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1.
The loss of epidermal growth factor (EGF) binding activity on cultured murine 3T3 cells exposed to EGF (EGF receptor down regulation) was determined in colchicine treated cells, cytochalasin B treated cells, and untreated cells. Neither colchicine nor cytochalasin B altered the affinity of the receptor for EGF, but colchicine decreased maximal EGF binding activity by 20%. The maximal extent of EGF receptor down regulation was similar in colchicine treated cells and cytochalasin B treated cells, but the rate of receptor down regulation was higher in cytochalasin B treated cells. Cytoplasts produced by subjecting cytochalasin B treated cells adhering to the substratum to centrifugal force responded to EGF with nearly normal down regulation kinetics. The results suggest that the cytoskeleton is not obligatorily involved in EGF-induced EGF receptor down regulation.  相似文献   

2.
Data from the literature and own ones indicate the key role of the nervous system in regulation of the activity and synthesis of the enzymes of energy metabolism in skeletal muscles. Hepatic cells are highly sensitive both to regulation of their metabolism by the vegetative, especially sympathetic nervous system, and hormonal regulation. The enzymic activity and metabolism in the kidneys are controlled mainly by hormones and are not subjected or poorly monitored by the nervous system. Hormonal regulation of the enzymic activity in the bone marrow is presumably rather poor, whereas the question of nervous regulation of its metabolism remains nuclear.  相似文献   

3.
The plasminogen-activator system provides proteolytic activity in many biological processes. The regulation of plasminogen activation may occur at many levels including the synthesis and secretion of plasminogen activators (PA) and the specific inhibition of PA activity by inhibitors. PA-inhibitor type-1 (PAI-1) is an efficient inhibitor of tissue-type PA (tPA) and urokinase-type PA (uPA) that may therefore be instrumental for the control of plasminogen activation. To investigate if coordinated regulation of PA and PA inhibitors take place in vivo in response to physiological signals, we have examined the regulation of PAI-1 and tPA in the ovary during gonadotropin-induced ovulation. We found that PAI-1, as well as tPA activity and mRNA levels, were coordinately regulated by gonadotropins in a time-dependent and cell-specific manner, such that a surge of PA-activity was obtained just prior to ovulation. Both theca-interstitial and granulosa cells synthesized PAI-1, but their maximal PAI-1 expression occurred at different times during the periovulatory period, ensuring inhibition of proteolytic activity in ovarian extra cellular compartments both before and after ovulation. The coordinated regulation of tPA and PAI-1 in the ovary may fine-tune the peak of PA activity which may be important for the regulation of the ovulatory process.  相似文献   

4.
The regulation of aromatase activity by cAMP and FSH has been demonstrated in the prepubertal rat testis and ovary, and the question posed whether this regulation was already operative at foetal stages. In the present study, testes and ovaries from 17- to 21-day-old rat foetuses were cultured in vitro in the presence of [3H]-testosterone and in the presence or absence of cAMP or FSH. Oestrone and oestradiol formed from [3H]-testosterone were measured by double isotopic dilution and recrystallization to constant specific activity. Aromatase activity was augmented in both gonads by cAMP, but only in the testis by FSH. Thus, the regulation of aromatase activity by FSH begins earlier in the testis than in the ovary.  相似文献   

5.
Cairney CJ  Keith WN 《Biochimie》2008,90(1):13-23
Telomerase activity is dependent on the expression of 2 main core component genes, hTERT, which encodes the catalytic component and hTR (also called TERC), which encodes the RNA component. The correlation between telomerase activity and carcinogenesis has made this molecule of great interest in cancer research, however in order to fully understand the regulation of telomerase the mechanisms controlling both telomerase genes need to be studied. Some of these mechanisms of regulation have begun to emerge, however many more remain to be deciphered. For many years hTERT has been regarded as the limiting component of telomerase and much of the research in this field has focussed on its regulation, however it was clear from an early stage that hTR expression was also tightly regulated in normal cells and disease. More recently evidence from biochemistry, promoter studies and mouse models has been steadily increasing for a role for hTR as a limiting and essential component for telomerase activity and telomere maintenance. Perhaps the time has come to redefine our view of telomerase regulation. Knowledge of the mechanisms controlling both telomerase genes in normal systems and cancer may aid our understanding of the role of telomerase in carcinogenesis or highlight potential areas for therapeutic intervention. Here we review the essential requirement of hTR for telomere maintenance and telomerase activity in normal tissues and disease and focus on recent advances in our understanding of hTR regulation in relation to hTERT.  相似文献   

6.
莱茵藻胞外碳酸酐酶分子定位与活性诱导   总被引:5,自引:1,他引:4  
胞外碳酸酐酶是藻类CCM机制和光合作用的一个重要组分 ,藻类从高CO2 转入低CO2 浓度培养时可诱导出胞外碳酸酐酶。应用金标免疫分子定位和pH调节对胞外碳酸酐酶分子定位和CO2 诱导机制进行研究 ,结果表明 :胞外碳酸酐酶主要分布于胞壁空间 (细胞质膜与细胞壁之间 ) ,且细胞壁上也有较多分布 ,细胞壁外分布较少。说明胞外碳酸酐酶能从胞壁空间穿过细胞壁。通过CO2 诱导和pH调节(升高 ) ,均可提高碳酸酐酶活性 ,且pH提高幅度越大 ,胞外碳酸酐酶活性也越大 ,说明胞外碳酸酐酶的CO2 诱导与pH调节有一定关系  相似文献   

7.
A prominent role for calcium/calmodulin-dependent protein kinase II (CaMKII) in regulation of excitatory synaptic transmission was proposed two decades ago when it was identified as a major postsynaptic density protein. Since then, fascinating mechanisms optimized to fine-tune the magnitude and locations of CaMKII activity have been revealed. The importance of CaMKII activity and autophosphorylation to synaptic plasticity in vitro, and to a variety of learning and memory paradigms in vivo has been demonstrated. Recent progress brings us closer to understanding the regulation of dendritic CaMKII activity, localization, and expression, and its role in modulating synaptic transmission and cell morphology.  相似文献   

8.
The specificity of the 26S proteasome endoribonuclease activity in proerythroleukemic K562 cells has been shown to change under the effects of inducers of erythroid differentiation inducers led to specific stimulation of RNase activity for certain mRNAs and to reduction of proteasome RNase activity for other mRNAs. The studied enzymatic activity was shown to be specifically and selectively dependent on phosphorylation of the 26S proteasome subunits, as well as on Mg and Ca ions. It was shown that the specificity of the proteasome RNase activity is regulated during differentiation and apoptosis. Selective regulation of the proteasome via the activities of different nuclease centers was suggested. This regulation may be accomplished through changes in the phosphorylation state of the proteasome subunits as well as by cation homeostasis.  相似文献   

9.
James CL  Viola RE 《Biochemistry》2002,41(11):3720-3725
The bifunctional enzyme aspartokinase-homoserine dehydrogenase I from Escherichia coli catalyzes non-consecutive reactions in the aspartate pathway of amino acid biosynthesis. Both catalytic activities are subject to allosteric regulation by the end product amino acid L-threonine. To examine the kinetics and regulation of the enzymes in this pathway, each of these catalytic domains were separately expressed and purified. The separated catalytic domains remain active, with each of their catalytic activities enhanced in comparison to the native enzyme. The allosteric regulation of the kinase activity is lost, and regulation of the dehydrogenase activity is dramatically decreased in these separate domains. To create a new bifunctional enzyme that can catalyze consecutive metabolic reactions, the aspartokinase I domain was fused to the enzyme that catalyzes the intervening reaction in the pathway, aspartate semialdehyde dehydrogenase. A hybrid bifunctional enzyme was also created between the native monofunctional aspartokinase III, an allosteric enzyme regulated by lysine, and the catalytic domain of homoserine dehydrogenase I with its regulatory interface domain still attached. In this hybrid the kinase activity remains sensitive to lysine, while the dehydrogenase activity is now regulated by both threonine and lysine. The dehydrogenase domain is less thermally stable than the kinase domain and becomes further destabilized upon removal of the regulatory domain. The more stable aspartokinase III is further stabilized against thermal denaturation in the hybrid bifunctional enzyme and was found to retain some catalytic activity even at temperatures approaching 100 degrees C.  相似文献   

10.
11.
胞外碳酸酐酶是藻类CCM机制和光合作用的一个重要组分,藻类从高CO2转入低CO2浓度培养时可诱导出胞外碳酸酐酶。应用金标免疫分子定位和pH调节对胞外碳酸酐酶分子定位和CO2诱导机制进行研究,结果表明:胞外碳酸酐酶主要分布于胞壁空间(细胞质膜与细胞壁之间),且细胞壁上也有较多分布,细胞壁外分布较少。说明胞外碳酸酐酶能从胞壁空间穿过细胞壁。通过CO2诱导和pH调节(升高),均可提高碳酸酐酶活性,且pH提高幅度越大,胞外碳酸酐酶活性也越大,说明胞外碳酸酐酶的CO2诱导与pH调节有一定关系。  相似文献   

12.
Since both transport activity and the leucine biosynthetic enzymes are repressed by growth on leucine, the regulation of leucine, isoleucine, and valine biosynthetic enzymes was examined in Escherichia coli K-12 strain EO312, a constitutively derepressed branched-chain amino acid transport mutant, to determine if the transport derepression affected the biosynthetic enzymes. Neither the iluB gene product, acetohydroxy acid synthetase (acetolactate synthetase, EC 4.1.3.18), NOR THE LEUB gene product, 3-isopropylmalate dehydrogenase (2-hydroxy-4-methyl-3-carboxyvalerate-nicotinamide adenine dinucleotide oxido-reductase, EC 1.1.1.85), were significantly affected in their level of derepression or repression compared to the parental strain. A number of strains with alterations in the regulation of the branched-chain amino acid biosynthetic enzymes were examined for the regulation of the shock-sensitive transport system for these amino acids (LIV-I). When transport activity was examined in strains with mutations leading to derepression of the iluB, iluADE, and leuABCD gene clusters, the regulation of the LIV-I transport system was found to be normal. The regulation of transport in an E. coli strain B/r with a deletion of the entire leucine biosynthetic operon was normal, indicating none of the gene products of this operon are required for regulation of transport. Salmonella typhimurium LT2 strain leu-500, a single-site mutation affecting both promotor-like and operator-like function of the leuABCD gene cluster, also had normal regulation of the LIV-I transport system. All of the strains contained leucine-specific transport activity, which was also repressed by growth in media containing leucine, isoleucine and valine. The concentrated shock fluids from these strains grown in minimal medium or with excess leucine, isoleucine, and valine were examined for proteins with leucine-binding activity, and the levels of these proteins were found to be regulated normally. It appears that the branched-chain amino acid transport systems and biosynthetic enzymes in E. coli strains K-12 and B/r and in S. typhimurium strain LT2 are not regulated together by a cis-dominate type of mechanism, although both systems may have components in common.  相似文献   

13.
The regulation of ribulose-1,5-bisphosphate (RuBP) carboxylase (Rubisco) activity and metabolite pool sizes in response to natural diurnal changes in photon flux density (PFD) was examined in three species (Phaseolus vulgaris, Beta vulgaris, and Spinacia oleracea) known to differ in the mechanisms used for this regulation. Diurnal regulation of Rubisco activity in P. vulgaris was primarily the result of metabolism of the naturally occurring tight-binding inhibitor of Rubisco, 2-carboxyarabinitol 1-phosphate (CA1P). In B. vulgaris, the regulation of Rubisco activity was the result of both changes in activation state and CA1P metabolism. In S. oleracea, Rubisco activity was regulated by a combination of changes in activation state and the binding/release of another tight binding inhibitor, probably RuBP. Despite these different mechanisms for the light regulation of Rubisco activity, the relationship between the in vivo activity of Rubisco and the PFD was the same for all three species. Rates of CA1P metabolism were thus sufficient to allow this mechanism to participate in the diurnal regulation of Rubisco activity as PFD changed at its normal rate. Furthermore, under natural conditions this regulatory mechanism was found to be important in controlling Rubisco activity over approximately the same range of PFD as did changes in activation state of the enzyme. Finally, this regulation of Rubisco activity resulted in relatively similar and saturating RuBP pool sizes for photosynthesis at all but the lowest PFD values in all three species.  相似文献   

14.
The dimeric mammalian phosphodiesterases (PDEs) are regulated by N-terminal domains. In PDE5, the GAF-A subdomain of a GAF-tandem (GAF-A and -B) binds the activator cGMP and in PDE10 GAF-B binds cAMP. GAF-tandem chimeras of PDE5 and 10 in which the 36 aa linker helix between GAF-A and -B was swapped lost allosteric regulation of a reporter adenylyl cyclase. In 16 consecutive constructs we substituted the PDE10 linker with that from PDE5. An initial stretch of 10 amino acids coded for isoform specificity. A C240Y substitution uncoupled cyclase activity from regulation, whereas C240F, L or G did not. The C240Y substitution increased basal activity to stimulated levels. Notably, over the next 12 substitutions basal cyclase activity decreased linearly.Further targeted substitutions were based on homology modeling using the PDE2 structure. No combination of substitutions within the initial 10 linker residues caused loss of regulation. The full 10 aa stretch was required. Modeling indicated a potential interaction of the linker with a loop from GAF-A. To interrupt H-bonding a glycine substitution of the loop segment was generated. Despite reduction of basal activity, loss of regulation was maintained. Possibly, the orientation of the linker helix is determined by formation of the dimer at the initial linker segment. Downstream deflections of the linker helix may have caused loss of regulation.  相似文献   

15.
Nitrate is one of the most important stimuli in nitrate reductase (NR) induction, while ammonium is usually an inhibitor. We evaluated the influence of nitrate, ammonium or urea as nitrogen sources on NR activity of the agarophyte Gracilaria chilensis. The addition of nitrate rapidly (2 min) induced NR activity, suggesting a fast post-translational regulation. In contrast, nitrate addition to starved algae stimulated rapid nitrate uptake without a concomitant induction of NR activity. These results show that in the absence of nitrate, NR activity is negatively affected, while the nitrate uptake system is active and ready to operate as soon as nitrate is available in the external medium, indicating that nitrate uptake and assimilation are differentially regulated. The addition of ammonium or urea as nitrogen sources stimulated NR activity after 24 h, different from that observed for other algae. However, a decrease in NR activity was observed after the third day under ammonium or urea. During the dark phase, G. chilensis NR activity was low when compared to the light phase. A light pulse of 15 min during the dark phase induced NR activity 1.5-fold suggesting also fast post-translational regulation. Nitrate reductase regulation by phosphorylation and dephosphorylation, and by protein synthesis and degradation, were evaluated using inhibitors. The results obtained for G. chilensis show a post-translational regulation as a rapid response mechanism by phosphorylation and dephosphorylation, and a slower mechanism by regulation of RNA synthesis coupled to de novo NR protein synthesis.  相似文献   

16.
Endothelium plays a fundamental role in maintaining the vascular tone by releasing various biochemical factors that modulate the contractile and relaxatory behavior of the underlying vascular smooth muscle, regulation of inflammation, immunomodulation, platelet aggregation, and thrombosis. Endothelium regulates these cellular processes by activating endothelial nitric oxide synthase (eNOS) responsible for nitric oxide (NO) production. eNOS is constitutively expressed in ECs in response to humoral, mechanical or pharmacological stimulus. eNOS activity is regulated mainly by protein-protein interactions and multisite phosphorylations. The phosphorylation state of specific serine, threonine and tyrosine residues of the enzyme plays a pivotal role in regulation of eNOS activity. Perturbations of eNOS phosphorylation have been reported in a number of diseases thereby emphasizing the importance of regulation of eNOS activity. This review summarizes the mechanism of eNOS regulation through multi-site phosphorylation in different pathologies. Attempts have been made to highlight phosphorylation of eNOS at various residues, regulation of the enzyme activity via posttranslational modifications and its implications on health and disease.  相似文献   

17.
1. Pyruvate dehydrogenase phosphate phosphatase activity in rat epididymal fat-pads was measured by using pig heart pyruvate dehydrogenase [32P]phosphate. About 80% was found to be extramitochondrial and therefore probably not directly concerned with the regulation of pyruvate dehydrogenase activity. The extramitochondrial activity was sensitive to activation by Ca2+, but perhaps less sensitive than the mitochondrial activity.  相似文献   

18.
Efficiency of substrates for cholesterol esterase (EC 3.1.1.13) assay, and regulation of the activity were investigated in rat epididymal adipose tissue. The activity in the supernatant was activated by cyclic AMP-dependent protein kinase, cyclic AMP, ATP and Mg2+, both with micellar and liposomal substrates. However, the micellar substrate was more suitable for the assay than the liposomal with respect to Vmax and Km. Thus, the micellar substrate was employed. Pretreatment of the supernatant with exogenous cyclic AMP-dependent protein kinase enhanced the activity dose dependently, whereas that with cyclic AMP decreased the activity slightly. The cyclic AMP-dependent protein kinase activity in the assay mixture was within the range which can cause changes in cholesterol esterase activity. These results suggest that the amount of cyclic AMP-dependent protein kinase, rather than the cyclic AMP level, plays an important role in the regulation of cholesterol esterase in tissues with a high cholesterol esterase activity relative to the kinase activity, such as in adipose tissue.  相似文献   

19.
Regulation of low-density-lipoprotein-receptor activity by low-density lipoprotein (LDL), cholesteryl-ester-rich beta-migrating very-low-density lipoprotein (beta-VLDL) and non-lipoprotein cholesterol was investigated in the human hepatoma cell line Hep G2. Competition studies indicate that LDL and beta-VLDL are bound to the same recognition site, tentatively the LDL receptor. The regulatory response of the LDL receptor upon prolonged incubation with LDL or beta-VLDL was, however, markedly different. 22 h preincubation of Hep G2 cells with excess LDL caused a partial down regulation to 31% of the initial level of the high-affinity association of LDL and 26% of the high-affinity degradation of LDL, while with beta-VLDL a complete down regulation of the LDL-receptor activity is observed. Preincubation of Hep G2 cells with beta-VLDL for 22 h led to a fourfold increase in intracellular cholesterol esters and a twofold increase in acyl-coA:cholesterol acyltransferase activity. With LDL, the amount of intracellular cholesterol esters is increased 1.6-fold. The more effective down regulation of LDL receptors by beta-VLDL as compared to LDL can be explained by the more effective intracellular cholesterol delivery with beta-VLDL than with LDL. Preincubation of Hep G2 cells for 22 h with acetylated LDL hardly influenced the LDL-receptor activity. Non-lipoprotein cholesterol, however, caused a complete down regulation of LDL-receptor activity at even lower extracellular cholesterol concentrations than with beta-VLDL. The complete down regulation of LDL receptors by non-lipoprotein cholesterol is not accompanied by a significant increase in acyl-coA:cholesterol acyltransferase activity, while the intracellular cholesterol ester concentration is only increased 1.6-fold. It is suggested that the effectiveness of non-lipoprotein cholesterol to regulate LDL receptors is caused by its efficiency to reach the sterol regulatory site. The inability of LDL to down regulate its receptor completely can thus be explained by the inability of LDL to deliver cholesterol adequately at the intracellular regulatory site of the LDL receptor. The observed complete down regulation of the LDL receptor by beta-VLDL may be responsible for the cholesterol-rich-diet induced, complete down regulation of LDL-receptor-mediated clearance of LDL in vivo.  相似文献   

20.
Sulfur regulation of heparinase and sulfatases in Flavobacterium heparinum   总被引:2,自引:0,他引:2  
Sulfur regulation of heparinase synthesis and sulfatase synthesis was studied in Flavobacterium heparinum. Heparinase synthesis was strongly repressed by sulfate and L-cysteine, while the activity of this enzyme showed little or no inhibition by these compounds. Heparinase was synthesized in the absence of heparin when L-methionine was used as the sole sulfur source. The sulfatases produced by F. heparinum, which include the sulfatases involved in heparin catabolism, were also studied. At least some of the sulfatase activity was regulated by sulfur compounds in a manner similar to heparinase regulation. L-Cysteic acid and taurine were not suitable sulfur sources to support the growth of F. heparinum.  相似文献   

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