Regulation between nitric oxide and MAPK signal transduction in mammals

Nitric oxide (NO) is an important biological messenger in the regulation of tissue homeostasis. It exhibits a wide range of effects during physiological and pathophysiological processes. Typical beneficial properties of NO include the regulation of vascular tone,the protection of cells against apoptosis, the modulation of immune responses, and the killing of microbial pathogens. On the other hand,NO may cause severe vasodilation and myocardial depression during bacterial sepsis or act as a cytotoxic and tissue-damaging molecule in autoimmune diseases. Mitogen-activated protein kinase (MAPK) is a family of serine/threonine protein kinases that are widely distributed in mammalian cells. MAPK cascade plays pivotal roles in gene expression, cell proliferation, differentiation, neuronal survival and programmed cell death under a variety of experimental conditions. MAPKs transduce the signal for the cellular response to extracellular stresses or stimuli. The relation between them, however, has never been reviewed. Based on our researches and other reports in the field, we review their reciprocal regulatory functions.     

LDL-receptor-related proteins in Wnt signal transduction

The Wnt family of secreted signalling molecules are essential in embryo development and tumour formation. The Frizzled (Fz) family of serpentine receptors function as Wnt receptors, but how Fz proteins transduce signalling is not understood. In Drosophila, arrow phenocopies the wingless (DWnt-1) phenotype, and encodes a transmembrane protein that is homologous to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12-15). Here we report that LRP6 functions as a co-receptor for Wnt signal transduction. In Xenopus embryos, LRP6 activated Wnt-Fz signalling, and induced Wnt responsive genes, dorsal axis duplication and neural crest formation. An LRP6 mutant lacking the carboxyl intracellular domain blocked signalling by Wnt or Wnt-Fz, but not by Dishevelled or beta-catenin, and inhibited neural crest development. The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex.     

Inositol trisphosphate, a novel second messenger in cellular signal transduction

There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.     

Links between annual, Milankovitch and continuum temperature variability

Climate variability exists at all timescales-and climatic processes are intimately coupled, so that understanding variability at any one timescale requires some understanding of the whole. Records of the Earth's surface temperature illustrate this interdependence, having a continuum of variability following a power-law scaling. But although specific modes of interannual variability are relatively well understood, the general controls on continuum variability are uncertain and usually described as purely stochastic processes. Here we show that power-law relationships of surface temperature variability scale with annual and Milankovitch-period (23,000- and 41,000-year) cycles. The annual cycle corresponds to scaling at monthly to decadal periods, while millennial and longer periods are tied to the Milankovitch cycles. Thus the annual, Milankovitch and continuum temperature variability together represent the response to deterministic insolation forcing. The identification of a deterministic control on the continuum provides insight into the mechanisms governing interannual and longer-period climate variability.     

Cell cycle and cell signal transduction in marine phytoplankton

tAs unicellular phytoplankton, the growth of a marine phytoplankton population results directly from the completion of a cell cycle, therefore, cell-environment communication is an important way which involves signal transduction pathways to regulate cell cycle progression and contribute to growth, metabolism and primary production and respond to their surrounding environment in marine phytoplankton. Cyclin-CDK and CaM/Ca²⁺ are essentially key regulators in control of cell cycle and signal transduction pathway, which has important values on both basic research and applied biotechnology. This paper reviews progress made in this research field, which involves the identification and characterization of cyclins and cell signal transduction system, cell cycle-control mechanisms in marine phytoplankton cells, cell cycle proteins as a marker of a terminal event to estimate the growth rate of phytoplankton at the species level, cell cycle-dependent toxin production of toxic algae and cell cycle progression regulated by environmental factors.     

蓝藻真核型蛋白质激酶与信号传导

对最近10年在蓝藻中找到大量编码Ser／Thr基因的研究结果进行了综述,并对这些蛋白质激酶在信号传导中的作用模式做了讨论．     

Links between erosion, runoff variability and seismicity in the Taiwan orogen

The erosion of mountain belts controls their topographic and structural evolution and is the main source of sediment delivered to the oceans. Mountain erosion rates have been estimated from current relief and precipitation, but a more complete evaluation of the controls on erosion rates requires detailed measurements across a range of timescales. Here we report erosion rates in the Taiwan mountains estimated from modern river sediment loads, Holocene river incision and thermochronometry on a million-year scale. Estimated erosion rates within the actively deforming mountains are high (3-6 mm yr(-1)) on all timescales, but the pattern of erosion has changed over time in response to the migration of localized tectonic deformation. Modern, decadal-scale erosion rates correlate with historical seismicity and storm-driven runoff variability. The highest erosion rates are found where rapid deformation, high storm frequency and weak substrates coincide, despite low topographic relief.     

Isolation of 3,4-didehydroretinoic acid, a novel morphogenetic signal in the chick wing bud

There is increasing evidence that retinoic acid is a morphogen involved in vertebrate development. This evidence comes in part from studies of the chick wing bud, in which local application of all-trans-retinoic acid results in a duplication of the digit pattern along the anteroposterior axis. Retinoic acid may be only one of several morphogenetic signalling compounds required for limb pattern formation. To identify novel morphogenetically active compounds, fractionated extracts of whole chick embryos were tested for their ability to induce digit pattern duplications. We describe here the isolation of a new activity present in the limb bud, which we have identified as all-trans-3,4-didehydroretinoic acid. The 3,4-didehydroretinoic acid is generated in situ from retinol through a 3,4-didehydroretinol intermediate. We show that 3,4-didehydroretinoic acid and retinoic acid are equipotent in evoking digit duplications. These findings suggest that there are at least two endogenous retinoids with morphogenetic properties in the chick limb.     

Protein methylation in behavioural control mechanisms and in signal transduction.

In both prokaryotes and eukaryotes methyl groups can be added to and removed from the carboxyl groups of proteins. Recent work has revealed that these reactions have a role in several behavioural phenomena. The nature of this role has been uncovered in one case--that of bacterial chemotaxis.     

植物抗病性的分子机制和信号传导

植物抗病性的分子机制一直是植物病理学关注的焦点.近年来,国内外不少学者和实验室正在大量分离和培养与抗病有关的突变体,并且寻找和研究与抗病有关的基因和抗病机制.研究表明,在病原物与植物的相互作用、病原信号的传导和抗病性激发的过程中存在着一系列的调节因子和基因,并形成复杂的调控网络.综述了近年来国内外植物抗病性的分子研究进展,阐述了植物抗病性分子机制和信号传导.     

Cytokinin signal transduction： Known simplicity and unknown complexity

Cytokinin plays a critical role in plant growth and development by regulating cell divisions and cell differentiation. Recent studies suggest that cytokinin signaling is presumably mediated by a two-component system analogous to those found in bacteria and fungi, which transduces an external signal via a phosphorelay from the plasma membrane-anchored receptors to downstream effectors and regulators. Moreover, cytokinin signaling is highly interactive with other pathways, and many components of the pathway appear to be functionally redundant. Proper address of these questions will be crucial for our further understanding on this important network.     

Oscillation and noise determine signal transduction in shark multimodal sensory cells

Oscillating membrane potentials that generate rhythmic impulse patterns are considered to be of particular significance for neuronal information processing. In contrast, noise is usually seen as a disturbance which limits the accuracy of information transfer. We show here, however, that noise in combination with intrinsic oscillations can provide neurons with particular encoding properties, a discovery we made when recording from single electro-sensory afferents of a fish. The temporal sequence of the impulse trains indicates oscillations that operate near the spike-triggering threshold. The oscillation frequency determines the basic rhythm of impulse generation, but whether or not an impulse is actually triggered essentially depends on superimposed noise. The probability of impulse generation can be altered considerably by minor modifications of oscillation baseline and amplitude, which may underlie the exquisite sensitivity of these receptors to thermal and electrical stimuli. Additionally, thermal, but not electrical, stimuli alter the oscillation frequency, allowing dual sensory messages to be conveyed in a single spike train. These findings demonstrate novel properties of sensory transduction which may be relevant for neuronal signalling in general.     

Local inhibition and long-range enhancement of Dpp signal transduction by Sog

Extracellular gradients of signalling molecules can specify different thresholds of gene activity in development. A gradient of Decapentaplegic (Dpp) activity subdivides the dorsal ectoderm of the Drosophila embryo into amnioserosa and dorsal epidermis. The proteins Short gastrulation (Sog) and Tolloid (Tld) are required to shape this gradient. Sog has been proposed to form an inhibitory complex with either Dpp or the related ligand Screw, and is subsequently processed by the protease Tld. Paradoxically, Sog appears to be required for amnioserosa formation, which is specified by peak Dpp signalling activity. Here we show that the misexpression of sog using the even-skipped stripe-2 enhancer redistributes Dpp signalling in a mutant background in which dpp is expressed throughout the embryo. Dpp activity is diminished near the Sog stripe and peak Dpp signalling is detected far from this stripe. However, a tethered form of Sog suppresses local Dpp activity without augmenting Dpp activity at a distance, indicating that diffusion of Sog may be required for enhanced Dpp activity and consequent amnioserosa formation. The long-distance stimulation of Dpp activity by Sog requires Tld, whereas Sog-mediated inhibition of Dpp does not. The heterologous Dpp inhibitor Noggin inhibits Dpp signalling but fails to augment Dpp activity. These results suggest an unusual strategy for generating a gradient threshold of growth-factor activity, whereby Sog and its protease specify peak Dpp signalling far from a localized source of Sog.     

Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases.

Rhodopsin kinase and beta-adrenergic receptor kinase (beta ARK) are related members of a serine/threonine kinase family that specifically initiate deactivation of G-protein-coupled receptors. After stimulus-mediated receptor activation, these cytoplasmic kinases translocate to the plasma membrane. Here we show that the molecular basis for this event involves a class of unsaturated lipids called isoprenoids. Covalent modification in vivo of rhodopsin kinase by a 15-C (farnesyl) isoprenoid enables the kinase to anchor to photon-activated rhodopsin. Mutations that alter or eliminate the isoprenoid, fully disable light-specific Rhodopsin kinase translocation. Other receptor kinases (such as beta ARK), which lack an intrinsic lipid, are activated on exposure to brain beta gamma subunits of the signal-transducing G proteins, the gamma subunit of which bears a 20-C (geranylgeranyl) isoprenoid. Using chimaeric beta ARKs that undergo isoprenylation in vitro, we demonstrate that membrane association and activation of these kinases can occur in the absence of beta gamma. These results indicate that rhodopsin kinase (by means of an integral isoprenoid) and beta ARK (through its association with beta gamma) both rely on the function of isoprenyl moieties for their translocation and activity, illustrating distinct, though related, modes of biological regulation of receptor function.