proteolysis of extracellular matrix proteins and basement membrane holds the key for tumor progression and... 相似文献
95.
To study the underlying mechanism of gonadal growth during the attainment of puberty and to test a coincidence model, 7 experimental
groups of 2-week-old male mice, Mus musculus, were administered the serotonin precursor, 5-hydroxytryptophan, followed by the dopamine precursor, l-dihydroxyphenylalanine at hourly intervals of 6, 7, 8, 9, 10, 11 and 12 h (5 mg/100 g body weight per day for 13 days). At
11 days post-treatment, a suppression of gonadal activity was seen in the 7-h mice and a maximum suppression in the 8-h mice,
along with a significantly increased degree of gonadal development in the 12-h mice, as compared with the controls. In addition
to its known regulation of seasonal gonadal cycles, the relative position of two circadian neural oscillations may also affect
the rate of gonadal development during the attainment of puberty in mice. Moreover, the present study provides an experimental
paradigm to test the coincidence model of circadian oscillations. 相似文献
96.
Native disulfide bond formation in eukaryotes is dependent on protein-disulfide isomerase (PDI) and its homologs, which contain varying combinations of catalytically active and inactive thioredoxin domains. However, the specific contribution of PDI to the formation of new disulfides versus reduction/rearrangement of non-native disulfides is poorly understood. We analyzed the role of individual PDI domains in disulfide bond formation in a reaction driven by their natural oxidant, Ero1p. We found that Ero1p oxidizes the isolated PDI catalytic thioredoxin domains, A and A' at the same rate. In contrast, we found that in the context of full-length PDI, there is an asymmetry in the rate of oxidation of the two active sites. This asymmetry is the result of a dual effect: an enhanced rate of oxidation of the second catalytic (A') domain and the substrate-mediated inhibition of oxidation of the first catalytic (A) domain. The specific order of thioredoxin domains in PDI is important in establishing the asymmetry in the rate of oxidation of the two active sites thus allowing A and A', two thioredoxin domains that are similar in sequence and structure, to serve opposing functional roles as a disulfide isomerase and disulfide oxidase, respectively. These findings reveal how native disulfide folding is accomplished in the endoplasmic reticulum and provide a context for understanding the proliferation of PDI homologs with combinatorial arrangements of thioredoxin domains. 相似文献
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98.
Journal of Plant Research - Asteraceae (synonym as Compositae) is one of the largest angiosperm families among flowering plants comprising one-tenth of all agri-horticultural species grown across... 相似文献
99.
Lauren Ann Metskas Mohini Kulp Stylianos P. Scordilis 《Cellular & molecular biology letters》2010,15(3):507-516
Skeletal muscle is a plastic tissue with known gender dimorphism, especially at the metabolic level. A proteomic comparison
of male and female murine biceps brachii was undertaken, resolving an average of 600 protein spots of MW 15–150 kDa and pI
5–8. Twenty-six unique full-length proteins spanning 11 KOG groups demonstrated statistically significant (p<0.05) abundance
differences between genders; the majority of these proteins have metabolic functions. Identified glycolytic enzymes demonstrated
decreased abundance in females, while abundance differences in identified oxidative phosphorylation enzymes were specific
to the proteins rather than to the functional group as a whole. Certain cytoskeletal and stress proteins showed specific expression
differences, and all three phosphorylation states of creatine kinase showed significant decreased abundance in females. Expression
differences were significant but many were subtle (≤ 2-fold), and known hormonally-regulated proteins were not identified.
We conclude that while gender dimorphism is present in non-exercised murine skeletal muscle, the proteome comparison of male
and female biceps brachii in exercise-naive mice indicates subtle differences rather than a large or obviously hormonal dimorphism. 相似文献
100.
Faik N. Musayev Martino L. Di Salvo Mario A. Saavedra Roberto Contestabile Mohini S. Ghatge Alexina Haynes Verne Schirch Martin K. Safo 《The Journal of biological chemistry》2009,284(45):30949-30956
Mutations in pyridoxine 5′-phosphate oxidase are known to cause neonatal epileptic encephalopathy. This disorder has no cure or effective treatment and is often fatal. Pyridoxine 5′-phosphate oxidase catalyzes the oxidation of pyridoxine 5′-phosphate to pyridoxal 5′-phosphate, the active cofactor form of vitamin B6 required by more than 140 different catalytic activities, including enzymes involved in amino acid metabolism and biosynthesis of neurotransmitters. Our aim is to elucidate the mechanism by which a homozygous missense mutation (R229W) in the oxidase, linked to neonatal epileptic encephalopathy, leads to reduced oxidase activity. The R229W variant is ∼850-fold less efficient than the wild-type enzyme due to an ∼192-fold decrease in pyridoxine 5′-phosphate affinity and an ∼4.5-fold decrease in catalytic activity. There is also an ∼50-fold reduction in the affinity of the R229W variant for the FMN cofactor. A 2.5 Å crystal structure of the R229W variant shows that the substitution of Arg-229 at the FMN binding site has led to a loss of hydrogen-bond and/or salt-bridge interactions between FMN and Arg-229 and Ser-175. Additionally, the mutation has led to an alteration of the configuration of a β-strand-loop-β-strand structure at the active site, resulting in loss of two critical hydrogen-bond interactions involving residues His-227 and Arg-225, which are important for substrate binding and orientation for catalysis. These results provide a molecular basis for the phenotype associated with the R229W mutation, as well as providing a foundation for understanding the pathophysiological consequences of pyridoxine 5′-phosphate oxidase mutations. 相似文献