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141.
Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load 总被引:19,自引:0,他引:19
We have investigated the effects of insulin, amino acids, and the degree of muscle loading on the phosphorylation of Ser(2448), a site in the mammalian target of rapamycin (mTOR) phosphorylated by protein kinase B (PKB) in vitro. Phosphorylation was assessed by immunoblotting with a phosphospecific antibody (anti-Ser(P)(2448)) and with mTAb1, an activating antibody whose binding is inhibited by phosphorylation in the region of mTOR that contains Ser(2448). Incubating rat diaphragm muscles with insulin increased Ser(2448) phosphorylation but did not change the total amount of mTOR. Insulin, but not amino acids, activated PKB, as evidenced by increased phosphorylation of both Ser(308) and Thr(473) in the kinase. Ser(2448) phosphorylation was also modulated by muscle-loading. Overloading the rat plantaris muscle by synergist muscle ablation, which promotes hypertrophy of the plantaris muscle, increased Ser(2448) phosphorylation. In contrast, unloading the gastrocnemius muscle by hindlimb suspension, which promotes atrophy of the muscle, decreased Ser(2448) phosphorylation, an effect that was fully reversible. Neither overloading nor hindlimb suspension significantly changed the total amount of mTOR. In summary, our results demonstrate that atrophy and hypertrophy of skeletal muscle are associated with decreases and increases in Ser(2448) phosphorylation, suggesting that modulation of this site may have an important role in the control of protein synthesis. 相似文献
142.
The taste perception of monosodium glutamate (MSG) is termed 'umami'. Two putative taste receptors for glutamate have been identified, a truncated form of mGluR4 (taste-mGluR4) and the presumed heterodimer T1R1 + T1R3. Both receptors respond to glutamate when expressed in heterologous cells, but the G protein involved is not known. Galpha-Gustducin mediates the transduction of several bitter and sweet compounds; however, its role in umami has not been determined. We used standard two-bottle preference tests on alpha-gustducin knockout (KO) and wildtype (WT) mice to compare preferences for ascending concentrations of MSG and MSG + 5'-inosine monophosphate (IMP). A Latin Square was used to assign the order of tastants presented to each mouse. Statistical comparisons between KO and WT mice revealed that whereas WT mice preferred solutions of MSG and MSG + IMP over water, KO mice showed little preference for these stimuli. Denatonium and sucrose served as control stimuli and, as shown previously, WT mice prefered sucrose and avoided denatonium significantly more than did KO mice. Na?ve mice were also tested, and while prior exposure to taste stimuli influenced the magnitude of the preferences, experience did not change the overall pattern of intake. These data suggest that alpha-gustducin plays a role in glutamate taste. 相似文献
143.
Excessive generation of reactive oxygen species (ROS) in the central nervous system (CNS) is a leading cause of neuronal injury. Despite yet unknown mechanisms, oxidant compounds such as H2O2 have been shown to stimulate the release of arachidonic acid (AA) in a number of cell systems. In this study, H2O2 and menadione, a compound known to release H2O2 intracellularly, were used to examine the phospholipases A2 (PLA2) responsible for AA release from primary murine astrocytes. Both H2O2 and menadione dose-dependently stimulated AA release, and the release mediated by H2O2 was completely inhibited by catalase. H2O2 also stimulated phosphorylation of extracellular signal-regulated kinases (ERK1/2) and cytosolic phospholipase A2 (cPLA2). However, complete inhibition of cPLA2 phosphorylation by U0126, an inhibitor for mitogen-activated protein kinase kinase (MEK) and GF109203x, a nonselective PKC inhibitor preferring the conventional and novel isoforms, only reduced H2O2-stimulated AA release by 50%. MAFP, a selective, active, site-directed, irreversible inhibitor of both cPLA2 and the Ca2+-independent iPLA2, nearly completely inhibited H2O2-mediated AA release; but, HELSS, a potent irreversible inhibitor of iPLA2, only inhibited H2O2-mediated AA release by 40%. Along with the observation that H2O2-mediated AA release was only partially inhibited upon chelating intracellular Ca2+ by BAPTA, these results indicate the involvement of both cPLA2 and iPLA2 in H2O2-mediated AA release in murine astrocytes. 相似文献
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Tyson J Tranebjaerg L McEntagart M Larsen LA Christiansen M Whiteford ML Bathen J Aslaksen B Sørland SJ Lund O Pembrey ME Malcolm S Bitner-Glindzicz M 《Human genetics》2000,107(5):499-503
Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterised by profound congenital sensorineural deafness and prolongation of the QT interval on the electrocardiogram, representing abnormal ventricular repolarisation. In a study of ten British and Norwegian families with JLNS, we have identified all of the mutations in the KCNQ1 gene, including two that are novel. Of the nine mutations identified in this group of 10 families, five are nonsense or frameshift mutations. Truncation of the protein proximal to the recently identified C-terminal assembly domain is expected to preclude assembly of KCNQ1 monomers into tetramers and explains the recessive inheritance of JLNS. However, study of a frameshift mutation, with a dominant effect phenotypically, suggests the presence of another assembly domain nearer to the N-terminus. 相似文献
147.
Sister chromatid cohesion is essential for accurate chromosome segregation during the cell cycle. Newly identified structural proteins are required for sister chromatid cohesion and there may be a link in some organisms between the processes of cohesion and condensation. Proteins that induce and regulate the separation of sister chromatids have also been recently identified. 相似文献
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Linda Sue Warner 《Anthropology & education quarterly》1998,29(4):498-499
Collaborative Research Stories: Whakawhanaungatanga. Russell Bishop. Palmerston North, New Zealand: Dunmore Press, 1996. 273 pp. 相似文献