Signal transduction最新文献_第10页

Clinical Add‐on: Multiple sclerosis – clinical picture and therapeutic strategies 临床补充:多发性硬化症-临床图片和治疗策略

Signal transduction Pub Date : 2005-10-01 DOI: 10.1002/SITA.200400056

H. Lins

引用次数: 0

Opioid receptors activate extracellular signal-regulated MAPKs in a receptor tyrosine kinase independent manner 阿片受体以不依赖于受体酪氨酸激酶的方式激活细胞外信号调节的MAPKs

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400040

R. Schulz, A. Wehmeyer

{"title":"Opioid receptors activate extracellular signal-regulated MAPKs in a receptor tyrosine kinase independent manner","authors":"R. Schulz, A. Wehmeyer","doi":"10.1002/SITA.200400040","DOIUrl":"https://doi.org/10.1002/SITA.200400040","url":null,"abstract":"Activation of opioid receptors results in the phosphorylation of two isoforms of extracellular signal-regulated kinases (ERK1/2). While this mechanism is commonly accepted, the path of intracellular signaling leading to the activation of ERK/MAP kinases remained under discussion. A major issue relates to the question whether receptor tyrosine kinases (RTKs), e.g. the epidermal growth factor receptors (EGFRs), mediate opioid receptor-induced phosphorylation of ERKs. For identification of EGFR-related mechanisms a highly selective inhibitor of RTK transactivation, tyrphostin (AG 1478), has been employed during the past, and inhibition of ERK phosphorylation by tyrphostin has been associated with the involvement of RTKs. The present study examines in HEK 293 cells and others the role of RTKs in opioid receptor-evoked activation of ERKs. The experimental techniques employed to control the individual receptor types of the EGFR family were their blockade by tyrphostin, anti-phospho-EGFR-antibodies, anti-EGFR-antibodies, receptor desensitization and EGFR-siRNAs. The results let us conclude that G protein-coupled opioid receptors do not require transactivation of receptors of the EGFR family to phosphorylate ERK/MAP kinases.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"95 9","pages":"184-194"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200400040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950197","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}

引用次数: 1

Methyltransferases in apoptosis and cancer 甲基转移酶在细胞凋亡和癌症中的作用

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400047

R. Schneider-Stock, A. Roessner, O. Ullrich

{"title":"Methyltransferases in apoptosis and cancer","authors":"R. Schneider-Stock, A. Roessner, O. Ullrich","doi":"10.1002/SITA.200400047","DOIUrl":"https://doi.org/10.1002/SITA.200400047","url":null,"abstract":"Chromatin is regarded as the primary cause of epigenetic silencing. In addition DNA methyltransferases and DNA methylation play an important role in the regulation of gene expression. DNA methylation is catalyzed by DNA methyltransferases, which create a site-and tissue-specific DNA methylation pattern during development. The Profiling of these DNA methylation patterns in tumors is believed to provide tools for grading and typing of different cancers. One methylation-maintenance (DNMT1) and two de novo methyltransferases (DNMT3A, DNMT3B) are well characterized. Methyltransferases play their epigenetic concert in crucial positions and intersections of pro- and antiapoptotic pathways: to date, several downstream signal targets have been identified, e. g. p16, DAP-kinase, p14ARF, Apaf1, RARs, caspase 8, and the pro-apoptotic caspase TMS1. These apoptosis-relevant genes are frequently associated with hypermethylation and loss of function in human neoplasia. Transcription factor p53 is one of the major candidates linking alterations in chromatin structure, methyltransferase expression and apoptotic cell death. At present, inactivation of DNMTs using specific inhibitors or antisense strategies is only of limited clinical efficacy. In future, epigenetic processes such as chromatin alteration and DNA methylation will provide promising new targets for therapeutic interventions.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"5 4","pages":"169-176"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200400047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50949958","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}

引用次数: 1

Myostatin and NF-κB Regulate Skeletal Myogenesis Through Distinct Signaling Pathways 肌生长抑制素和NF-κB通过不同的信号通路调控骨骼肌的发生

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400039

Nadine Bakkar, H. Wackerhage, D. Guttridge

{"title":"Myostatin and NF-κB Regulate Skeletal Myogenesis Through Distinct Signaling Pathways","authors":"Nadine Bakkar, H. Wackerhage, D. Guttridge","doi":"10.1002/SITA.200400039","DOIUrl":"https://doi.org/10.1002/SITA.200400039","url":null,"abstract":"Myostatin (Mstn) is a potent negative regulator of skeletal development shown to inhibit myoblast proliferation by impinging on cell cycle and suppressing the synthesis of MyoD. Moreover, Mstn causes muscle wasting and its expression is linked with several conditions of muscle loss, mainly dystrophy and cachexia. NF-κB is a transcription factor that is constitutively active in proliferating myoblasts and also plays a role in cell growth control and skeletal muscle differentiation. NF-κB inhibits myogenesis by promoting myoblast growth and inducing loss of MyoD, and NF-κB activity is required in states of muscle wasting. However, the extracellular factors that regulate NF-κB activity to modulate myogenesis are currently not known. Given the similarities in Mstn and NF-κB activities in muscle cells, we investigated the possibility that Mstn-induced regulation of myogenesis may signal via NF-κB. Using a variety of assays to monitor for NF-κB activity, we found that Mstn signaling does not activate NF-κB in differentiating C2C12 myoblasts, nor is the constitutive activity of NF-κB required for Mstn-mediated inhibition of myogenesis. Likewise, in pre-differentiated myotubes, Mstn signaling induces only a modest activation of NF-κB DNA binding activity. We also investigated whether NF-κB inhibition of myogenesis may occur through the regulation of Mstn. However, activation of NF-κB by TNFα or IL-1β failed to induce Mstn expression. These results thus highlight the distinctive differences by which Mstn and NF-κB signal to regulate myogenesis, a finding which broadens our understanding of how these pathways function in both development and disease.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"26 11","pages":"202-210"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200400039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950188","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}

引用次数: 20

Genome instability as a cause of ageing and cancer: Implications of RecQ helicases 基因组不稳定作为衰老和癌症的原因:RecQ解旋酶的含义

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400052

Camilla Skouboe, Lotte Bjergbaek, A. Andersen

引用次数: 0

Telomeres, cell senescence and human ageing 端粒，细胞衰老和人类衰老

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400049

T. Zglinicki, C. Martin-Ruiz, G. Saretzki

{"title":"Telomeres, cell senescence and human ageing","authors":"T. Zglinicki, C. Martin-Ruiz, G. Saretzki","doi":"10.1002/SITA.200400049","DOIUrl":"https://doi.org/10.1002/SITA.200400049","url":null,"abstract":"Telomeres in most human cell types shorten during DNA replication in vitro because of various factors including the inability of DNA polymerases to fully copy the lagging strand, DNA end processing and random damage, often caused by oxidative stress. Short, uncapped telomeres activate replicative senescence, an irreversible cell cycle arrest and are thus a major cause of cell ageing in vitro. We will review how uncapped telomeres initiate a signalling cascade toward senescence, and why oxidative stress is a major cause of telomere shortening. Telomeres in most human cells shorten during ageing in vivo as well, suggesting two distinct possibilities. (1) Telomere shortening could be among the causes for ageing in vivo: Short telomeres might lead to senescence of (stem) cells in a tissue-specific fashion, and this might contribute to age-related functional attenuation in this tissue and even to systemic effects. Evidence for this is mostly indirect. (2) Telomere length could be a biomarker of ageing and age-related morbidity: Short telomeres might indicate a history of high stress and damage in the individual and could thus act as risk markers for age-related disease residing in a completely different tissue. There is evidence to support this possibility, although it is mostly correlative and is often derived from underpowered studies.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"47 1","pages":"103-114"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200400049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950021","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}

引用次数: 24

Reactive oxygen species (ROS) and aging: Do we need them — can we measure them — should we block them? 活性氧(ROS)和衰老:我们需要它们吗?我们能测量它们吗?我们应该阻止它们吗?

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400053

A. Simm, H. Brömme

引用次数: 34

Retrodifferentiation and reversibility of aging: forever young? 衰老的逆转录分化与可逆性:永远年轻?

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400054

R. Hass

{"title":"Retrodifferentiation and reversibility of aging: forever young?","authors":"R. Hass","doi":"10.1002/SITA.200400054","DOIUrl":"https://doi.org/10.1002/SITA.200400054","url":null,"abstract":"Maturation of stem cells or precursor cells is associated with the acquisition of certain properties finally resulting in specifically functional cell types within the diverse tissues. This maturation process requires distinct steps of differentiation and is accompanied by a constantly increasing process of aging paralleled by a progressively reduced proliferative capacity. The eventually growth arrested and terminally differentiated cells perform their appropriate specific functions associated with developing senescence by STASIS (stress or aberrant signaling-inducing senescence) and/or by replicative senescence. Finally, elimination via apoptosis concludes their life span. However, nature also provides a surprise within this concept of life: Sometimes, differentiation and aging steps are reversible. A biological phenomenon of completely reversible differentiation events has been characterized as retrodifferentiation rather than dedifferentiation. Thus, all morphological and functional properties of retrodifferentiated and previously more undifferentiated cells are indistinguishable. Consequently, reversible differentiation may simultaneously be associated with a reversibility of the aging process and therefore, contributes to longevity and rejuvenation. Tissue renewals or regenerative potential for tissue-specific requirements, if not sufficiently compensated by the appropriate stem cells, may necessitate the generation of undifferentiated precursors by retrodifferentiation followed by a subsequent transdifferentiation process with the consequence of cell type conversion which also includes the risk for tumor development. This interference with the normal biological clock mediated by threshold effects in certain individual cells, raises important questions: What signals trigger retrodifferentiation and what would be the finite life span of cells with a retrodifferentiation capacity?","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"42 11","pages":"93-102"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200400054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950622","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}

引用次数: 8

Reactivation of cardiomyocyte cell cycle: A potential approach for myocardial regeneration 心肌细胞周期的再激活:心肌再生的一种潜在途径

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400050

Nichole M McMullen, Gerard J. Gaspard, K. Pasumarthi

引用次数: 4

A microscale assay for the identification of TGF‐β antagonists based on functional coupling of the heterodimeric TGF‐β receptor to STAT6‐driven promoter activation 基于异二聚体TGF - β受体与STAT6驱动启动子激活功能偶联的TGF - β拮抗剂鉴定微尺度实验

Signal transduction Pub Date : 2005-08-01 DOI: 10.1002/SITA.200400042

Sebastian Krause, K. Friedrich

{"title":"A microscale assay for the identification of TGF‐β antagonists based on functional coupling of the heterodimeric TGF‐β receptor to STAT6‐driven promoter activation","authors":"Sebastian Krause, K. Friedrich","doi":"10.1002/SITA.200400042","DOIUrl":"https://doi.org/10.1002/SITA.200400042","url":null,"abstract":"Inadequate function of Transforming Growth Factor- (TGF-) β is involved in numerous disease states including immune disorders and cancer, rendering this polypeptide and its receptor an attractive target for pharmaceutical interference. We have developed a novel microscale functional test system suited for the investigation of ligand-induced receptor activation and the automatable evaluation of potential agonists and antagonists. Hybrid receptors were constructed from the cytoplasmic domain of the human interleukin-4 (IL-4) receptor α-chain and extracellular domains of a TGF-β type I and type II receptor, respectively. These chimeras were stably introduced into the factor-dependent murine cell line Ba/F3 along with an IL-4-inducible luciferase reporter gene construct, yielding a reporter cell line which responds to productive ligand?receptor interactions by specific luciferase activity in a dose-dependent fashion. A model experiment employing inhibitory peptides demonstrates that the devised reporter cell provides a rational readout for TGF-β activity on target cells and its impairment by specific antagonists.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"54 1","pages":"177-183"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200400042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50949825","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}

引用次数: 6