{"title":"Going Against the Flow","authors":"Philip Ball","doi":"10.1038/NEWS020624-1","DOIUrl":"https://doi.org/10.1038/NEWS020624-1","url":null,"abstract":"","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"15 1","pages":"tw144 - tw144"},"PeriodicalIF":0.0,"publicationDate":"2002-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84901738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-03-26DOI: 10.1126/scisignal.1252002tw121
Tumor necrosis factor-α (TNF-α), otherwise known as a proinflammatory cytokine, turns out to be active on a continual basis in the nervous system. Beattie et al., studied synaptic function in cultured hippocampal neurons and hippocampal brain slices and showed that TNF-α promotes expression of a neurotransmitter receptor on the cell surfaces at synapses. TNF-α is required continuously, suggesting that it may contribute to rapid adjustment of receptor levels at a synapse. TNF-α is supplied by affiliated glial cells, once again reminding us that the glial cells, previously thought to be rather passive support partners, are important behind-the-scenes participants in neuronal function. E. C. Beattie, D. Stellwagen, W. Morishita, J. C. Bresnahan, B. K. Ha, M.Von Zastrow, M. S. Beattie, R. C. Malenka, Control of synaptic strength by glial TNF-α. Science 295, 2282-2285 (2002). [Abstract] [Full Text]
肿瘤坏死因子-α (TNF-α)，也被称为促炎细胞因子，在神经系统中持续活跃。Beattie等研究了培养海马神经元和海马脑切片的突触功能，发现TNF-α促进突触细胞表面一种神经递质受体的表达。TNF-α是持续需要的，这表明它可能有助于突触中受体水平的快速调节。TNF-α是由附属的神经胶质细胞提供的，这再次提醒我们，神经胶质细胞，以前被认为是相当被动的支持伙伴，在幕后是重要的神经元功能参与者。E. C. Beattie, D. Stellwagen, W. Morishita, J. C. Bresnahan, B. K. Ha, M. von Zastrow, M. S. Beattie, R. C. Malenka，神经胶质细胞TNF-α对突触强度的控制。科学295,2282-2285(2002)。【摘要】【全文】
{"title":"Neuronal Plasticity Promoted by Glia","authors":"","doi":"10.1126/scisignal.1252002tw121","DOIUrl":"https://doi.org/10.1126/scisignal.1252002tw121","url":null,"abstract":"Tumor necrosis factor-α (TNF-α), otherwise known as a proinflammatory cytokine, turns out to be active on a continual basis in the nervous system. Beattie et al., studied synaptic function in cultured hippocampal neurons and hippocampal brain slices and showed that TNF-α promotes expression of a neurotransmitter receptor on the cell surfaces at synapses. TNF-α is required continuously, suggesting that it may contribute to rapid adjustment of receptor levels at a synapse. TNF-α is supplied by affiliated glial cells, once again reminding us that the glial cells, previously thought to be rather passive support partners, are important behind-the-scenes participants in neuronal function. E. C. Beattie, D. Stellwagen, W. Morishita, J. C. Bresnahan, B. K. Ha, M.Von Zastrow, M. S. Beattie, R. C. Malenka, Control of synaptic strength by glial TNF-α. Science 295, 2282-2285 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"44 5","pages":"tw121 - tw121"},"PeriodicalIF":0.0,"publicationDate":"2002-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91552266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-03-26DOI: 10.1126/scisignal.1252002tw122
Neurotransmitter release is triggered by calcium influx through presynaptic voltage-dependent calcium channels. Modulation of presynaptic calcium currents causes a robust alteration in synaptic efficacy. Tsujimoto et al. investigated activity-dependent facilitation of P/Q-type calcium currents at the giant nerve terminals of the calyx of Held and found that calcium current up-regulation is mediated by the calcium-binding protein NCS-1, a homolog of the Drosophila frequenin protein. T. Tsujimoto, A. Jeromin, N. Saitoh, J. C. Roder, T. Takahashi, Neuronal calcium sensor 1 and activity-dependent facilitation of P/Q-type calcium current at presynaptic nerve terminals. Science 295: 2276-2279 (2002). [Abstract] [Full Text]
{"title":"Presynaptic Calcium Influx","authors":"","doi":"10.1126/scisignal.1252002tw122","DOIUrl":"https://doi.org/10.1126/scisignal.1252002tw122","url":null,"abstract":"Neurotransmitter release is triggered by calcium influx through presynaptic voltage-dependent calcium channels. Modulation of presynaptic calcium currents causes a robust alteration in synaptic efficacy. Tsujimoto et al. investigated activity-dependent facilitation of P/Q-type calcium currents at the giant nerve terminals of the calyx of Held and found that calcium current up-regulation is mediated by the calcium-binding protein NCS-1, a homolog of the Drosophila frequenin protein. T. Tsujimoto, A. Jeromin, N. Saitoh, J. C. Roder, T. Takahashi, Neuronal calcium sensor 1 and activity-dependent facilitation of P/Q-type calcium current at presynaptic nerve terminals. Science 295: 2276-2279 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"13 1","pages":"tw122 - tw122"},"PeriodicalIF":0.0,"publicationDate":"2002-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82059737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-03-19DOI: 10.1126/scisignal.1242002tw111
Mutations in the tumor suppressor protein PTEN occur in a variety of cancers. Its major enzymatic activity is to dephosphorylate phosphoinositides, including phosphoinositide-3,4,5-trisphosphate (PIP3). In the absence of PTEN, cellular levels of PIP3 increase, which result in overgrowth phenotypes and lethality in Drosophila larvae. However, PIP3 binds to numerous signaling molecules, and so it is not clear if there is a specific interaction that loss of PTEN function primarily affects. Stocker et al. show that flies can live in the absence of PTEN if the interaction of PIP3 with the serine-threonine kinase Akt is decreased through a mutation in its PH domain. At least in the fly, Akt appears to be the principal target of PIP3. H. Stocker, M. Andjelkovic, S. Oldham, M. Laffargue, M. P. Wymann, B. A. Hemmings, E. Hafen, Living with lethal PIP3 levels: Viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science 295, 2088-2091 (2002). [Abstract] [Full Text]
{"title":"Akt-ing Against a Loss","authors":"","doi":"10.1126/scisignal.1242002tw111","DOIUrl":"https://doi.org/10.1126/scisignal.1242002tw111","url":null,"abstract":"Mutations in the tumor suppressor protein PTEN occur in a variety of cancers. Its major enzymatic activity is to dephosphorylate phosphoinositides, including phosphoinositide-3,4,5-trisphosphate (PIP3). In the absence of PTEN, cellular levels of PIP3 increase, which result in overgrowth phenotypes and lethality in Drosophila larvae. However, PIP3 binds to numerous signaling molecules, and so it is not clear if there is a specific interaction that loss of PTEN function primarily affects. Stocker et al. show that flies can live in the absence of PTEN if the interaction of PIP3 with the serine-threonine kinase Akt is decreased through a mutation in its PH domain. At least in the fly, Akt appears to be the principal target of PIP3. H. Stocker, M. Andjelkovic, S. Oldham, M. Laffargue, M. P. Wymann, B. A. Hemmings, E. Hafen, Living with lethal PIP3 levels: Viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science 295, 2088-2091 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"3 1","pages":"tw111 - tw111"},"PeriodicalIF":0.0,"publicationDate":"2002-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90928245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-03-12DOI: 10.1126/scisignal.1232002tw103
The transcription factor CtBP associates with transcriptional repressors for the regulation of genes involved in development, cell cycle regulation, and transformation. Zhang et al. show that the corepressor activity of CtBP can be regulated by the redox state of the cell. Mammalian CtBP is regulated by physiological concentrations of nuclear nicotinamide adenine dinucleotides (NADs). When the nuclear concentration of free NAD and NADH increases, CtBP increases its affinity for viral and cellular repressors and represses transcription. This regulatory mechanism suggests how protein interactions might respond to metabolic balances for the regulation of transcription. Q. Zhang, D. W. Piston, R. H. Goodman, Regulation of corepressor function by nuclear NADH. Science 295, 1895-1897 (2002). [Abstract] [Full Text]
{"title":"A Sense of Cell","authors":"","doi":"10.1126/scisignal.1232002tw103","DOIUrl":"https://doi.org/10.1126/scisignal.1232002tw103","url":null,"abstract":"The transcription factor CtBP associates with transcriptional repressors for the regulation of genes involved in development, cell cycle regulation, and transformation. Zhang et al. show that the corepressor activity of CtBP can be regulated by the redox state of the cell. Mammalian CtBP is regulated by physiological concentrations of nuclear nicotinamide adenine dinucleotides (NADs). When the nuclear concentration of free NAD and NADH increases, CtBP increases its affinity for viral and cellular repressors and represses transcription. This regulatory mechanism suggests how protein interactions might respond to metabolic balances for the regulation of transcription. Q. Zhang, D. W. Piston, R. H. Goodman, Regulation of corepressor function by nuclear NADH. Science 295, 1895-1897 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"72 1","pages":"tw103 - tw103"},"PeriodicalIF":0.0,"publicationDate":"2002-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83241532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-03-12DOI: 10.1126/scisignal.1232002tw105
Dynamic changes in signaling mechanisms may encode specific information critical to cellular regulation. Deciphering these messages requires sophisticated measurements of key signaling molecules in living cells. Teruel and Meyer present a method that allows measurement of calcium-dependent translocation of fluorescently tagged protein kinase Cγ (PKCγ) to the cell membrane in many single, living rat basophilic leukemia cells grown on glass microscope slides. The enzyme showed two distinct modes of response. When calcium was released from internal stores, there was transient movement of PKCγ to the cell surface for only a few seconds. However, signals that caused entry of extracellular calcium caused a persistent translocation of the enzyme to the cell surface that lasted for more than half a minute. Cells showed primarily the former response to low doses of platelet activation factor, and the latter response to larger doses. The results help explain how a common messenger like calcium can control discrete cellular responses. M. N. Teruel, T. Meyer, Parallel single-cell monitoring of receptor-triggered membrane translocation of a calcium-sensing protein module. Science 295, 1910-1912 (2002). [Abstract] [Full Text]
信号机制的动态变化可能编码对细胞调节至关重要的特定信息。破译这些信息需要对活细胞中的关键信号分子进行精密的测量。Teruel和Meyer提出了一种方法，可以测量在玻璃显微镜载玻片上生长的许多单个活大鼠嗜碱性白血病细胞中荧光标记的蛋白激酶Cγ (PKCγ)到细胞膜的钙依赖性易位。酶表现出两种不同的反应模式。当钙从内部储存中释放出来时，PKCγ会短暂地移动到细胞表面，仅持续几秒钟。然而，导致细胞外钙进入的信号导致酶持续易位到细胞表面，持续时间超过半分钟。细胞主要表现为前者对低剂量血小板活化因子的反应，后者对大剂量血小板活化因子的反应。研究结果有助于解释像钙这样的普通信使如何控制离散的细胞反应。M. N. Teruel, T. Meyer，受体触发的钙传感蛋白模块膜易位的平行单细胞监测。科学295,1910-1912(2002)。【摘要】【全文】
{"title":"Dose-Dependent Responses to Calcium","authors":"","doi":"10.1126/scisignal.1232002tw105","DOIUrl":"https://doi.org/10.1126/scisignal.1232002tw105","url":null,"abstract":"Dynamic changes in signaling mechanisms may encode specific information critical to cellular regulation. Deciphering these messages requires sophisticated measurements of key signaling molecules in living cells. Teruel and Meyer present a method that allows measurement of calcium-dependent translocation of fluorescently tagged protein kinase Cγ (PKCγ) to the cell membrane in many single, living rat basophilic leukemia cells grown on glass microscope slides. The enzyme showed two distinct modes of response. When calcium was released from internal stores, there was transient movement of PKCγ to the cell surface for only a few seconds. However, signals that caused entry of extracellular calcium caused a persistent translocation of the enzyme to the cell surface that lasted for more than half a minute. Cells showed primarily the former response to low doses of platelet activation factor, and the latter response to larger doses. The results help explain how a common messenger like calcium can control discrete cellular responses. M. N. Teruel, T. Meyer, Parallel single-cell monitoring of receptor-triggered membrane translocation of a calcium-sensing protein module. Science 295, 1910-1912 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"4 1","pages":"TW105 - tw105"},"PeriodicalIF":0.0,"publicationDate":"2002-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88747017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-02-26DOI: 10.1126/scisignal.1212002tw92
Most conventional cancer drugs gradually lose their effectiveness because tumor cells are genetically unstable and can readily acquire mutations that confer drug resistance. It had been hoped that drug resistance would not be a problem for angiogenesis inhibitors because these drugs target endothelial cells in the tumor vasculature, which are genetically stable. However, Yu et al. found that mice bearing human colorectal tumors deficient in the tumor suppressor protein p53 were less responsive to antiangiogenic therapy than those bearing tumors with normal p53 function. The most likely explanation is that p53 loss confers an improved capacity to grow in low-oxygen conditions on the tumor cells. Because p53 is mutated in most human cancers, these results could have important implications for the design and interpretation of clinical trials testing antiangiogenic drugs. J. L. Yu, J. W. Rak, B. L. Coomber, D. J. Hicklin, R. S. Kerbel, Effect of p53 status on tumor response to antiangiogenic therapy. Science 295, 1526-1528 (2002). [Abstract] [Full Text]
{"title":"Two Steps Forward . . .","authors":"","doi":"10.1126/scisignal.1212002tw92","DOIUrl":"https://doi.org/10.1126/scisignal.1212002tw92","url":null,"abstract":"Most conventional cancer drugs gradually lose their effectiveness because tumor cells are genetically unstable and can readily acquire mutations that confer drug resistance. It had been hoped that drug resistance would not be a problem for angiogenesis inhibitors because these drugs target endothelial cells in the tumor vasculature, which are genetically stable. However, Yu et al. found that mice bearing human colorectal tumors deficient in the tumor suppressor protein p53 were less responsive to antiangiogenic therapy than those bearing tumors with normal p53 function. The most likely explanation is that p53 loss confers an improved capacity to grow in low-oxygen conditions on the tumor cells. Because p53 is mutated in most human cancers, these results could have important implications for the design and interpretation of clinical trials testing antiangiogenic drugs. J. L. Yu, J. W. Rak, B. L. Coomber, D. J. Hicklin, R. S. Kerbel, Effect of p53 status on tumor response to antiangiogenic therapy. Science 295, 1526-1528 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"57 1","pages":"tw92 - tw92"},"PeriodicalIF":0.0,"publicationDate":"2002-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83334663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-02-19DOI: 10.1126/scisignal.1202002tw75
Plant hormones include small peptides, complex chemicals, and steroids known as brassinosteroids. Brassinosteroids regulate, among other aspects, the plant's response to light conditions, its growth habit, and flowering patterns. The signaling pathways controlled by brassinosteroids are likely to be complex and highly branched. Li et al. have cloned and analyzed the BIN2 gene, which encodes a protein that resembles the SHAGGY-type kinases well known for controlling a variety of metabolic pathways in Drosophila, yeast, and mammalian cells. The BIN2 protein product function seemingly early in the brassinosteroid signaling response pathway, but just how closely linked its function is to the initial response of brassinosteroid and its receptor remains unclear. J. Li, K. H. Nam, Regulation of brassinosteroid signaling by a GSK3/SHAGGY-like kinase. Science 295, 1299-1301 (2002). [Abstract] [Full Text]
{"title":"Regulating Plant Steroids","authors":"","doi":"10.1126/scisignal.1202002tw75","DOIUrl":"https://doi.org/10.1126/scisignal.1202002tw75","url":null,"abstract":"Plant hormones include small peptides, complex chemicals, and steroids known as brassinosteroids. Brassinosteroids regulate, among other aspects, the plant's response to light conditions, its growth habit, and flowering patterns. The signaling pathways controlled by brassinosteroids are likely to be complex and highly branched. Li et al. have cloned and analyzed the BIN2 gene, which encodes a protein that resembles the SHAGGY-type kinases well known for controlling a variety of metabolic pathways in Drosophila, yeast, and mammalian cells. The BIN2 protein product function seemingly early in the brassinosteroid signaling response pathway, but just how closely linked its function is to the initial response of brassinosteroid and its receptor remains unclear. J. Li, K. H. Nam, Regulation of brassinosteroid signaling by a GSK3/SHAGGY-like kinase. Science 295, 1299-1301 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"2 1","pages":"tw75 - tw75"},"PeriodicalIF":0.0,"publicationDate":"2002-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90045498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-02-19DOI: 10.1126/scisignal.1202002tw73
Members of the mitogen-activated protein kinase (MAPK) family control a wide range of cellular processes and are regulated as part of a cascade of protein kinases that are activated by sequential phosphorylation. Thus, MAPK kinases phosphorylate MAPKs on specific threonine and tyrosine residues, which leads to activation of the MAPK. Ge et al. (see the Perspective by Johnson) now show that there is another way to activate the so-called stress-activated MAPK known as p38α. They isolated proteins that interacted in a yeast system with human p38α and found TAB1 [transforming growth factor β-activated protein kinase 1 (TAK1)-binding protein 1], a protein previously implicated in activating a different protein kinase, TAK1. TAB1 directly interacted with p38α and thereby enhanced autophosphorylation and activation of the p38α enzyme. Studies of signaling to p38α in cultured cells indicated that some stimuli activate p38α by the conventional kinase cascade, whereas others require the interaction with TAB1 and activation of p38α autophosphorylation. B. Ge, H. Gram, F. Di Padova, B. Huang, L. New, R. J. Ulevitch, Y. Luo, J. Han, MAPKK-independent activation of p38α mediated by TAB1-dependent autophosphorylation of p38α. Science 295, 1291-1294 (2002). [Abstract] [Full Text] G. Johnson, Scaffolding proteins--more than meets the eye. Science 295, 1249-1250 (2002). [Full Text]
丝裂原活化蛋白激酶(MAPK)家族的成员控制着广泛的细胞过程，并作为通过顺序磷酸化激活的蛋白激酶级联的一部分受到调节。因此，MAPK激酶磷酸化特定苏氨酸和酪氨酸残基上的MAPK，从而导致MAPK的激活。Ge等人(参见Johnson的观点)现在表明，有另一种方法可以激活所谓的应力激活MAPK，即p38α。他们分离出酵母系统中与人类p38α相互作用的蛋白，并发现了TAB1[转化生长因子β-活化蛋白激酶1 (TAK1)结合蛋白1]，该蛋白先前与激活另一种蛋白激酶TAK1有关。TAB1直接与p38α相互作用，从而增强p38α酶的自磷酸化和活化。在培养细胞中对p38α信号的研究表明，一些刺激通过常规激酶级联激活p38α，而另一些刺激需要与TAB1相互作用并激活p38α自磷酸化。b . Ge h . g f . Di帕多瓦,黄,l .新的r . j . Ulevitch y罗,j .汉MAPKK-independent p38α介导的激活TAB1-dependent p38α的自身磷酸化。科学通报，2004(2)。【摘要】【全文】G. Johnson, Scaffolding proteins——more than meets the eye。科学295,1249-1250(2002)。(全文)
{"title":"Pull TAB1 to Activate","authors":"","doi":"10.1126/scisignal.1202002tw73","DOIUrl":"https://doi.org/10.1126/scisignal.1202002tw73","url":null,"abstract":"Members of the mitogen-activated protein kinase (MAPK) family control a wide range of cellular processes and are regulated as part of a cascade of protein kinases that are activated by sequential phosphorylation. Thus, MAPK kinases phosphorylate MAPKs on specific threonine and tyrosine residues, which leads to activation of the MAPK. Ge et al. (see the Perspective by Johnson) now show that there is another way to activate the so-called stress-activated MAPK known as p38α. They isolated proteins that interacted in a yeast system with human p38α and found TAB1 [transforming growth factor β-activated protein kinase 1 (TAK1)-binding protein 1], a protein previously implicated in activating a different protein kinase, TAK1. TAB1 directly interacted with p38α and thereby enhanced autophosphorylation and activation of the p38α enzyme. Studies of signaling to p38α in cultured cells indicated that some stimuli activate p38α by the conventional kinase cascade, whereas others require the interaction with TAB1 and activation of p38α autophosphorylation. B. Ge, H. Gram, F. Di Padova, B. Huang, L. New, R. J. Ulevitch, Y. Luo, J. Han, MAPKK-independent activation of p38α mediated by TAB1-dependent autophosphorylation of p38α. Science 295, 1291-1294 (2002). [Abstract] [Full Text] G. Johnson, Scaffolding proteins--more than meets the eye. Science 295, 1249-1250 (2002). [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"21 1","pages":"tw73 - tw73"},"PeriodicalIF":0.0,"publicationDate":"2002-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73343413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-02-12DOI: 10.1126/scisignal.1192002tw70
The cofactor complexes such as ARC (activator-recruited cofactor) and CRSP (cofactor required for Sp1) share several common subunits and mediate interactions between activators and the basal transcription apparatus. Taatjes et al. (see the Perspective by Meisterernst), using biochemical assays and electron microscopy, found that the larger complex, ARC, is composed of two multisubunit complexes, ARC-L and CRSP, and that transcriptional activity is only observed with CRSP. Structural determinations indicate that distinct conformations are induced in the CRSP complex by various activators. Therefore, different activators may allow for different transcriptional readouts based on the specific conformations that form. D. J. Taatjes, A. M. Näär, F. Andel III, E. Nogales, R. Tjian, Structure, function, and activator-induced conformations of the CRSP coactivator. Science 295, 1058-1062 (2002). [Abstract] [Full Text] M. Meisterernst, Mediator meets Morpheus. Science 295, 984-985 (2002). [Full Text]
{"title":"Getting Into Shape","authors":"","doi":"10.1126/scisignal.1192002tw70","DOIUrl":"https://doi.org/10.1126/scisignal.1192002tw70","url":null,"abstract":"The cofactor complexes such as ARC (activator-recruited cofactor) and CRSP (cofactor required for Sp1) share several common subunits and mediate interactions between activators and the basal transcription apparatus. Taatjes et al. (see the Perspective by Meisterernst), using biochemical assays and electron microscopy, found that the larger complex, ARC, is composed of two multisubunit complexes, ARC-L and CRSP, and that transcriptional activity is only observed with CRSP. Structural determinations indicate that distinct conformations are induced in the CRSP complex by various activators. Therefore, different activators may allow for different transcriptional readouts based on the specific conformations that form. D. J. Taatjes, A. M. Näär, F. Andel III, E. Nogales, R. Tjian, Structure, function, and activator-induced conformations of the CRSP coactivator. Science 295, 1058-1062 (2002). [Abstract] [Full Text] M. Meisterernst, Mediator meets Morpheus. Science 295, 984-985 (2002). [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"68 1","pages":"tw70 - tw70"},"PeriodicalIF":0.0,"publicationDate":"2002-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86813532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：