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排序方式: 共有142条查询结果,搜索用时 15 毫秒
81.
Arden C Green AR Hampson LJ Aiston S Härndahl L Greenberg CC Brady MJ Freeman S Poucher SM Agius L 《The FEBS journal》2006,273(9):1989-1999
Hepatic insulin resistance in the leptin-receptor defective Zucker fa/fa rat is associated with impaired glycogen synthesis and increased activity of phosphorylase-a. We investigated the coupling between phosphorylase-a and glycogen synthesis in hepatocytes from fa/fa rats by modulating the concentration of phosphorylase-a. Treatment of hepatocytes from fa/fa rats and Fa/? controls with a selective phosphorylase inhibitor caused depletion of phosphorylase-a, activation of glycogen synthase and stimulation of glycogen synthesis. The flux-control coefficient of phosphorylase on glycogen synthesis was glucose dependent and at 10 mm glucose was higher in fa/fa than Fa/? hepatocytes. There was an inverse correlation between the activities of glycogen synthase and phosphorylase-a in both fa/fa and Fa/? hepatocytes. However, fa/fa hepatocytes had a higher activity of phosphorylase-a, for a corresponding activity of glycogen synthase. This defect was, in part, normalized by expression of the glycogen-targeting protein, PTG. Hepatocytes from fa/fa rats had normal expression of the glycogen-targeting proteins G(L) and PTG but markedly reduced expression of R6. Expression of R6 protein was increased in hepatocytes from Wistar rats after incubation with leptin and insulin. Diminished hepatic R6 expression in the leptin-receptor defective fa/fa rat may be a contributing factor to the elevated phosphorylase activity and/or its high control strength on glycogen synthesis. 相似文献
82.
Myosin VI isoform localized to clathrin-coated vesicles with a role in clathrin-mediated endocytosis. 总被引:6,自引:0,他引:6
Myosin VI is involved in membrane traffic and dynamics and is the only myosin known to move towards the minus end of actin filaments. Splice variants of myosin VI with a large insert in the tail domain were specifically expressed in polarized cells containing microvilli. In these polarized cells, endogenous myosin VI containing the large insert was concentrated at the apical domain co-localizing with clathrin- coated pits/vesicles. Using full-length myosin VI and deletion mutants tagged with green fluorescent protein (GFP) we have shown that myosin VI associates and co-localizes with clathrin-coated pits/vesicles by its C-terminal tail. Myosin VI, precipitated from whole cytosol, was present in a protein complex containing adaptor protein (AP)-2 and clathrin, and enriched in purified clathrin-coated vesicles. Over-expression of the tail domain of myosin VI containing the large insert in fibroblasts reduced transferrin uptake in transiently and stably transfected cells by >50%. Myosin VI is the first motor protein to be identified associated with clathrin-coated pits/vesicles and shown to modulate clathrin-mediated endocytosis. 相似文献
83.
Mukhtar MH Payne VA Arden C Harbottle A Khan S Lange AJ Agius L 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,294(3):R766-R774
The rate of glucose phosphorylation in hepatocytes is determined by the subcellular location of glucokinase and by its association with its regulatory protein (GKRP) in the nucleus. Elevated glucose concentrations and precursors of fructose 1-phosphate (e.g., sorbitol) cause dissociation of glucokinase from GKRP and translocation to the cytoplasm. In this study, we investigated the counter-regulation of substrate-induced translocation by AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside), which is metabolized by hepatocytes to an AMP analog, and causes activation of AMP-activated protein kinase (AMPK) and depletion of ATP. During incubation of hepatocytes with 25 mM glucose, AICAR concentrations below 200 microM activated AMPK without depleting ATP and inhibited glucose phosphorylation and glucokinase translocation with half-maximal effect at 100-140 microM. Glucose phosphorylation and glucokinase translocation correlated inversely with AMPK activity. AICAR also counteracted translocation induced by a glucokinase activator and partially counteracted translocation by sorbitol. However, AICAR did not block the reversal of translocation (from cytoplasm to nucleus) after substrate withdrawal. Inhibition of glucose-induced translocation by AICAR was greater than inhibition by glucagon and was associated with phosphorylation of both GKRP and the cytoplasmic glucokinase binding protein, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2) on ser-32. Expression of a kinase-active PFK2 variant lacking ser-32 partially reversed the inhibition of translocation by AICAR. Phosphorylation of GKRP by AMPK partially counteracted its inhibitory effect on glucokinase activity, suggesting altered interaction of glucokinase and GKRP. In summary, mechanisms downstream of AMPK activation, involving phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and GKRP are involved in the ATP-independent inhibition of glucose-induced glucokinase translocation by AICAR in hepatocytes. 相似文献
84.
85.
Arden KC 《Molecular cell》2004,14(4):416-418
Two recent reports reveal new roles for FoxO proteins in cell proliferation and tumorigenesis. Seoane and colleagues show that FoxO proteins play key roles in the TGFbeta-dependent activation of p21Cip1 by partnering with Smad3 and Smad4. FoxG1, a protein from a distinct Fox subfamily, binds FoxO/Smad complexes and blocks p21Cip1 expression. These interactions establish a relationship between the PI3K pathway, FoxG1, and the TGFbeta/Smad pathways. The second report identifies IkappaB kinase as a negative regulator of FoxO proteins, suggesting a mechanism for relieving negative regulation of cell cycle and promoting tumor cell proliferation. 相似文献
86.
87.
Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor 总被引:154,自引:0,他引:154
Brunet A Bonni A Zigmond MJ Lin MZ Juo P Hu LS Anderson MJ Arden KC Blenis J Greenberg ME 《Cell》1999,96(6):857-868
88.
Mouse T-cell receptor variable gene segment families 总被引:16,自引:3,他引:13
All mouse T-cell receptor /, , and variable (Tcra/d, b-, and g-V) gene segments were aligned to compare the sequences with one another, to group them into subfamilies, and to derive a name which complies with the standard nomenclature. It was necessary to change the names of some V gene segments because they conflicted with those of other segments. The traditional classification into subfamilies was re-evaluated using a much larger pool of sequences. In the mouse, most V gene segments can be grouped into subfamilies of closely related genes with significantly less similarity between different subfamilies.The alignment data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the alignment number DS23485. The data are available by the EBI FTP server and file serverCorrespondence with corrections or new information concerning the TCRV sequences is strongly encouraged. 相似文献
89.
Human T-cell receptor variable gene segment families 总被引:38,自引:3,他引:35
Multiple DNA and protein sequence alignments have been constructed for the human T-cell receptor /, , and (TCRA/D, B, and G) variable (V) gene segments. The traditional classification into subfamilies was confirmed using a much larger pool of sequences. For each sequence, a name was derived which complies with the standard nomenclature. The traditional numbering of V gene segments in the order of their discovery was continued and changed when in conflict with names of other segments. By discriminating between alleles at the same locus versus genes from different loci, we were able to reduce the number of more than 150 different TCRBV sequences in the database to a repertoire of only 47 functional TCRBV gene segments. An extension of this analysis to the over 100 TCRAV sequences results in a predicted repertoire of 42 functional TCRAV gene segments. Our alignment revealed two residues that distinguish between the highly homologous V and V, one at a site that in VH contacts the constant region, the other at the interface between immunoglobulin VH and VL. This site may be responsible for restricted pairing between certain V and V chains. On the other hand, V and V appear to be related by the fact that their CDR2 legnth is increased by four residues as compared with that of V/ peptides.The alignment data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the aligmment number DS23485. The data are available by the EBI FTP server and file serverCorrespondence with corrections or new information concerning the TCRV sequences is strongly encouraged. 相似文献
90.
Short/branched chain acyl-CoA dehydrogenase, SBCAD (gene symbol ACADSB), is a member of the acyl-CoA dehydrogenase family of genes with activity toward the short/branched chain acyl-CoA derivatives as well as short/straight chain acyl-CoAs. Southern blot analysis of DNA from a panel of human/rodent somatic cell hybrids localized ACADSB to human chromosome 10, and fluorescence in situ hybridization experiments confirmed the chromosomal assignment and refined the subchromosomal localization to 10q25–q26. 相似文献