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901.
Transformation of mouse fibroblasts by Jaagsiekte sheep retrovirus envelope does not require phosphatidylinositol 3-kinase 下载免费PDF全文
Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma, a transmissible lung cancer of sheep. The envelope of JSRV may have oncogenic properties, since it can morphologically transform mouse NIH 3T3 cells and other fibroblast lines. Recently, we found that the cytoplasmic tail of the envelope transmembrane (TM) protein is necessary for transformation, and in particular a consensus binding motif (YXXM) for phosphatidylinositol 3-kinase (PI3K) is important. Moreover, JSRV-transformed cells show phosphorylation (activation) of Akt/protein kinase B, a downstream target of PI3K. In these studies, we directly tested for the involvement of PI3K in transformation by JSRV. Contrary to expectations, four different experiments indicated that PI3K is not necessary for JSRV-induced transformation: (i) cotransfection with a dominant negative truncated form of the PI3K regulatory subunit (Deltap85) did not affect transformation frequency, (ii) cells stably expressing Deltap85 showed the same frequencies of transformation as parental NIH 3T3 cells, (iii) fibroblasts established from double-knockout mice lacking PI3K p85alpha and p85beta could be transformed with JSRV envelope, and (iv) incubation of cells with the PI3K inhibitor LY294002 did not specifically inhibit transformation, nor did the drug reverse transformation of JSRV-transformed cells. One alternate explanation for the lack of transformation by YXXM mutants could be that they were defective in intracellular trafficking. However, confocal microscopy of epitope-tagged envelope proteins of both wild-type and nontransforming YXXM mutants showed a cell surface or plasma membrane localization. While PI3K is not required for JSRV-induced transformation of NIH 3T3 cells, the downstream target Akt kinase was found to be activated (phosphorylated) in JSRV-transformed PI3K-negative cells. Therefore, JSRV envelope can induce PI3K-independent phosphorylation of Akt. 相似文献
902.
903.
Suzuki J Kato A Maeda N Hashimoto C Uchikoshi M Mizutani T Doke C Matsuzawa T 《Primates; journal of primatology》2003,44(3):273-280
We examined growth changes in concentrations of plasma insulin-like growth factor-1 (IGF-1) and testosterone, and somatometric
parameters in two captive male agile gibbons from birth to about 4 years of age, to examine the evolution of growth patterns
in primates. Plasma IGF-1 concentrations in agile gibbons generally increased with age with values ranging from 200 to 1,100 ng/ml.
The growth profiles in plasma IGF-1 in the gibbons were similar to those reported for chimpanzees. The highest concentrations
of plasma testosterone (230 and 296 ng/dl) were observed within the first 0.3 years from birth, then the concentrations rapidly
decreased and fluctuated below 100 ng/dl. Continuously higher IGF-1 concentrations were observed after 2.6 and 3.5 years of
age. The profiles of plasma testosterone in these gibbons also resembled those of other primates including humans. However,
their plasma testosterone levels in both neonate and adult stages (60 ng/dl) were lower than those reported for macaques and
chimpanzees of respective stages. The obtained growth profiles of plasma IGF-1 and testosterone suggest that the adolescent
phase starts around 2.6 or 3.5 years of age in male agile gibbons. The growth trend in many morphological parameters including
body weight showed a linear increase without a significant growth spurt at approximately the onset of puberty. Head length
and first digit length had reached a plateau during the study period. Brachial index, which indicates the relative length
of forearm to upper arm, significantly increased gradually through the growth period. This result indicates that forearm becomes
relatively longer than the upper arm with growth, which may be an evolutionary adaptation for brachiation. 相似文献
904.
905.
Phosphorelay-regulated degradation of the yeast Ssk1p response regulator by the ubiquitin-proteasome system 总被引:4,自引:0,他引:4 下载免费PDF全文
In Saccharomyces cerevisiae, a phosphorelay signal transduction pathway composed of Sln1p, Ypd1p, and Ssk1p, which are homologous to bacterial two-component signal transducers, is involved in the osmosensing mechanism. In response to high osmolarity, the phosphorelay system is inactivated and Ssk1p remains unphosphorylated. Unphosphorylated Ssk1p binds to and activates the Ssk2p mitogen-activated protein (MAP) kinase kinase kinase, which in turn activates the downstream components of the high-osmolarity glycerol response (HOG) MAP kinase cascade. Here, we report a novel inactivation mechanism for Ssk1p involving degradation by the ubiquitin-proteasome system. Degradation is regulated by the phosphotransfer from Ypd1p to Ssk1p, insofar as unphosphorylated Ssk1p is degraded more rapidly than phosphorylated Ssk1p. Ubc7p/Qri8p, an endoplasmic reticulum-associated ubiquitin-conjugating enzyme, is involved in the phosphorelay-regulated degradation of Ssk1p. In ubc7Delta cells in which the degradation is hampered, the dephosphorylation and/or inactivation process of the Hog1p MAP kinase is delayed compared with wild-type cells after the hyperosmotic treatment. Our results indicate that unphosphorylated Ssk1p is selectively degraded by the Ubc7p-dependent ubiquitin-proteasome system and that this mechanism downregulates the HOG pathway after the completion of the osmotic adaptation. 相似文献
906.
907.
Ozeki Y Chikagawa Y Kimura S Soh HC Maeda K Pornsiriwong W Kato M Akimoto H Oyanagi M Fukuda T Koda T Itoh Y Yamada A Davies E Ueno H Takeda J 《Journal of plant research》2003,116(2):155-159
Deletion mutants of the carrot phenylalanine ammonia-lyase gene promoter were used to survey cis-elements for their effect on expression of promoter activity by transient expression. Two putative cis-elements were required to give full activity, but a third might be the most important in regulation of the promoter by 2,4-dichlorophenoxyacetic
acid.
Electronic Publication 相似文献
908.
Tanaka S Kinowaki M Eto TA Ota Y Maeda Y Okuda K Setoguchi T Chijiiwa K 《The Journal of steroid biochemistry and molecular biology》2003,86(1):35-40
Cholesterol 7alpha-hydroxylase (cholesterol-NADPH oxidoreductase, EC 1.14.13.17, 7alpha-hydroxylating) is known to have extremely sensitive sulfhydryl group(s). It is believed that a cysteine residue that has a sulfhydryl group plays an important role in the decrease of this enzyme activity. The amino acid sequences of cholesterol 7alpha-hydroxylase of five different mammalian species, human, rat, rabbit, hamster and mouse, revealed that these mammalian species contain eight cysteine residues that are well conserved. To identify which cysteine residues are responsible for the extremely high lability, we used the technique of the site-directed mutagenesis. Eight mutated genes of human cholesterol 7alpha-hydroxylase in which one codon for a cysteine residue was changed to that for alanine were prepared and expressed in COS-1 cells. The protein mass and enzyme activity of cholesterol 7alpha-hydroxylse obtained from these eight mutated genes were determined. While all mutated genes expressed the enzyme mass, two mutated genes did not express protein capable of catalyzing 7alpha-hydroxylation of cholesterol: in one mutant a codon for the 7th cysteine residue (Cys 444) was substituted to that for alanine and in the other mutant a codon for the 8th cysteine residue (Cys 476) was changed similarly. These results suggest that the 7th and 8th cysteine residues are important for expression of the enzyme activity. Based on the fact that Cys 444 exists in the heme binding region, Cys 476 was suggested to be responsible for enzyme lability. 相似文献
909.
Role of the polypeptide region of a 33kDa mycobacterial lipoprotein for efficient IL-12 production 总被引:1,自引:0,他引:1
Mycobacterium leprae lipoprotein, LpK, induced IL-12 production from human monocytes. To determine the components essential for cytokine production and the relative role of lipidation in the activation process, we produced lipidated and non-lipidated truncated forms of LpK. While 0.5nM of lipidated LpK-a having N-terminal 60 amino acids of LpK produced more than 700pg/ml IL-12 p40, the non-lipidated LpK-b having the same amino acids as that of LpK-a required more than 20nM of the protein to produce an equivalent dose of cytokine. Truncated protein having the C-terminal 192 amino acids of LpK did not induce any cytokine production. Fifty nanomolar of the synthetic lipopeptide of LpK produced only about 200pg/ml IL-12. Among the truncated LpK, only LpK-a and lipopeptide stimulated NF-kB-dependent reporter activity in TLR-2 transfectant. However, when monocytes were stimulated with lipopeptide in the presence of non-lipidated protein, they produced IL-12 synergistically. Therefore, both peptide regions of LpK and lipid residues are necessary for efficient IL-12 production. 相似文献
910.