Journal of signal transduction最新文献

{"title":"Expression and Role of the Intermediate-Conductance Calcium-Activated Potassium Channel KCa3.1 in Glioblastoma.","authors":"Luigi Catacuzzeno,&nbsp;Bernard Fioretti,&nbsp;Fabio Franciolini","doi":"10.1155/2012/421564","DOIUrl":"https://doi.org/10.1155/2012/421564","url":null,"abstract":"<p><p>Glioblastomas are characterized by altered expression of several ion channels that have important consequences in cell functions associated with their aggressiveness, such as cell survival, proliferation, and migration. Data on the altered expression and function of the intermediate-conductance calcium-activated K (KCa3.1) channels in glioblastoma cells have only recently become available. This paper aims to (i) illustrate the main structural, biophysical, pharmacological, and modulatory properties of the KCa3.1 channel, (ii) provide a detailed account of data on the expression of this channel in glioblastoma cells, as compared to normal brain tissue, and (iii) critically discuss its major functional roles. Available data suggest that KCa3.1 channels (i) are highly expressed in glioblastoma cells but only scantly in the normal brain parenchima, (ii) play an important role in the control of glioblastoma cell migration. Altogether, these data suggest KCa3.1 channels as potential candidates for a targeted therapy against this tumor.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"421564"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/421564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30674632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights into the p38γ and p38δ MAPK Pathways.","authors":"Ana Risco,&nbsp;Ana Cuenda","doi":"10.1155/2012/520289","DOIUrl":"https://doi.org/10.1155/2012/520289","url":null,"abstract":"<p><p>The mammalian p38 mitogen-activated protein kinases (MAPKs) family is composed of four members (p38α, p38β, p38γ, and p38δ), which are very similar in amino acid sequence but differ in their expression patterns. This suggests that they may have specific functions in different organs. In the last years most of the effort has been centred on the study of the function of the p38α isoform, which is widely referred to as p38 in the literature. However, the role that other p38 isoforms play in cellular functions and their implication in some of the pathological conditions have not been precisely defined so far. In this paper we highlight recent advances made in defining the functions of the two less studied alternative p38MAPKs, p38γ and p38δ. We describe that these p38MAPKs show similarities to the classical p38α isoform, although they may play central and distinct role in certain physiological and pathological processes.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"520289"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/520289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30330759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-ros crosstalk in the control of cell death and aging.","authors":"Saverio Marchi,&nbsp;Carlotta Giorgi,&nbsp;Jan M Suski,&nbsp;Chiara Agnoletto,&nbsp;Angela Bononi,&nbsp;Massimo Bonora,&nbsp;Elena De Marchi,&nbsp;Sonia Missiroli,&nbsp;Simone Patergnani,&nbsp;Federica Poletti,&nbsp;Alessandro Rimessi,&nbsp;Jerzy Duszynski,&nbsp;Mariusz R Wieckowski,&nbsp;Paolo Pinton","doi":"10.1155/2012/329635","DOIUrl":"https://doi.org/10.1155/2012/329635","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) are highly reactive molecules, mainly generated inside mitochondria that can oxidize DNA, proteins, and lipids. At physiological levels, ROS function as \"redox messengers\" in intracellular signalling and regulation, whereas excess ROS induce cell death by promoting the intrinsic apoptotic pathway. Recent work has pointed to a further role of ROS in activation of autophagy and their importance in the regulation of aging. This review will focus on mitochondria as producers and targets of ROS and will summarize different proteins that modulate the redox state of the cell. Moreover, the involvement of ROS and mitochondria in different molecular pathways controlling lifespan will be reported, pointing out the role of ROS as a \"balance of power,\" directing the cell towards life or death.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"329635"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/329635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30330828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of semaphorins and their receptors in gliomas.","authors":"Janice Wai Sze Law,&nbsp;Alan Yiu Wah Lee","doi":"10.1155/2012/902854","DOIUrl":"https://doi.org/10.1155/2012/902854","url":null,"abstract":"<p><p>Gliomas are the most common tumor in the central nervous system. High-grade glioblastomas are characterized by their high invasiveness and resistance to radiotherapy, leading to high recurrence rate and short median survival despite radical surgical resection. Characterizations of gliomas at molecular level have revealed aberrations of various growth factor receptors, receptor tyrosine kinases, and tumor suppressor genes that lead to deregulation of multiple signaling pathways, thereby contributing to abnormal proliferation, invasion, and resistance to apoptosis in cancer cells. Recently, accumulating evidence points to the emerging role of axon guidance molecules in glioma progression. Notably, many signaling events harnessed by guidance molecules to regulate cell migration and axon navigation during development are also found to be involved in the modulation of deregulated pathways in gliomas. This paper focused on the signalings triggered by the guidance molecule semaphorins and their receptors plexins and neuropilins, and how their crosstalk with oncogenic pathways in gliomas might modulate cancer progression. The emerging role of semaphorins and plexins as tumor suppressors or oncogenes is also discussed.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"902854"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/902854","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30964658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interplay between ROS and Ras GTPases: Physiological and Pathological Implications.","authors":"Elisa Ferro,&nbsp;Luca Goitre,&nbsp;Saverio Francesco Retta,&nbsp;Lorenza Trabalzini","doi":"10.1155/2012/365769","DOIUrl":"https://doi.org/10.1155/2012/365769","url":null,"abstract":"<p><p>The members of the RasGTPase superfamily are involved in various signaling networks responsible for fundamental cellular processes. Their activity is determined by their guanine nucleotide-bound state. Recent evidence indicates that some of these proteins may be regulated by redox agents. Reactive oxygen species (ROSs) and reactive nitrogen species (RNSs) have been historically considered pathological agents which can react with and damage many biological macromolecules including DNA, proteins, and lipids. However, a growing number of reports have suggested that the intracellular production of ROS is tightly regulated and that these redox agents serve as signaling molecules being involved in a variety of cell signaling pathways. Numerous observations have suggested that some Ras GTPases appear to regulate ROS production and that oxidants function as effector molecules for the small GTPases, thus contributing to their overall biological function. Thus, redox agents may act both as upstream regulators and as downstream effectors of Ras GTPases. Here we discuss current understanding concerning mechanisms and physiopathological implications of the interplay between GTPases and redox agents.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"365769"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/365769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30330827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Genetics in Glioma Pathways: The Ever-Increasing Crosstalk between Epigenomic and Genomic Events.","authors":"Ramón Martínez","doi":"10.1155/2012/519807","DOIUrl":"https://doi.org/10.1155/2012/519807","url":null,"abstract":"<p><p>Diffuse gliomas are the most frequent brain tumor in adults. This group of brain neoplasms, ranging from histologically benign to aggressive malignant forms, represents a challenge in modern neurooncology because of the diffuse infiltrative growth pattern and the inherent tendency to relapse as a more malignant tumor. Once the disease achieves the stage of glioblastoma multiforme (GBM), the prognosis of patients is dismal and the median survival time is 15 months. Exhaustive genetic analyses have revealed a variety of deregulated genetic pathways involved in DNA repair, apoptosis, cell migration/adhesion, and cell cycle. Recently, investigation of epigenetic alterations in gliomas has contributed to depict the complexity of the molecular lesions leading to these malignancies. Even though, the efficacy of the state-of-the-art form of chemotherapy in malignant gliomas with temozolomide is based on the methylation-associated silencing of the DNA repair gene MGMT. Nevertheless, the whole scenario including global DNA hypomethylation, aberrant promoter hypermethylation, histone modification, chromatin states, and the role of noncoding RNAs in gliomas has only been partially revealed. We discuss the repercussion of epigenetic alterations underlying deregulated molecular pathways in the pathogenesis and evolution of gliomas and their impact on management of patients.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"519807"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/519807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of HCN Channels on Membrane Excitability in the Nervous System.","authors":"Daisuke Kase,&nbsp;Keiji Imoto","doi":"10.1155/2012/619747","DOIUrl":"https://doi.org/10.1155/2012/619747","url":null,"abstract":"<p><p>Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP(2), and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"619747"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/619747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30869074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Action Potential and After depolarizations Are Not due to Changes in Potassium Currents in NOS3 Knockout Ventricular Myocytes.","authors":"Honglan Wang,&nbsp;Ingrid M Bonilla,&nbsp;Xin Huang,&nbsp;Quanhua He,&nbsp;Mark J Kohr,&nbsp;Cynthia A Carnes,&nbsp;Mark T Ziolo","doi":"10.1155/2012/645721","DOIUrl":"https://doi.org/10.1155/2012/645721","url":null,"abstract":"<p><p>Ventricular myocytes deficient in endothelial nitric oxide synthase (NOS3(-/-)) exhibit prolonged action potential (AP) duration and enhanced spontaneous activity (early and delayed afterdepolarizations) during β-adrenergic (β-AR) stimulation. Studies have shown that nitric oxide is able to regulate various K(+) channels. Our objective was to examine if NOS3(-/-) myocytes had altered K(+) currents. APs, transient outward (I(to)), sustained (I(Ksus)), and inward rectifier (I(K1)) K(+) currents were measured in NOS3(-/-) and wild-type (WT) myocytes. During β-AR stimulation, AP duration (measured as 90% repolarization-APD(90)) was prolonged in NOS3(-/-) compared to WT myocytes. Nevertheless, we did not observe differences in I(to), I(Ksus), or I(K1) between WT and NOS3(-/-) myocytes. Our previous work showed that NOS3(-/-) myocytes had a greater Ca(2+) influx via L-type Ca(2+) channels with β-AR stimulation. Thus, we measured β-AR-stimulated SR Ca(2+) load and found a greater increase in NOS3(-/-) versus WT myocytes. Hence, our data suggest that the prolonged AP in NOS3(-/-) myocytes is not due to changes in I(to), I(Ksus), or I(K1). Furthermore, the increase in spontaneous activity in NOS3(-/-) myocytes may be due to a greater increase in SR Ca(2+) load. This may have important implications for heart failure patients, where arrhythmias are increased and NOS3 expression is decreased.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"645721"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/645721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30898771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal transduction alterations in glioma: implications for diagnosis and therapy.","authors":"Laura Cerchia,&nbsp;Juan-Carlos Martinez Montero,&nbsp;Parisa Monfared","doi":"10.1155/2012/704247","DOIUrl":"https://doi.org/10.1155/2012/704247","url":null,"abstract":"Malignant gliomas are the leading cause of central-nervous-system-tumour-related death, and despite recent advances in surgery, radiotherapy, and chemotherapy, current treatment regimens have a modest survival benefit; the prognosis is even worse in children with brain stem malignant gliomas. \u0000 \u0000Gliomas are divided into four clinical grades on the basis of their histology and prognosis. The most malignant grade 4 astrocytoma, or glioblastoma multiforme (GBM), either arises de novo (usually associated to epidermal growth factor receptor pathway activation and PTEN inactivation leading to PI3K kinase/AKT activation pathway) or progresses from lower grade to higher grade over time (characteristically due to p53 and retinoblastoma pathways inactivation). Due to a combination of its complex phenotype and organ-specific clinical manifestations, efforts to refine GBM treatment with targeted therapies have largely been frustrated. Therefore, the identification and characterization of signal transduction pathways alterations, with a pathogenic role on glioma development and progression, may contribute to the identification of therapeutic targets aimed at a more efficient treatment. \u0000 \u0000The seven tightly organized papers in this special issue give an update of all the latest concepts about the molecular mechanisms of pathogenesis of glioblastoma and new therapeutic opportunities. \u0000 \u0000The molecular characteristics of angiogenesis, a key event for glioma survival, aggressiveness and growth, are addressed by two well-balanced papers. S. Bulnes et al. review angiogenic signaling altered in a rat glioma model and discuss on the selection mechanisms for more aggressive subpopulation with invasive phenotype. They show that glioma stem cells and vascular endothelial cells play a relevant role in the angiogenic process, and referring to molecular pathways, hypoxia inducible factor-1 and vascular endothelial growth factor are the most significant. The papers by V. Cea et al. offers an overview of the most relevant issues about antiangiogenic therapy for glioma, presenting several available drugs that are used or can potentially be utilized for the inhibition of angiogenesis in glioma, focusing on the key mediators of the molecular mechanisms underlying the resistance of glioma to anti-angiogenic therapy. \u0000 \u0000Two interesting and novel papers discuss epigenetic mechanisms producing signal pathways deregulation in gliomas. The paper by R. Alelu-Paz et al. is a nice addition to the current literature about epigenetic changes in human cancer, particularly in gliomas. The emerging role of cancer stem cells in the pathophysiology of cancer is as well discussed. R. Martinez has written a paper describing epigenetic and genetic alterations in gliomas, resulting in deregulation or functional disruption of tumor suppressor and oncogenes. In both papers, the discussion of epigenetic alterations in the pathogenesis and evolution of gliomas clearly indicate their crucial function fo","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"704247"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/704247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31152192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of somatic mutations in the C-terminus of insulin-like growth factor 1 receptor on activity and signaling.","authors":"Barbara P Craddock,&nbsp;W Todd Miller","doi":"10.1155/2012/804801","DOIUrl":"https://doi.org/10.1155/2012/804801","url":null,"abstract":"<p><p>The insulin-like growth factor I receptor (IGF1R) is overexpressed in several forms of human cancer, and it has emerged as an important target for anticancer drug design. Cancer genome sequencing efforts have recently identified three somatic mutations in IGF1R: A1374V, a deletion of S1278 in the C-terminal tail region of the receptor, and M1255I in the C-terminal lobe of the kinase catalytic domain. The possible effects of these mutations on IGF1R activity and biological function have not previously been tested. Here, we tested the effects of the mutations on the in vitro biochemical activity of IGF1R and on major IGF1R signaling pathways in mammalian cells. While the mutations do not affect the intrinsic tyrosine kinase activity of the receptor, we demonstrate that the basal (unstimulated) levels of MAP kinase and Akt activation are increased in the mutants (relative to wild-type IGF1R). We hypothesize that the enhanced signaling potential of these mutants is due to changes in protein-protein interactions between the IGF1R C-terminus and cellular substrates or modulators.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"804801"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/804801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}