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At least 1,603 records · Page 89Linked to original sources
PubMed2005

Specific interaction between Smad1 and CHIP: a surface plasmon resonance study.

The TGF-beta superfamily signaling pathway regulates many important biological processes, including cell growth, differentiation and embryonic pattern formation. Smad1, a member of this signaling pathway that functions downstream of serine/threonine kinase receptors, has ability to interact with carboxyl terminus of Hsc70-interacting protein (CHIP), which is an E3 ubiquitin ligase in other cases. It has been reported that Smurf1, a member of the Hect family E3 ubiquitin ligases, can target Smad1 to 26S proteasome for degradation. In this paper, we studied the interaction of Smad1 and CHIP by combination of surface plasmon resonance and supported monolayer approach. The specific binding of Smad1 to CHIP indicates that the degradation of Smad1 may also be mediated by CHIP, and CHIP may play an essential role in the TGF-beta signaling pathway.

DNA-Binding Proteins↗
PubMed1987

Identification of a signal-transduction pathway shared by haematopoietic growth factors with diverse biological specificity.

The haematopoietic growth factors multi-colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin 2 specifically control the production and proliferation of distinct leucocyte series. Each growth factor acts on a unique surface receptor associated with an appropriate signal-transduction apparatus. In this report we identify a 68 kDa substrate which is phosphorylated after stimulation of different cell types with multi-colony-stimulating factor, granulocyte colony-stimulating factor and interleukin 2. The 68 kDa substrate is also phosphorylated in each cell line stimulated with synthetic diacylglycerol, a direct activator of protein kinase C. Interestingly, granulocyte/macrophage colony-stimulating factor does not induce phosphorylation of the 68 kDa molecule. The 68 kDa molecule that is phosphorylated after stimulation with each ligand yielded similar peptide maps after chymotryptic digestion; furthermore, the substrate was always phosphorylated on threonine residues. Phosphorylation of the same residues in the 68 kDa substrate suggests that activation of protein kinase C is one common signal-transduction event associated with the action of multi-colony-stimulating factor, granulocyte colony-stimulating factor and interleukin 2.

Amino Acids↗
PubMed1990

Molecular cloning, primary structure, and expression of the human platelet/erythroleukemia cell 12-lipoxygenase.

The major pathway of arachidonic acid metabolism in human platelets proceeds via a 12-lipoxygenase enzyme; however, the biological role of the product of this reaction, 12-hydro(pero)xyeicosatetraenoic acid [12-H(P)ETE], is unknown. Using a combination of the polymerase chain reaction and conventional screening procedures, we have isolated cDNA clones encoding the human platelet/human erythroleukemia (HEL) cell 12-lipoxygenase. From the deduced primary structure, human platelet/HEL 12-lipoxygenase would encode a Mr 75,000 protein consisting of 663 amino acids. The cDNA encoding the full-length protein (pCDNA-121x) under the control of the cytomegalovirus promoter was expressed in simian COS-M6 cells. Intact cells and lysed-cell supernatants were able to synthesize 12-H(P)ETE from arachidonic acid, whereas no 12-H(P)ETE synthesis was detected in mock-transfected cells. A single 2.4-kilobase mRNA was detected in erythroleukemia cells but not in several other tissues and cell lines evaluated by Northern blot analysis. Comparison of the human platelet/HEL 12-lipoxygenase sequence with that of porcine leukocyte 12-lipoxygenase and human reticulocyte 15-lipoxygenase revealed 65% amino acid identity to both enzymes. By contrast, the leukocyte 12-lipoxygenase is 86% identical to human reticulocyte 15-lipoxygenase. Sequence data and previously demonstrated immunochemical and biochemical evidence support the existence of distinct 12-lipoxygenase isoforms. The availability of cDNA probes for human platelet/HEL cell 12-lipoxygenase should facilitate elucidation of the biological role of this pathway.

Amino Acid Sequence↗
PubMed1992

Afferent and efferent connections of the bullfrog medial pallium.

Horseradish peroxidase or tritiated proline was unilaterally injected into the medial pallium in bullfrogs in order to determine the sources of afferent projections to the medial pallium and the targets of pallial efferent projections. Some cells in all telencephalic centers, except the corpus striatum and the pars lateralis of the amygdala, project to the ipsilateral medial pallium. The medial pallium receives projections from fewer centers in the contralateral hemisphere, which include the medial septal nucleus, the pars medialis of the amygdala, the bed nucleus of the pallial commissure and the medial pallium. The raphe nucleus and the anterior thalamic nuclei appear to be the only sources of afferents to the medial pallium from outside the telencephalon. Efferents of the medial pallium are far more extensive than reported in earlier studies. The medial pallium projects ipsilaterally to all telencephalic nuclei, with the exception of a large part of the corpus striatum, and contralaterally to the medial septal nucleus, the olfactory tubercle, amygdala, medial pallium and bed nucleus of the pallial commissure. Extensive efferent projections also terminate in preoptic and hypothalamic regions, as well as in most thalamic relay nuclei, the pretectum and, possibly, the optic tectum. Similarities to the medial pallium in other tetrapods and to that in mammals suggest that the medial pallium in anurans is homologous to the subicular and CA fields and, possibly, the dentate gyrus in mammals. However, the extensive projections of the medial pallium to the dorsal thalamus and pretectum in anurans may be primitive features of the medial pallium retained in anurans, or uniquely derived features in anurans.

Afferent Pathways↗
PubMed1997

Biological reactions of peroxynitrite: evidence for an alternative pathway of salicylate hydroxylation.

Salicylate hydroxylation has often been used as an assay of hydroxyl radical production in vivo. We have examined here if hydroxylation of salicylate might also occur by its reaction with peroxynitrite. To test this hypothesis, we exposed salicylate to various concentrations of peroxynitrite, in vitro. We observed the hydroxylation of salicylate at 37 degrees C by peroxynitrite at pH 6, 7 and 7.5, where the primary products had similar retention times on HPLC to 2,3- and 2,5-dihydroxybenzoic acid. The product yields were pH dependent with maximal amounts formed at pH 6. Furthermore, the relative concentration of 2,3- to 2,5-dihydroxybenzoic acid increased with decreasing pH. Nitration of salicylate was also observed and both nitration and hydroxylation reaction products were confirmed independently by mass spectrometry. The spin trap N-t-butyl-alpha-phenylnitrone (PBN), with or without dimethyl sulfoxide (DMSO), was incapable of trapping the peroxynitrite decomposition intermediates. Moreover, free radical adducts of the type PBN/.CH3 and PBN/.OH were susceptible to destruction by peroxynitrite (pH 7, 0.1 M phosphate buffer). These results suggest direct peroxynitrite hydroxylation of salicylate and that the presence of hydroxyl radicals is not a prerequisite for hydroxylation reactions.

Chromatography, High Pressure Liquid↗
PubMed2004

FREX: a query interface for biological processes with hierarchical and recursive structures.

An intelligent system for signal transduction pathways and other higher order functional knowledge is presented. Molecular mechanisms of biological processes are typically represented as diagrams ("pathways") that have a graph-analogical network structure. However, due to the diversity of topics that pathways cover, their constituent biological entities are highly diverse and range from metal ion to protein to biological processes in general. In addition, the kinds of interactions that connect biological entities are likewise diverse. Consequently, current knowledge about pathways is highly heterogeneous both in the sense of the types of constituents and the granularity of descriptions. To cope with this problem, the proposed system adopts a recursive and hierarchical representation model that enables the annotation and query of pathways or sub-pathways of arbitral granularity. By combining the use of this hierarchical structure and biological ontologies, literature-based information regarding biological mechanisms becomes accessible by computer.

Computational Biology↗
PubMed2005

Pathway recognition and augmentation by computational analysis of microarray expression data.

MOTIVATION: We present a system, QPACA (Quantitative Pathway Analysis in Cancer) for analysis of biological data in the context of pathways. QPACA supports data visualization and both fine- and coarse-grained specifications, but, more importantly, addresses the problems of pathway recognition and pathway augmentation. RESULTS: Given a set of genes hypothesized to be part of a pathway or a coordinated process, QPACA is able to reliably distinguish true pathways from non-pathways using microarray expression data. Relying on the observation that only some of the experiments within a dataset are relevant to a specific biochemical pathway, QPACA automates selection of this subset using an optimization procedure. We present data on all human and yeast pathways found in the KEGG pathway database. In 117 out of 191 cases (61%), QPACA was able to correctly identify these positive cases as bona fide pathways with p-values measured using rigorous permutation analysis. Success in recognizing pathways was dependent on pathway size, with the largest quartile of pathways yielding 83% success. In cross-validation tests of pathway membership prediction, QPACA was able to yield enrichments for predicted pathway genes over random genes at rates of 2-fold or better the majority of the time, with rates of 10-fold or better 10-20% of the time. AVAILABILITY: The software is available for academic research use free of charge by email request. SUPPLEMENTARY INFORMATION: Data used in the paper may be downloaded from http://www.jainlab.org/downloads.html

Algorithms↗
PubMed2010

MAP Kinase: SUMO pathway interactions.

The convergence and coordinated cross talk of different signalling pathways forms a regulatory network which determines the biological outcome to environmental cues. The MAPK pathways are one of the important routes by which extracellular signals are transduced into intracellular responses. Through protein phosphorylation mechanisms, they can play a pivotal role in regulating other posttranslational modifications such as protein acetylation and ubiquitination. In addition, protein sumoylation has emerged as an important pathway which also functions through post-translational modification. The SUMO pathway modulates a diverse range of cellular processes including signal transduction, chromosome integrity, and transcription. Interestingly, recent studies have provided links between the SUMO and MAPK signalling pathways which converge to modulate transcription factor activity. This was first demonstrated by the observation that the activation of the ERK pathway caused de-sumoylation of the transcription factor, Elk-1. Furthermore, a growing number of links are now being made between the MAPK pathway and protein sumoylation. Given the nature of protein sumoylation in diverse biological functions, it is not surprising that the effect of MAPK pathways on sumoylation varies between different proteins. Here, we describe protocols that can be used in studying the cross talk between the MAPK and SUMO pathways, particularly at the level of gene regulation.

Amino Acid Sequence↗
PubMed1994

The neu-oncogene: signal transduction pathways, transformation mechanisms and evolving therapies.

A variety of pathways exist to transmit biological signals. One mechanism used for the regulated control of cell growth and differentiation is through the transduction of signals resulting from the binding of soluble polypeptide growth factors to their cognate receptors. The specificity of growth factor action is mediated by the interaction of ligand with cognate receptors which can lead to exquisite control in a tissue- and developmental-specific manner. In addition, individual receptors on the cell surface can form complex assemblies with other receptor/signal transduction molecules that potentially lead to additional levels of signal transmissions. Biological signaling by peptide ligands can be mediated through the enzymatic activation of the receptor resulting in the triggering of a defined biochemical pathway. Ultimately, a mitogenic or differentiation signal is delivered to the nucleus, completing the biological action of the growth factor. The biochemical mechanisms of signal transduction by the p185 neu/c-erbB-2 growth factor receptor and the subsequent physiological responses are the topics of this review. Study of the p185 growth factor receptor has helped to illustrate the functional role of receptor homo- (and hetero-) dimerization in enzyme activation and, in malignant cells, the detrimental results of structural mutations or aberrant gene expression which may effect this dimerization. The ability of one type of growth factor receptor to affect the activity of another (as illustrated by the p185/epidermal growth factor receptor heterodimeric complex) is likely to be a common regulatory feature of growth factor receptor action. The nomenclature to be used in this review will refer to the oncogenic mutated form of the rat protein as 'p185neu', the proto-oncogenic rat protein as 'p185c-neu' and the human form as 'p185c-erbB-2'. The term 'p185' will be used to refer to any type of protein, regardless of the source.

Animals↗
PubMed2000

Jak-Stat signal transduction pathway through the eyes of cytokine class II receptor complexes.

Cells of the immune system communicate with each other to initiate, establish and maintain immune responses. The communication occurs through cell-to-cell contact or through a variety of intercellular mediators that include cytokines, chemokines, growth factors and hormones. In the case of cytokines, the signal is transmitted from the outside to the inside of a cell through cell surface receptors specific for each cytokine. At this step the signal is also decoded and amplified: ligand binding causes recruitment and/or activation of numerous cytoplasmic proteins. One cytokine can activate a number of signal transduction pathways leading to regulation of a wide array of biological activities. One of these pathways, the Jak-Stat pathway, is briefly reviewed here with respect to the class II cytokine receptors. Signal transduction through receptors for interferons Type I (IFN-alpha, IFN-beta, IFN-omega) and Type II (IFN-gamma), and interleukin 10 (IL-10) is described in detail. In addition, a complex between tissue factor (TF) and coagulation factor VIIa, and two new receptors related to the class II cytokine receptor family are discussed. Oncogene (2000).

Amino Acid Sequence↗
PubMed2003

Oncogenes in thyroid cancer.

There have been significant advances in our understanding of carcinogenesis at the molecular level over the last 25 years. Oncogenes are of major interest as part of our search for knowledge surrounding the aetiology of cancer. There are several oncogenes associated with thyroid cancer. Detailed investigation of the nature and function of these tumour genes has provided important insights into both the tumour biology and the complex biochemical pathways of normal cellular functioning. Our knowledge of oncogene biology offers the hope of better diagnostic, therapeutic and prognostic modalities in our fight against this and other common cancers. Development of specific thyroid tumour markers and gene therapy is now a realistic prospect to supplement our present armamentarium of surgery and radiotherapy. This review aims to outline the pertinent information gained so far from studies of these oncogenes and provides both clinical relevance and fuel for further interest amongst the ENT thyroid community in this exciting area of research.

Carcinoma, Medullary↗
PubMed1999

Vascular endothelial growth factor in reproductive biology.

The critical role of angiogenesis in embryology and tumor biology has been recognized for more than 20 years. However, the fact that neovascularization is essential to processes in mammalian female reproduction has only recently been appreciated widely. In this review we focus on a single angiogenic growth factor, vascular endothelial growth factor. As scientists have discovered in many aspects of cell biology, multiple and redundant signaling pathways have evolved in nature, presumably to protect essential biological functions from inactivating diseases or mutations. Despite this redundancy, some factors are of hierarchical importance. Vascular endothelial growth factor appears to be such a factor in the regulation of angiogenesis.

Endometrium↗
PubMed1998

Genetics and physiology of aflatoxin biosynthesis.

Aflatoxins are the most thoroughly studied mycotoxins. Elegant early research on the biosynthetic scheme of the pathway has allowed a molecular characterization of aflatoxin biosynthesis and its regulation. Genetic studies on aflatoxin biosynthesis in Aspergillus flavus and A. parasiticus, and sterigmatocystin biosynthesis in A. nidulans, led to the cloning of 17 genes responsible for 12 enzymatic conversions in the AF/ST pathways. Pathway-specific regulation is by a Zn(II)2Cys6 DNA-binding protein that regulates the transcription of all pathway genes. Less is known about the global factors that regulate aflatoxin biosynthesis, but there is a clear link between development and aflatoxin biosynthesis. There is also a large body of information on physiological factors involved in aflatoxin biosynthesis, but it has been difficult to understand their role in the regulation of this pathway. This chapter discusses current knowledge on the molecular biology and genetics of the pathway, and provides a summary of the physiological factors known to influence aflatoxin formation.

Journal Article↗
PubMed1998

The pathogenesis of Alzheimer's disease.

Despite consensus on clinical and neuropathologic definitions of Alzheimer's disease, limited information is available on its causes and pathogenesis. Current data suggest interactions among the various possible biological and environmental influences that result in a common pathway leading to the disease. Biological influences include genetic mutations causing the disease phenotype and polymorphisms contributing to disease risk. Alterations in immune or inflammatory responses may also represent biological influences. Various environmental influences that may interact with endogenous biological factors include education, traumatic injury, oxidative stress, drugs, and hormone replacement. The author describes some recent findings that suggest possible pathogenic mechanisms, which may eventually have important treatment implications.

Alzheimer Disease↗
PubMed1999

Negative regulation of the JAK/STAT pathway.

Cytokines induce a variety of biological responses by binding to specific cell surface receptors and activating cytoplasmic signal transduction pathways, such as the JAK/STAT pathway. Although these responses are generally transient, few molecules have been characterised that switch the signal off. Several different steps of the signal transduction pathway appear to be targeted by negative regulators, including the receptor/ligand complex, JAK kinases, and STAT transcription factors. Negative regulation is achieved by dephosphorylation of signalling intermediates by protein tyrosine phosphatases such as SHP-1, and by proteolytic degradation. Recent studies have identified two new families of negative regulatory molecules, SOCS and PIAS, which function in novel ways to suppress signal transduction pathways. The duration and intensity of a cell's response to cytokine therefore appear to be determined by the net effect of several regulatory mechanisms.

Animals↗