Genomes and Genes
Experts and Doctors on signal transduction in Dundee, KwaZulu Natal, South Africa
Locale: Dundee, KwaZulu Natal, South Africa
Topic: signal transduction
- Bown J, Andrews P, Deeni Y, Goltsov A, Idowu M, Polack F, et al. Engineering simulations for cancer systems biology. Curr Drug Targets. 2012;13:1560-74 pubmed
- Cohen P. The regulation of protein function by multisite phosphorylation--a 25 year update. Trends Biochem Sci. 2000;25:596-601 pubmed..Multisite phosphorylation can enable several such effects to operate in the same protein. It can also determine the extent and duration of a response and is the key to signal integration. ..
- Goltsov A, Faratian D, Langdon S, Bown J, Goryanin I, Harrison D. Compensatory effects in the PI3K/PTEN/AKT signaling network following receptor tyrosine kinase inhibition. Cell Signal. 2011;23:407-16 pubmed publisher..We discuss the application of the results to the challenges of hypersensitivity of the signaling network to RTK signals, suppression of drug resistance, and efficacy of drug combinations in anticancer therapy. ..
- Coates P, Robinson J, Lorimore S, Wright E. Ongoing activation of p53 pathway responses is a long-term consequence of radiation exposure in vivo and associates with altered macrophage activities. J Pathol. 2008;214:610-6 pubmed publisher..The data implicate persistent activation of inflammatory-type responses in irradiated tissues as a contributory bystander mechanism for causing delayed DNA damage. ..
- Liu R, Iadevaia V, Averous J, Taylor P, Zhang Z, Proud C. Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors. Nucleic Acids Res. 2014;42:5083-96 pubmed publisher..Therefore, our data demonstrate that disrupting rRNA production activates mTORC1 signalling to enhance the efficiency of the translational machinery, likely to help compensate for impaired ribosome production. ..
- Proud C. Role of mTOR signalling in the control of translation initiation and elongation by nutrients. Curr Top Microbiol Immunol. 2004;279:215-44 pubmed
- McGregor G, Irving A, Harvey J. Canonical JAK-STAT signaling is pivotal for long-term depression at adult hippocampal temporoammonic-CA1 synapses. FASEB J. 2017;31:3449-3466 pubmed publisher..McGregor, G., Irving, A. J., Harvey, J. Canonical JAK-STAT signaling is pivotal for long-term depression at adult hippocampal temporoammonic-CA1 synapses. ..
- An S, Chin K, Febrer M, McCarthy Y, Yang J, Liu C, et al. A cyclic GMP-dependent signalling pathway regulates bacterial phytopathogenesis. EMBO J. 2013;32:2430-8 pubmed publisher..These findings describe a regulatory pathway in which cyclic GMP regulates virulence and biofilm formation through interaction with a novel effector that directly links cyclic GMP and cyclic di-GMP signalling. ..
- Atrih A, Mudaliar M, Zakikhani P, Lamont D, Huang J, Bray S, et al. Quantitative proteomics in resected renal cancer tissue for biomarker discovery and profiling. Br J Cancer. 2014;110:1622-33 pubmed publisher..Two proteins validated in this study are the focus of on-going research in a large cohort of patients. ..
- Rojas Fernandez A, PlechanovovÃ¡ A, Hattersley N, Jaffray E, Tatham M, Hay R. SUMO chain-induced dimerization activates RNF4. Mol Cell. 2014;53:880-92 pubmed publisher..Thus the ubiquitin E3 ligase activity of RNF4 is directly linked to the availability of its polySUMO substrates. ..
- Stevense M, Muramoto T, Muller I, Chubb J. Digital nature of the immediate-early transcriptional response. Development. 2010;137:579-84 pubmed publisher..Biased digital responses may be necessary for certain forms of developmental specification. Limiting bias in responsiveness is required to reduce noise in positional signalling. ..
- Plummer S, Sharpe R, Hallmark N, Mahood I, Elcombe C. Time-dependent and compartment-specific effects of in utero exposure to Di(n-butyl) phthalate on gene/protein expression in the fetal rat testis as revealed by transcription profiling and laser capture microdissection. Toxicol Sci. 2007;97:520-32 pubmed..The observed gene expression changes, and their compartmentalization, suggest a possible role for peroxisome proliferator-mediated alteration of cofactor availability as a mechanism underlying DBP-induced Leydig cell dysfunction. ..
- Tiecke E, Turner R, Sanz Ezquerro J, Warner A, Tickle C. Manipulations of PKA in chick limb development reveal roles in digit patterning including a positive role in Sonic Hedgehog signaling. Dev Biol. 2007;305:312-24 pubmed..PKA levels in the limb bud are high posteriorly and low anteriorly, suggesting that PKA activity may influence the outcome of Shh signaling in normal development. ..
- Valentine T, Roberts I, Oparka K. Inhibition of tobacco mosaic virus replication in lateral roots is dependent on an activated meristem-derived signal. Protoplasma. 2002;219:184-96 pubmed..The data suggest that viral inhibition in lateral roots occurs by a gene-silencing-like mechanism that is dependent on the activation of a lateral-root meristem. ..
- Tiecke E, Bangs F, Blaschke R, Farrell E, Rappold G, Tickle C. Expression of the short stature homeobox gene Shox is restricted by proximal and distal signals in chick limb buds and affects the length of skeletal elements. Dev Biol. 2006;298:585-96 pubmed..These results fit well with the proposed role of Shox in cartilage and bone differentiation and suggest chick embryos as a useful model to study further the role of Shox in limb development. ..
- Davey M, James J, Paton I, Burt D, Tickle C. Analysis of talpid3 and wild-type chicken embryos reveals roles for Hedgehog signalling in development of the limb bud vasculature. Dev Biol. 2007;301:155-65 pubmed..Thus Hedgehog signalling has a pivotal role in the cascade of angiogenic events in a growing embryonic organ which is similar to that proposed in tumours. ..
- Turban S, Beardmore V, Carr J, Sakamoto K, Hajduch E, Arthur J, et al. Insulin-stimulated glucose uptake does not require p38 mitogen-activated protein kinase in adipose tissue or skeletal muscle. Diabetes. 2005;54:3161-8 pubmed
- Araki T, Tsujioka M, Abe T, Fukuzawa M, Meima M, Schaap P, et al. A STAT-regulated, stress-induced signalling pathway in Dictyostelium. J Cell Sci. 2003;116:2907-15 pubmed..These data show that Dd-STATc functions as a transcriptional activator in a stress-response pathway and the pharmacological evidence, at least, is consistent with cGMP acting as a second messenger. ..
- Yamada Y, Núñez Corcuera B, Williams J. DIF-1 regulates Dictyostelium basal disc differentiation by inducing the nuclear accumulation of a bZIP transcription factor. Dev Biol. 2011;354:77-86 pubmed publisher..These results suggest that the differentiation of pstB cells is caused by a high perceived level of DIF-1 signalling, leading to nuclear localization of DimB and direct activation of cell type-specific gene expression. ..
- Dickinson R, Eblaghie M, Keyse S, Morriss Kay G. Expression of the ERK-specific MAP kinase phosphatase PYST1/MKP3 in mouse embryos during morphogenesis and early organogenesis. Mech Dev. 2002;113:193-6 pubmed..Most of these have been characterised as sites of FGF/FGFR signalling. ..
- Hunter M, Treharne K, Winter A, Cassidy D, Land S, Mehta A. Expression of wild-type CFTR suppresses NF-kappaB-driven inflammatory signalling. PLoS ONE. 2010;5:e11598 pubmed publisher..Our data therefore concur with in vivo and in vitro data from Vij and colleagues which highlights CFTR as a suppressor of basal inflammation acting through NF-kappaB, a central hub in inflammatory signalling. ..
- Nicol S, Bray S, Black H, Lorimore S, Wright E, Lane D, et al. The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage. Oncogene. 2013;32:3461-9 pubmed publisher..These data highlight a novel function of p68 as a modulator of the decision between p53-mediated growth arrest and apoptosis in vitro and in vivo. ..
- ..The chapter closes with a scenario for the evolution of Dictyostelid multicellularity from an Amoebozoan stress response. ..
- Meunier I, Lenaers G, Bocquet B, Baudoin C, Piro Megy C, Cubizolle A, et al. A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium. Hum Mol Genet. 2016;25:916-26 pubmed publisher..These findings shed new lights on Bruch's membrane/RPE pathophysiology and will open studies of this signaling pathway in diseases with RPE and Bruch's membrane alterations, such as age-related macular degeneration. ..
- Stevenson L, Sparks A, Allende Vega N, Xirodimas D, Lane D, Saville M. The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2. EMBO J. 2007;26:976-86 pubmed..Our data identify the deubiquitinating enzyme USP2a as a novel regulator of the p53 pathway that acts through its ability to selectively target Mdm2. ..
- An S, Febrer M, McCarthy Y, Tang D, Clissold L, Kaithakottil G, et al. High-resolution transcriptional analysis of the regulatory influence of cell-to-cell signalling reveals novel genes that contribute to Xanthomonas phytopathogenesis. Mol Microbiol. 2013;88:1058-69 pubmed publisher..Importantly, functional analysis revealed over 160 new virulence factors within the group of Rpf-regulated genes...
- McLeod L, Proud C. ATP depletion increases phosphorylation of elongation factor eEF2 in adult cardiomyocytes independently of inhibition of mTOR signalling. FEBS Lett. 2002;531:448-52 pubmed..Only at later times is an effect on mTOR signalling observed. These data suggest that energy depletion leads to inhibition of protein synthesis through phosphorylation of eEF2 independently of inhibition of mTOR signalling. ..
- Zhao H, Hyde R, Hundal H. Signalling mechanisms underlying the rapid and additive stimulation of NKCC activity by insulin and hypertonicity in rat L6 skeletal muscle cells. J Physiol. 2004;560:123-36 pubmed..Furthermore, activation of NKCC in response to hyperosmotic-induced cell shrinkage represents a critical component of the RVI mechanism that allows L6 muscle cells to volume regulate. ..
- Hundal H, Taylor P. Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab. 2009;296:E603-13 pubmed publisher..We hypothesize (by extrapolation from knowledge of the yeast Ssy1 transceptor) that, at least for SNAT2, the transceptor discriminates between extracellular and intracellular amino acid stimuli when evoking a signal. ..
- Dieterle A, Böhler P, Keppeler H, Alers S, Berleth N, Driesen S, et al. PDK1 controls upstream PI3K expression and PIP3 generation. Oncogene. 2014;33:3043-53 pubmed publisher..Our study suggests that the efficiency of therapies targeting the aberrantly activated PI3K/PDK1/Akt pathway might be increased by the parallel blockade of feedback circuits. ..
- Ritchie A, van Es S, Fouquet C, Schaap P. From drought sensing to developmental control: evolution of cyclic AMP signaling in social amoebas. Mol Biol Evol. 2008;25:2109-18 pubmed publisher..We propose that high osmolality signals drought in soil amoebas and that developmental cAMP signaling in the Dictyostelia has evolved from this stress response. ..
- Schaap P. Cyclic di-nucleotide signaling enters the eukaryote domain. IUBMB Life. 2013;65:897-903 pubmed publisher..Compared to the limited number of conserved protein domains that detect the second messengers cAMP and cGMP, the domains that detect the c-di-NMPs are surprisingly varied. ..
- Richardson C, Rafiqi F, Karlsson H, Moleleki N, Vandewalle A, Campbell D, et al. Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1. J Cell Sci. 2008;121:675-84 pubmed publisher..They also suggest a mechanism by which increased WNK1 overexpression could lead to hypertension and that inhibitors of SPAK/OSR1 might be of use in reducing blood pressure by suppressing phosphorylation and hence activity of NCC. ..
- Dormann D, Weijer C. Imaging of cell migration. EMBO J. 2006;25:3480-93 pubmed
- Bruce D, MacArtney T, Yong W, Shou W, Sapkota G. Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-? pathway. Cell Signal. 2012;24:1999-2006 pubmed publisher..We propose that PP5 regulates the TGF? pathway in MEFs by regulating the expression of SMAD3 protein levels. ..
- Groves M, Johnson C, James J, Prescott A, Cunningham J, Haydock S, et al. p53 and cell cycle independent dysregulation of autophagy in chronic lymphocytic leukaemia. Br J Cancer. 2013;109:2434-44 pubmed publisher..In contrast, Tnv-6 reduces chronic lymphocytic leukaemia (CLL) cell viability with dysregulation of autophagy, without increasing p53-pathway activity...
- Pathak S, Borodkin V, Albarbarawi O, Campbell D, Ibrahim A, van Aalten D. O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. EMBO J. 2012;31:1394-404 pubmed publisher..This is one of the first examples of a single O-GlcNAc site on a signalling protein modulating a key innate immunity signalling pathway. ..
- Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, et al. Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat. 2011;128:783-94 pubmed publisher..This trial presents biomarker evidence for anti-proliferative effects of metformin in women with breast cancer and provides support for therapeutic trials of metformin. ..
- Hardie D. Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism. Proc Nutr Soc. 2011;70:92-9 pubmed publisher..We are working on the hypothesis that this ensures that glycogen synthesis is rapidly activated when glycogen becomes depleted after exercise, but is switched off again as soon as glycogen stores are replenished. ..
- Hamilton D, Philp A, Mackenzie M, Baar K. Prolonged activation of S6K1 does not suppress IRS or PI-3 kinase signaling during muscle cell differentiation. BMC Cell Biol. 2010;11:37 pubmed publisher..The decrease in IRS-1/2 associated p85 together with the increase in phospho-tyrosine associated p85 suggests that PI3K associates primarily with scaffolds other than IRS-1/2 during muscle cell differentiation. ..
- Ginger R, Dalton E, Ryves W, Fukuzawa M, Williams J, Harwood A. Glycogen synthase kinase-3 enhances nuclear export of a Dictyostelium STAT protein. EMBO J. 2000;19:5483-91 pubmed..It also raises the possibility of an analogous regulation of STAT nuclear export in higher eukaryotes. ..
- Leslie N. P-REX2a driving tumorigenesis by PTEN inhibition. Sci Signal. 2009;2:pe68 pubmed publisher..This suggests that aberrant control of PTEN by P-REX2a may represent a key tumorigenic mechanism, in agreement with recent studies supporting the pathological relevance of several other proposed PTEN regulators. ..
- Williams J. STAT signalling in cell proliferation and in development. Curr Opin Genet Dev. 2000;10:503-7 pubmed..Two different ways in which STAT signalling pathways can interface with Smad signalling pathways significantly increasing combinatorial signalling possibilities, have also been described. ..
- Clyde R, Craig A, de Breed L, Bown J, Forrester L, Vojtesek B, et al. A novel ataxia-telangiectasia mutated autoregulatory feedback mechanism in murine embryonic stem cells. J R Soc Interface. 2009;6:1167-77 pubmed publisher..The results point to a possible new target for ATM inhibition that overcomes the restorative potential of the proposed feedback. ..
- van Impel A, Schumacher S, Draga M, Herz H, Grosshans J, Müller H. Regulation of the Rac GTPase pathway by the multifunctional Rho GEF Pebble is essential for mesoderm migration in the Drosophila gastrula. Development. 2009;136:813-22 pubmed publisher..Furthermore, gain-of-function and rescue experiments suggest an important regulatory role of the C-terminal tail of Pbl for the selective activation of Rho1-versus Rac-dependent pathways...
- Mackenzie M, Hamilton D, Murray J, Taylor P, Baar K. mVps34 is activated following high-resistance contractions. J Physiol. 2009;587:253-60 pubmed publisher..2-fold. These data suggest that, following high-resistance contractions, mVps34 activity is stimulated by an influx of essential amino acids such as leucine and this may prolong mTORC1 signalling and contribute to muscle hypertrophy. ..
- Hardie D. AMPK: a key regulator of energy balance in the single cell and the whole organism. Int J Obes (Lond). 2008;32 Suppl 4:S7-12 pubmed publisher..Novel drugs activating AMPK may also have potential for the treatment of obesity. ..
- Watt G, Ismail N, Caballero A, Land S, Wilson S. Epithelial Na? channel activity in human airway epithelial cells: the role of serum and glucocorticoid-inducible kinase 1. Br J Pharmacol. 2012;166:1272-89 pubmed publisher..The maintenance of ENaC activity did, however, depend upon SGK1 and this protein kinase must therefore play an important but permissive role in glucocorticoid-induced ENaC activation. ..
- Groom L, Sneddon A, Alessi D, Dowd S, Keyse S. Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase. EMBO J. 1996;15:3621-32 pubmed
- Anton S, Melville L, Rena G. Epigallocatechin gallate (EGCG) mimics insulin action on the transcription factor FOXO1a and elicits cellular responses in the presence and absence of insulin. Cell Signal. 2007;19:378-83 pubmed..Our results suggest that agents acting in the manner of EGCG may be useful antidiabetic agents. ..
- Hunter R, Treebak J, Wojtaszewski J, Sakamoto K. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Diabetes. 2011;60:766-74 pubmed publisher..We provide genetic evidence that AMPK activation promotes muscle glycogen accumulation by allosteric activation of GS through an increase in glucose uptake and subsequent rise in cellular [G6P]. ..
- Smith H, Liu X, Dai L, Goh E, Chan A, Xi J, et al. The role of TBK1 and IKKÎµ in the expression and activation of Pellino 1. Biochem J. 2011;434:537-48 pubmed publisher..Thus IKKÎµ/TBK1 mediate the activation of Pellino 1's E3 ligase activity, as well as inducing the transcription of its gene and protein expression in response to TLR3 and TLR4 agonists. ..
- Smith T, Tickle C. The expression of Flrt3 during chick limb development. Int J Dev Biol. 2006;50:701-4 pubmed..FLRT3 may have a crucial role in regulating cellular adhesion between the epithelial apical ridge and the underlying mesenchyme and in establishing the dorso-ventral position of the ridge. ..
- Arthur J. MSK activation and physiological roles. Front Biosci. 2008;13:5866-79 pubmed..The physiological roles of MSKs still remain to be completely determined, however recent work has suggested a role for MSKs in neuronal synaptic plasticity and in regulating cytokine production in the innate immune system. ..
- Downes C, Leslie N, Batty I, Van Der Kaay J. Metabolic switching of PI3K-dependent lipid signals. Biochem Soc Trans. 2007;35:188-92 pubmed..We suggest that concomitant inhibition of cysteine-dependent phosphatases, such as PTEN, with activation of SHIP2 functions as a metabolic switch to regulate independently the relative levels of PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). ..
- Ryan R. Cyclic di-GMP signalling and the regulation of bacterial virulence. Microbiology. 2013;159:1286-97 pubmed publisher..Here, I will discuss our recent findings that highlight the role that protein-protein interactions involving these signalling proteins have in regulating functions that contribute to bacterial virulence. ..
- Hadad S, Baker L, Quinlan P, Robertson K, Bray S, Thomson G, et al. Histological evaluation of AMPK signalling in primary breast cancer. BMC Cancer. 2009;9:307 pubmed publisher..Reduced signalling via the AMPK pathway, and the inverse relationship with histological grade and axillary node metastasis, suggests that AMPK re-activation could have therapeutic potential in breast cancer. ..