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At least 109 records · Page 6Linked to original sources
PubMed1998

Diversity of the endogenous opioid system in development. Novel signal transduction translates multiple extracellular signals into neural cell growth and differentiation.

This review explores the role of individual opioid receptor types and signal transduction pathways on cell growth and differentiation. The findings reviewed herein provide suggestive evidence that while no single opioid receptor or peptide type exclusively regulates growth, depending on the cell type, the activation of all three (mu, delta, or kappa) opioid receptor types can affect maturation in a cell type-dependent manner. Specific developmental responses are determined primarily by how a particular opioid receptor type is coupled to intracellular signaling effectors. Moreover, the coupling of opioid receptors appears to be developmentally regulated, and these protein-protein interactions change during ontogeny. The diversity of opioid receptor types and intracellular effectors may be a mechanism by which individual cells discriminate among different opioid signals, and may permit diverse opioid signals to be translated into a unique developmental logic in distinct neuronal and glial subpopulations.

Animals↗
PubMed2002

SPA1, a component of phytochrome A signal transduction, regulates the light signaling current.

Mutations in a component of phytochrome A (phyA)-specific light signal transduction, SPA1, result in enhanced responsiveness of Arabidopsis seedlings to red and far-red light. Here, we have examined the effects of spa1 mutations on the two known modes of phyA function, the high-irradiance responses (HIRs) to continuous irradiation with far-red light and the very-low-fluence responses (VLFRs) to inductive pulses of light that establish only a small proportion of active phyA. spa1 mutants exhibited an enhanced VLFR under hourly pulses of far-red light for hypocotyl growth inhibition, cotyledon unfolding, anthocyanin accumulation, block of greening in subsequent white light and negative regulation of phyB signaling. We provide evidence that the phenotype of spa1 mutants in red light is also caused by an increase in the VLFR. Taken together, our results indicate that light-induced hypocotyl growth inhibition in spa1 mutants is primarily due to a VLFR. While wild-type seedlings required hourly pulses of far-red light to induce a VLFR, infrequent irradiation with far-red pulses (every 12 h) was sufficient to induce a strong VLFR of hypocotyl elongation in spa1 mutants. This shows that the effect of the VLFR was more persistent in spa1 mutants than in the wild type. We, therefore, propose that SPA1 has an important function in reducing the persistence of phyA signaling. spa1 mutations also enhanced the HIRs of anthocyanin accumulation and of phyA-mediated responsivity amplification towards phyB. Thus, our results suggest that spa1 mutations amplify both the phyA-mediated VLFR and the HIR.

Anthocyanins↗
PubMed2000

Efficient attractor analysis based on self-dependent subsets of elements--an application to signal transduction studies.

External signals are transmitted to the cells through receptors activating signal transduction pathways. These pathways form a complicated interconnected network, which is able to answer to different stimuli. Here we analyze an important pathway for oncogenesis namely RAS/MAPK signal transduction pathway. We show that the interaction of the elements of this pathway induces topological structure in the element set and that the knowledge of the topology simplifies the analysis of the set. With a computer algorithm, we isolate from a large and complex group, smaller, independent, more manageable subsets, and build their hierarchy. Subsets introduction makes easier the search for attractors in discrete dynamical system, it permits the prediction of final states for elements involved in signal transduction pathways.

Algorithms↗
PubMed2006

Sequestration shapes the response of signal transduction cascades.

Many signal transduction cascades are composed of covalent modification cycles such as kinase/phosphatase cycles. In the 1980s Goldbeter and Koshland showed that such cycles can exhibit non-linear input-output relations when the enzymes are saturated by their substrates, which may facilitate signal processing. Recent papers show that this mechanism is unlikely to cause non-linearity in mammalian signal transduction cascades as sequestration of the target due to enzyme concentrations present in these cascades will hamper this mechanism. However, sequestration due to high-affinity enzymes can shape the dynamics and steady-state behaviour of signal transduction cascades in different ways, some of which are discussed in this review.

Kinetics↗
PubMed1998

Role of PP2A in intracellular signal transduction pathways.

Intracellular signal transduction pathways play a crucial role in a variety of cellular processes, such as differentiation, proliferation, or apoptosis, and the reversible phosphorylation of their components is a major regulatory mechanism to control their activities. While much has been learned about the contribution of kinases, the involvement of phosphatases in these events is less clear and has only recently received more investigative attention. The availability of various natural product inhibitors of phosphatases has helped enormously to gain insight into the role that these enzymes exert in various signal transduction processes. This review will focus on serine/threonine protein phosphatase type 2A (PP2A) and will present findings pertaining to its involvement in cellular signal transduction pathways. Since the majority of these studies were done with the use of phosphatase inhibitory compounds, some pros and cons of their application will be presented.

Animals↗
PubMed1997

Platelet activation with combination of ionophore A23187 and a direct protein kinase C activator induces normal secretion in patients with impaired receptor mediated secretion and abnormal signal transduction.

Defects in signal transduction mechanisms may underlie the impaired aggregation and secretion in patients with congenital platelet function defects (CPD). Both protein kinase C (PKC) induced pleckstrin phosphorylation and cytoplasmic Ca2+ mobilization play a major role in secretion. We postulated that combined platelet activation with a cell permeable direct PKC activator 1,2-dioctanoyl-sn-glycerol (DiC8) and ionophore A23187, which possibly bypass the steps involved in the intracellular synthesis of two major mediators (inositol trisphosphate, diacylglycerol), may induce normal dense granule secretion in patients with impaired receptor mediated secretion. We studied eight CPD patients with abnormal aggregation and secretion in response to several different surface receptor-mediated agonists despite the presence of normal dense granule contents. Receptor mediated Ca2+ mobilization and/or pleckstrin phosphorylation were abnormal in seven patients. Platelet activation with a combination of ADP (8 microM) with DiC8 (200 microM) or A23187 (10 microM) improved secretion in four patients. However, platelet activation with a combination of 200 microM DiC8 with 10 microM A23187, or 100 microM DiC8 with 5 microM A23187 induced normal secretion in platelet-rich plasma in all patients. These studies suggest that in such patients with CPD the ultimate process of exocytosis or secretion per se is intact and impaired secretion results from abnormalities in early signal transduction events, possibly upstream of diacylglycerol formation and calcium mobilization. Detailed studies are needed to delineate the specific abnormalities in these heterogenous patients with signal transduction defects.

Adolescent↗
PubMed1989

Antibody valence and induced signal transduction: the role of antibody valence in anti-CD3-induced signal transduction in isolated normal T cells.

This report provides direct evidence that protein kinase C (PKC) is activated in isolated, rigorously accessory cell (AC)-depleted T cells when the T cell antigen recognition complex is stimulated by divalent anti-CD3 monoclonal antibody. Anti-CD3 monoclonal antibody-stimulated PKC activation alone does not, however, directly stimulate T cell proliferation in the absence of AC. A rise in cytosolic calcium is the second signal believed to be of paramount importance in T cell activation. While mitogenic concentrations of some divalent anti-CD3 antibodies do not cause a rise in cytosolic calcium, polyvalent anti-CD3 does evoke increased intracellular Ca2+ in rigorously AC-depleted resting human T cells.

Antibodies, Monoclonal↗
PubMed2004

STCDB: Signal Transduction Classification Database.

The Signal Transduction Classification Database (STCDB) is a database of information relative to the classification of signal transduction. It is based primarily on a proposed classification of signal transduction and it describes each type of characterized signal transduction for which a unique ST number has been provided. This document presents, in its first version, the classification of signal transduction in eukaryotic cells. Approved classifications are available for web browsing at http://www.techfak.uni-bielefeld.de/~ mchen/STCDB.

Animals↗
PubMed2001

A dual role of protein kinase C in insulin signal transduction via adenylyl cyclase signaling system in muscle tissues of vertebrates and invertebrates.

Further decoding of a novel adenylyl cyclase signaling mechanism (ACSM) of the action of insulin and related peptides detected earlier (Pertseva et al. Comp Biochem Physiol B Biochem Mol Biol 1995;112:689-95 and Pertseva et al. Biochem Pharmacol 1996;52:1867-74) was carried out with special attention given to the role of protein kinase C (PKC) in the ACSM. It was shown for the first time that transduction of the insulin signal via the ACSM followed by adenylyl cyclase (AC, EC 4.6.1.1) activation was blocked in the muscle tissues of rat and mollusc Anodonta cygnea in the presence of pertussis toxin, inducing the impairment of G(i)-protein function, wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-K), and calphostin C, a blocker of PKC. The cholera toxin treatment of muscle membranes led to an increase in basal AC activity and a decrease in enzyme insulin reactivity. Phorbol ester and diacylglycerol activation of PKC (acute treatment) induced the inhibition of the insulin AC activating effect. This negative influence was also observed in the case of the AC system activated by biogenic amines. It was first concluded that the ACSM of insulin action involves the following signaling chain: receptor tyrosine kinase => G(i) (betagamma) => PI3-K => PKCzeta (?) => G(s) => AC => adenosine 3',5'-cyclic monophosphate. It was also concluded that the PKC system has a dual role in the ACSM: (1) a regulatory role (PKC sensitive to phorbol esters) that is manifested as a negative feedback modulation of insulin signal transduction via the ACSM; (2) a transductory role, which consists in direct participation of atypical PKC (PKCzeta) in the process of insulin signal transduction via the ACSM.

Adenylyl Cyclases↗
PubMed2000

Signal transduction by a death signal peptide: uncovering the mechanism of bacterial killing by penicillin.

The binding of bactericidal antibiotics like penicillins, cephalosporins, and glycopeptides to their bacterial targets stops bacterial growth but does not directly cause cell death. A second process arising from the bacteria itself is necessary to trigger endogenous suicidal enzymes that dissolve the cell wall during autolysis. The signal and the trigger pathway for this event are completely unknown. Using S. pneumoniae as a model, we demonstrate that signal transduction via the two-component system VncR/S triggers multiple death pathways. We show that the signal sensed by VncR/S is a secreted peptide, Pep27, that initiates the cell death program. These data depict a novel model for the control of bacterial cell death.

Amino Acid Sequence↗
PubMed1996

Interferon signal transduction.

The interferon signal transduction pathway initiates at a cell surface receptor and mediates the activation of target genes in the nucleus. The binding of interferon to a transmembrane receptor stimulates the activation of associated tyrosine kinases of the Janus kinase (JAK) family. Subsequently, latent cytoplasmic transcription factors are activated by tyrosine phosphorylation and function as signal transducers and activators of transcription (STATs). Advances in the field of interferon research have contributed to our understanding of signal transduction induced by many cytokines that also use JAK/STAT signaling pathways to activate early response genes. The specificity of signal activation by distinct cytokines that share these signaling components, and the molecular interaction of the signaling components with each other and their respective cytokine receptors represent major areas of research that are beginning to be elucidated. Signaling molecules other than the JAKs and STATs have also been found to be activated following interferon binding. In addition, the induction of type I interferon stimulated genes by double-stranded RNA in the absence of interferon provides another pathway of specific gene activation.

Animals↗
PubMed2004

Protein tyrosine phosphatases: potential role in beta-cell insulin signal transduction.

Insulin receptor signal transduction plays a critical role in regulating pancreatic beta-cell function, notably the acute first-phase insulin release in response to glucose. The basis for insulin resistance in pancreatic beta-cells is not well understood but may be related to abnormal regulation of tyrosine phosphorylation events, which, in turn, may alter organization of insulin-signaling molecules in space and time. Members of the protein tyrosine phosphatase (PTPase) family are both functionally and structurally diverse; and within the past few years data have emerged from many laboratories that suggest selectivity of the PTPase catalytic domains toward cellular substrates. Of significance, a subset of PTPases has been implicated in the regulation of insulin signaling in a number of insulin-sensitive tissues. Alteration in PTPase expression or activity has been associated with abnormal regulation of tyrosine phosphorylation events and is accompanied by modulation of insulin sensitivity in vivo. Manipulations aimed at reducing expression of physiologically relevant PTPases acting at a step proximal to the insulin receptor are accompanied by normalization of blood glucose levels and improved insulin sensitivity in both normal and diabetic animals. Hence, the development of tissue-specific gene inactivation strategies should facilitate the study of the potential role of PTPases in beta-cell insulin signaling transduction.

Animals↗
PubMed1994

Mutations within the NH2-terminal transmembrane domain of membrane immunoglobulin (Ig) M alters Ig alpha and Ig beta association and signal transduction.

Potentiation of initial signal transduction events through the cross-linking of the B cell antigen receptor complex appears to be dependent upon the association of membrane immunoglobulin (mIg) with Ig alpha and Ig beta. We made two groups of mutations within the COOH terminus of mIgM substituting: 1) the spacer, transmembrane, and cytoplasmic domains and 2) the NH2-terminal 2-8 amino acids within the transmembrane domain (NLWTTAST). We then evaluated the ability of the mutated receptors to associate with Ig alpha and Ig beta and to initiate signal transduction events (Ca2+ mobilization and phosphorylation by tyrosine protein kinases) after cross-linking mIgM receptors. Mutant mIgM receptors containing substitutions of gamma 2b (spacer, transmembrane, and cytoplasmic domains), AA for TT, and AAAAA for TTAST bound Ig alpha and Ig beta and initiated signal transduction events after mIgM receptor cross-linking. However, substitutions of I-A alpha (spacer, transmembrane, and cytoplasmic domains) or TTVVCALGL for NLWTTAST blocked association of Ig alpha and Ig beta and initiation of signal transduction events. Results indicate that residues within the first 8 amino acids of the transmembrane domain other than TTAST are necessary for receptor function and association with Ig alpha and Ig beta.

Amino Acid Sequence↗
PubMed1991

Do second messengers play a role in interferon signal transduction?

The signalling pathway by which the binding of interferons (IFNs, alpha and beta) to their receptor elicits its biological activity, the activation of the transcription of a distinct set of genes called the IFN-stimulated genes (ISG), is far from clear. Debate continues about whether interferon-receptor interaction results directly in gene activation or if second messengers are involved. In this article, we will discuss the evidence that rapid and transient changes in lipid metabolism and the activation of specific isoforms of protein kinase C (PKC) are involved in the initial signalling of interferon activation.

Animals↗
PubMed2006

A variational approach to the stochastic aspects of cellular signal transduction.

Cellular signaling networks have evolved to cope with intrinsic fluctuations, coming from the small numbers of constituents, and the environmental noise. Stochastic chemical kinetics equations govern the way biochemical networks process noisy signals. The essential difficulty associated with the master equation approach to solving the stochastic chemical kinetics problem is the enormous number of ordinary differential equations involved. In this work, we show how to achieve tremendous reduction in the dimensionality of specific reaction cascade dynamics by solving variationally an equivalent quantum field theoretic formulation of stochastic chemical kinetics. The present formulation avoids cumbersome commutator computations in the derivation of evolution equations, making the physical significance of the variational method more transparent. We propose novel time-dependent basis functions which work well over a wide range of rate parameters. We apply the new basis functions to describe stochastic signaling in several enzymatic cascades and compare the results so obtained with those from alternative solution techniques. The variational Ansatz gives probability distributions that agree well with the exact ones, even when fluctuations are large and discreteness and nonlinearity are important. A numerical implementation of our technique is many orders of magnitude more efficient computationally compared with the traditional Monte Carlo simulation algorithms or the Langevin simulations.

Cells↗
PubMed2002

Growth hormone signal transduction.

Multiple signaling pathways mediate the diverse effects of growth hormone (GH) on growth and metabolism. The interaction of GH with GH receptors (GHR) on target cells promotes the association of the cellular tyrosine kinase JAK2 with the GHR, initiating tyrosine phosphorylation of GHR and JAK2, and activation of multiple signaling cascades. GH-stimulated activation of signal transducers and activators of transcription (STATs), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3' kinase (PI3K) cascades have been shown to regulate the transcription of GH-responsive genes. Cross-talk among these signaling cascades in regulating specific genes suggests that GH signaling to the nucleus involves a GH-regulated signaling network.

Animals↗
PubMed1996

[Regulatory mechanisms of receptor-mediated signal transduction].

The signal activation of the target structure, mediated via receptors, could be also the source of some regulatory events. An intensive signaling brings about desensitization, sequestration and down-regulation of receptors, while in the case of absenting signal the sensitization and the up-regulation occur. Such change in the function of one receptor system could influence the function of the other one (we talk about cross-regulation). This review is focused on mechanisms of the homologous regulation (changes in the pathway activated by the appropriate type of receptor) and possible mechanisms of cross-regulation (changes in pathway activated by other type of receptor).

Arrestins↗