Abstract
The detection of bacterial signaling molecules in liquid or gaseous environments has been occurring in nature for billions of years. More recently, man-made materials and systems has also allowed for the detection of small molecules in liquid or gaseous environments. This chapter will outline some e...
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PMID: 21031306
PDF is available here.
Ying Yang,
Sébastien Létard,
Laurence Borge,
Amandine Chaix,
Katia Hanssens,
Sophie Lopez,
Marina Vita,
Pascal Finetti,
Daniel Birnbaum,
François Bertucci,
Sophie Gomez,
Paulo de Sepulveda and
Patrice Dubreuil
Abstract
We have described that half of the children carry mutations in extracellular domain (ECD). KIT-ECD versus KIT-PTD mutants were introduced into rodent Ba/F3, EML, Rat2, and human TF1 cells to investigate their biologic effect. Both ECD and PTD mutations induced constitutive receptor autophosphorylati...
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PMID: 20484085
PDF is available here.
Abstract
We report a comprehensive analysis of gck-3 function and demonstrate its requirement for several developmental processes independent of ion homeostasis, i.e., larval progression, vulva, and germ line formation. Consistent with a wide range of gck-3 function we find that endogenous GCK-3 is expressed...
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PMID: 20595048
PDF is available here.
Abstract
We examined the role of PDGFR-beta kinase activity, PDGFR-beta dimerization and PDGFR-beta C-terminal motifs in PDGF-induced PDGFR-beta internalization. We showed that inhibition of PDGFR-beta kinase activity by chemical inhibitor or mutation did not block PDGF-induced PDGFR-beta endocytosis, sugges...
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PMID: 20580638
PDF is available here.
Abstract
We report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small...
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PMID: 20358250
PDF is available here.
Abstract
We demonstrate the early and transient induction of NRP-1 and CRMP-2 in membrane rafts in both ipsilateral and contralateral hemispheres, in contrast to an early, but sustained elevation of Fer kinase and other CRMPs (1, 3, 4, 5) in response to unilateral MCAO. The fact that NRP1/Fer kinase/CRMP-2 c...
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PMID: 20493826
PDF is available here.
Abstract
We show that MRTF-A (Mkl1) and MRTF-B (Mkl2) redundantly control neuronal migration and neurite outgrowth during mouse brain development. Conditional deletion of the genes encoding these Srf coactivators disrupts the formation of multiple brain structures, reflecting a failure in neuronal actin poly...
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PMID: 20534669
PDF is available here.
Abstract
Selenophosphate synthetase 1 (SPS1) is an essential cellular gene in higher eukaryotes. Five alternative splice variants of human SPS1 (major type, DeltaE2, DeltaE8, +E9, +E9a) were identified wherein +E9 and +E9a make the same protein. The major type was localized in both the nuclear and plasma mem...
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PMID: 20471958
PDF is available here.
Abstract
We used RNA interference to explore the function of human kinases and phosphatases in controlling the organization of and trafficking within the secretory pathway. We identified 122 kinases/phosphatases that affect endoplasmic reticulum (ER) export, ER exit sites (ERESs), and/or the Golgi apparatus....
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PMID: 20548102
PDF is available here.
Masamitsu Iwasa,
Hiroyuki Kobayashi,
Shinji Yasuda,
Itta Kawamura,
Shohei Sumi,
Yoshihisa Yamada,
Takeru Shiraki,
Takahiko Yamaki,
Hiroaki Ushikoshi,
Takuma Aoyama,
Kazuhiko Nishigaki,
Genzou Takemura,
Takako Fujiwara,
Hisayoshi Fujiwara and
Shinya Minatoguchi
Abstract
We hypothesized that the alpha-glucosidase inhibitor voglibose, an unabsorbable antidiabetic drug with cardioprotective effects, may act through stimulation of GLP-1 receptors. The results of the present study suggest oral administration of voglibose reduces myocardial infarct size and mitigates car...
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PMID: 20351564
PDF is available here.
Abstract
Various kinases phosphorylate their substrates and thereby switch on or off their functions. Dysregulation of kinases that regulate cell growth signals induces carcinogenesis or malignant phenotypes in cancer. Therefore, kinases are considered to be most promising therapeutic targets in cancer treat...
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PMID: 20535956
PDF is available here.
Guy Lahat,
Asha R Dhuka,
Hen Hallevi,
Lianchun Xiao,
Changye Zou,
Kerrington D Smith,
Thuy L Phung,
Raphael E Pollock,
Robert Benjamin,
Kelly K Hunt,
Alexander J Lazar and
Dina Lev
Abstract
AS harbors a dismal outcome and even patients with disease amenable to complete surgical resection exhibit a 5-year disease-specific survival of only 53%. There is a crucial need for better therapies. Data presented here support further study of the AKT/mTOR pathway as novel molecular targets for AS...
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PMID: 20485141
PDF is available here.
Abstract
We will discuss some of the principles for substrate specificity of enzymes in human nucleotide metabolism illustrated by a selected set of enzyme families where a detailed understanding of the structural determinants for specificity is now emerging.
2010. Published by Elsevier Inc....
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PMID: 20494131
PDF is available here.
Abstract
We report here the first solution structure of this extracellular region. Small-angle X-ray scattering and nuclear magnetic resonance studies show that the four PASTA domains display an unexpected linear organization, contrary to what is observed in the distant protein PBP2x from Streptococccus pneu...
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PMID: 20462494
PDF is available here.
Abstract
We review recent advances in the understanding of the regulatory roles of PTS(Ntr) in various organisms.
Copyright 2010 Elsevier Ltd. All rights reserved....
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PMID: 20202847
PDF is available here.
Abstract
Magnesium is related to a number of biological enzymatic reactions such as catalytic role for the reaction of kinases in ATP production. On the other hand, magnesium is one of the essential minerals for bone formation. In the magnesium-deficient rats, apparent bone loss caused by increase in bone re...
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PMID: 20445288
PDF is available here.
Abstract
We undertake an evolutionary analysis of 53 proteins known either for centriolar association or for involvement in cilia-associated pathologies. By linking protein distribution in 45 diverse eukaryotes with organism biology, we provide molecular evidence to show that basal-body function is ancestral...
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PMID: 20388734
PDF is available here.
Abstract
We demonstrate that the combination of multisite phosphorylation and regulated substrate sequestration can produce a response that is both a good threshold and a good switch. Several strategies are explored, including both stronger and weaker sequestration with successive phosphorylations, as well a...
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PMID: 20409458
PDF is available here.
Abstract
We report here on the molecular basis of this activity. Cell cycle suppression by Cdk5 requires its binding to the p35 activator protein. The related p39 and p25 proteins cannot serve as substitutes. Unexpectedly, Cdk5 enzymatic activity is not required to perform this function. Rather, the link to...
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PMID: 20392944
PDF is available here.
Abstract
We review here the structural and enzymatic properties of the enzymes that carry out the activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of drugs are considered: thymidine analogs, non-n...
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PMID: 20417378
PDF is available here.
Abstract
We use mass spectrometry (MS) to identify 13 phosphorylated residues within APPL1. By using multiple proteases (trypsin, chymotrypsin, and Glu C) and replicate experiments of linear ion trap (LTQ) MS and LTQ-Orbitrap-MS, a combined sequence coverage of 99.6% is achieved. Four of the identified sites...
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PMID: 20095645
PDF is available here.
Abstract
We present the first comprehensive proteomics data set of skinned cardiomyocytes and demonstrate the potential of proteomics to unravel dynamic changes in protein composition that may contribute to the neurohormonal regulation of myofilament contraction....
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PMID: 20037178
PDF is available here.
Abstract
We used field recordings of excitatory post-synaptic potentials (fEPSP) in acute mouse brain slice preparations to study the effects of orexins and pharmacological inhibitors of multiple kinases on long-term synaptic plasticity in the hippocampus.
Orexin-A (OX-A) but not orexin-B (OX...
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PMID: 19624551
PDF is available here.
Jenny J Fischer,
Olivia Y Graebner Baessler,
Christian Dalhoff,
Simon Michaelis,
Anna K Schrey,
Jan Ungewiss,
Kathrin Andrich,
Danny Jeske,
Friedrich Kroll,
Mirko Glinski,
Michael Sefkow,
Mathias Dreger and
Hubert Koester
Abstract
We report the design and application of a novel, fully water-soluble Capture Compound that carries the broadband kinase inhibitor staurosporine as selectivity function. We used this Capture Compound to profile the kinome of the human liver-derived cell line HepG2 and identified one hundred kinases....
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PMID: 20028079
PDF is available here.
Abstract
Key "driver" mutations have been discovered in specific subgroups of non-small-cell lung cancer (NSCLC) patients. Activating mutations in the form of deletions in exon 19 (del 19) or the missense mutation L858R in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) predict outc...
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PMID: 20156777
PDF is available here.
Abstract
Analyses of transgenic sugarcane clones with 45-95% reduced cytosolic pyrophosphate: D-fructose-6-phosphate 1-phosphotransferase (PFP, EC 2.7.1.90) activity displayed no visual phenotypical change, but significant changes were evident in in vivo metabolite levels and fluxes during internode developm...
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PMID: 19957089
PDF is available here.
Abstract
We constructed deletions and missense substitutions in the NarX S helix. Most caused constitutive signaling phenotypes. However, strongly impaired induction phenotypes were conferred by heptad deletions within the S-helix conserved core and also by deletions that remove the heptad stutter. The latte...
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PMID: 19966007
PDF is available here.
Abstract
We show that kinase-active Plk4 is inherently unstable and targeted for degradation. Plk4 is shown to multiply self-phosphorylate within a 24-amino acid phosphodegron. Phosphorylation of multiple sites is required for Plk4 instability, indicating a requirement for a threshold level of Plk4 kinase ac...
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PMID: 20100909
PDF is available here.
Abstract
We employed multiple time scale analysis, Fluctuation Dissipation Theorem, linear stability, and numerical simulations to investigate a module with one positive feedback loop driven by an external stimulus, and we obtained a critical quantity in noise attenuation, termed as "signed activation time"....
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PMID: 20442870
PDF is available here.
Abstract
We survey kinase gene mutations from the perspective of human disease phenotypes and further analyse the structural features of mutant kinases, including mutational hotspots. Our evaluation of the genotype-phenotype relationship across 915 human kinase mutations - that underlie 67 single-gene diseas...
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PMID: 20019687
PDF is available here.
Abstract
We show that a Vav1-talin complex in T cells is a key target for chemokine-triggered inside-out signaling leading to integrin alpha4beta1 activation. Thus, Vav1 dissociation from talin was required to generate high-affinity alpha4beta1 conformations. Assembly of the Vav1-talin complex required PtdIn...
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PMID: 20005136
PDF is available here.
Abstract
We evaluated this technology for studying lipid kinases, class I PI3 kinases, and sphingosine kinases and we show that the assay exhibits good tolerance to different lipids substrates. It generates kinetic parameters for substrates and inhibitors similar to those reported in the literature using oth...
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PMID: 20035616
PDF is available here.
Abstract
We demonstrate the versatility of a luminescent ADP accumulation assay, where one set of reagents can be used for a wide variety of kinases with differing K(m app) for ATP and substrates. Assay sensitivity allows for the use of low enzyme concentrations and small percent ATP conversion levels while...
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PMID: 20059362
PDF is available here.
Abstract
We recently evaluated the ADP-Glo assay from Promega. This is a homogeneous, signal increase assay that measures ADP production from a kinase reaction by coupled enzymes that first convert ADP to ATP and subsequently quantifies ATP using luciferase in the presence of luciferin. Since the unused ATP...
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PMID: 20059376
PDF is available here.
Abstract
ADP-Glo is a novel bioluminescent, homogeneous assay for monitoring ADP producing biochemical reactions and thus it is an ideal assay for detecting enzyme activity using a wide variety of substrates. It is a universal assay that can be used with protein kinases, lipid kinases, sugar kinases, and man...
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PMID: 20105026
PDF is available here.
Abstract
Many assay technologies have been developed and utilized to efficiently assay and screen against protein kinase targets. The radiometric assay format for assaying the protein kinase targets has been considered the "Gold Standard" format since it allows the direct readout of kinase functional activit...
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PMID: 20105027
PDF is available here.
Abstract
We surveyed some of the computational approaches developed to dissect phosphorylation data detected in systematic proteomic experiments and reviewed some experimental and computational approaches used to map phosphorylation sites to their effector kinases in efforts aimed at reconstructing biologica...
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PMID: 19834900
PDF is available here.
Abstract
Classification schemes for disease states can help identify distinctions with useful implications for therapy and prognosis. Speers and colleagues provide a new subclassification scheme for estrogen receptor-negative breast cancer based upon kinome-wide gene expression profiling with interesting fin...
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PMID: 19825953
PDF is available here.
Young Joo Lee,
In Kyu Park,
Moo-Suk Park,
Hye Jin Choi,
Byoung Chul Cho,
Kyung Young Chung,
Se Kyu Kim,
Joon Chang,
Jin Wook Moon,
Hoguen Kim,
Sung Ho Choi and
Joo-Hang Kim
Abstract
Activating mutations within the EGFR TK domain can be used to predict the risk of recurrence in curatively resected pulmonary adenocarcinoma....
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PMID: 19517135
PDF is available here.
Abstract
We present evidence of distinct STI571-induced modulation of abl functions using high-resolution live-cell imaging approaches. Within lamellipodia of fibroblast cells, STI571 was found to induce rapid translocation of abl to the lamellipodium tip. Quantitative analysis yielded 0.81 {micro}M and 1.8...
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PMID: 18835981
PDF is available here.
Abstract
We found that overexpression of the calcineurin homologous protein-1 (CHP1) in opossum kidney cells increased NHE3 transport activity, surface protein abundance, and ezrin phosphorylation. CHP1 knockdown by small interfering RNA had the opposite effects. Overexpression of wild-type ezrin increased b...
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PMID: 19556366
PDF is available here.
Abstract
Our findings suggest that the health-related disparities associated with kinase signaling pathways are more likely to be driven by the genetic variation in the kinase genes than their cognate ligands. Illustrating the role of molecular evolution in the genetic variation of the human kinome could pro...
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PMID: 19644514
PDF is available here.
Qingping Xu,
Dennis Carlton,
Mitchell D Miller,
Marc-André Elsliger,
S Sri Krishna,
Polat Abdubek,
Tamara Astakhova,
Prasad Burra,
Hsiu-Ju Chiu,
Thomas Clayton,
Marc C Deller,
Lian Duan,
Ylva Elias,
Julie Feuerhelm,
Joanna C Grant,
Anna Grzechnik,
Slawomir K Grzechnik,
Gye Won Han,
Lukasz Jaroszewski,
Kevin K Jin,
Heath E Klock,
Mark W Knuth,
Piotr Kozbial,
Abhinav Kumar,
David Marciano,
Daniel McMullan,
Andrew T Morse,
Edward Nigoghossian,
Linda Okach,
Silvya Oommachen,
Jessica Paulsen,
Ron Reyes,
Christopher L Rife,
Natasha Sefcovic,
Christine Trame,
Christina V Trout,
Henry van den Bedem,
Dana Weekes,
Keith O Hodgson,
John Wooley,
Ashley M Deacon,
Adam Godzik,
Scott A Lesley and
Ian A Wilson
Abstract
Cell-cycle-regulated stalk biogenesis in Caulobacter crescentus is controlled by a multistep phosphorelay system consisting of the hybrid histidine kinase ShkA, the histidine phosphotransfer (HPt) protein ShpA, and the response regulator TacA. ShpA shuttles phosphoryl groups between ShkA and TacA. W...
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PMID: 19450606
PDF is available here.
Abstract
We show that increased IP(3) receptor (IP(3)R) sensitivity is initiated at the germinal vesicle breakdown stage of maturation, which correlates with maturation promoting factor (MPF) activation. Extensive phosphopeptide mapping of the IP(3)R resulted in approximately 70% coverage and identified thre...
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PMID: 19473987
PDF is available here.
Abstract
In this paper, a microarray-based surface-enhanced Raman spectroscopic (SERS) assay for detection of kinase functionality and inhibition has been reported. Biotinylated anti-phosphoserinen antibodies mark the phosphorylation and inhibition events and gold nanoparticles are attached t...
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PMID: 19464160
PDF is available here.
Abstract
We consider here a reaction-diffusion model of mutual kinase-receptor activation showing that the strength of positive feedback is controlled by the kinase diffusion coefficient. For high diffusion, the activated kinase molecules quickly leave the vicinity of the cell membrane and cannot efficiently...
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PMID: 19306885
PDF is available here.
Abstract
BCR-ABL1 transcript numbers were monitored in 161 patients who started treatment with imatinib early after diagnosis of chronic myeloid leukaemia in chronic phase and achieved complete cytogenetic responses (CCyR). A confirmed doubling in BCR-ABL1/ABL1 transcript levels was found to be a significant...
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PMID: 19344397
PDF is available here.
Abstract
Lipopolysaccharide (LPS) can activate equine platelets directly or indirectly, via leukocyte-derived platelet activating factor (PAF). Thromboxane (Tx) production by LPS-stimulated equine platelets requires p38 MAPK and this kinase has been suggested as a therapeutic target in endotoxaemia. The pres...
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PMID: 19290950
PDF is available here.
Abstract
We can rank kinases and kinase families based on the likelihood that these kinases are functionally associated with regulating the cell under specific experimental conditions. Such analysis can assist in producing hypotheses that can explain how the kinome is involved in the maintenance of different...
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PMID: 19176546
PDF is available here.
Abstract
During winter, the light-harvesting complexes of evergreen plants change function from energy-harvesting to energy-dissipating centers. The goal of our study was to monitor changes in the composition of the photosynthetic apparatus that accompany these functional changes. Seasonal changes in chlorop...
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PMID: 19203960
PDF is available here.
Abstract
We studied the developmental regulation of tau in rats during development from embryonic day 15 through the age of 24 months. We found that tau expression increased sharply during the embryonic stage and then became relatively stable, whereas tau phosphorylation was much higher in developing brain t...
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PMID: 19183272
PDF is available here.
Abstract
Ornithobacterium rhinotracheale (ORT) is a bacterium common to commercial poultry and wild birds throughout the world. It is also known as a causative agent of respiratory diseases. A total of 93 ORT isolates originating from chickens, pigeons, ostriches, quail, turkeys, and an Asian crested goshawk...
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PMID: 19432012
PDF is available here.
Abstract
We demonstrate this region is required for activation of the SphS-SphR phosphate-sensing two-component system under phosphate-limiting conditions and mutants lacking this extension do not show constitutive alkaline phosphatase activity when the negative regulator SphU is inactivated. We have also id...
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PMID: 19013133
PDF is available here.
Abstract
NS5A phosphorylation can be studied in two ways: in living cells and in vitro. The former has several advantages: NS5A phosphorylation takes place in a cellular background and therefore might mimic more closely the real in vivo situation. Viral proteins and cellular kinases are in the correct cellul...
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PMID: 19009256
PDF is available here.
Abstract
We review critical mechanisms of asthma development and discuss how kinases and phosphatases are likely to regulate the development of disease through their effect on these various mechanisms....
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PMID: 20001889
PDF is available here.
Abstract
We designed two point mutations, Q513L and Q513N, and monitored the effects on the chromophore and protein using a combination of UV-visible absorbance and circular dichroism spectroscopy, limited proteolysis, and solution NMR. The results show that these mutations significantly dampen the changes b...
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PMID: 19063612
PDF is available here.
Abstract
We developed a three-component chemical reaction which converts the transient noncovalent substrate-kinase complex into a covalently cross-linked product by utilizing a dialdehyde-based cross-linker, 1. Unfortunately, the reaction of 1 with a lysine in the kinase active site and an engineered cystei...
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PMID: 19053485
PDF is available here.
Abstract
More than 500 compounds chosen to represent kinase inhibitor space have been screened against a panel of over 200 protein kinases. Significant results include the identification of hits against new kinases including PIM1 and MPSK1, and the expansion of the inhibition profiles of several literature c...
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PMID: 19035792
PDF is available here.