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71.
Yvonne Welte James Adjaye Hans R Lehrach Christian RA Regenbrecht 《Cell communication and signaling : CCS》2010,8(1):1-10
Background
The fibroblast growth factor receptor (FGFR) interprets concentration gradients of FGF ligands and structural changes in the heparan sulfate (HS) co-receptor to generate different cellular responses. However, whether the FGFR generates different signals is not known.Results
We have previously shown in rat mammary fibroblasts that in cells deficient in sulfation, and so in HS co-receptor, FGF-2 can only stimulate a transient phosphorylation of p42/44MAPK and so cannot stimulate DNA synthesis. Here we demonstrate that this is because in the absence of HS, FGF-2 fails to stimulate the phosphorylation of the adaptor FGFR substrate 2 (FRS2). In cells possessing the HS co-receptor, FGF-2 elicits a bell-shaped dose response: optimal concentrations stimulate DNA synthesis, but supramaximal concentrations (≥ 100 ng/mL) have little effect. At optimal concentrations (300 pg/mL) FGF-2 stimulates a sustained dual phosphorylation of p42/44MAPK and tyrosine phosphorylation of FRS2. In contrast, 100 ng/mL FGF-2 only stimulates a transient early peak of p42/44MAPK phosphorylation and fails to stimulate appreciably the phosphorylation of FRS2 on tyrosine.Conclusions
These results suggest that the nature of the FGFR signal produced is determined by a combination of the HS co-receptor and the concentration of FGF ligand. Both the phosphorylation of the adaptor FRS2, the kinetics (sustained or transient) of phosphorylation of p42/44(MAPK) are varied, and so differing cellular responses are produced. 相似文献72.
GW Patton R Stephens IA Sidorov X Xiao RA Lempicki DS Dimitrov RH Shoemaker G Tudor 《BMC bioinformatics》2006,7(1):81
Background
Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes. 相似文献73.
74.
NÓRA BREZA JÁNOS PATÓ LÁSZLÓ ŐRFI BÁLINT HEGYMEGI-BARAKONYI PÉTER BÁNHEGYI EDIT VÁRKONDI 《Journal of receptor and signal transduction research》2013,33(4):361-373
The development of selective protein kinase inhibitors has become an important area of drug discovery for the treatment of different diseases. We report the synthesis and characterization of a series of novel quinazoline derivatives against three therapeutically important and pharmacologically related kinases: 1) epidermal growth factor receptor (EGFR; wild type and mutant) in the field of cancer, 2) receptor-interacting caspase-like apoptosis-regulatory kinase (RICK) in the field of inflammation, and 3) pUL97 of human cytomegalovirus (HCMV). For reference purpose we have synthesized the four clinically relevant quinazolines, including the lead compounds, which we previously identified for RICK and pUL97. A total of 52 quinazoline derivatives were synthesized and tested on the basis of these leads to specifically target the hydrophobic pocket of the ATP-binding site. Selected compounds were tested on wild-type and mutant forms of EGFR, RICK, and pUL97 kinases; their logP and logS values for assessing suitability as drugs were calculated and hit or lead compounds identified. 相似文献
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76.
Accurate estimates of the fertilization effect that elevated carbon dioxide [CO2] has on crop yields are valuable for estimation of future crop production, yet there is still some controversy over these estimates due to possible CO2‐by‐water‐status interactions in chamber studies and the difficulty of conducting field experiments with elevated [CO2]. This study presents a new method to estimate the CO2 fertilization effect (CFE) in dry conditions (CFEdry), based on a combination of historical yield and climatic data and field experiments that do not require elevated [CO2]. It was estimated that approximately 50 years of increasing [CO2] (i.e., a 73 ppm increase) resulted in a 9% and 14% improvement of yield in dry conditions for maize and soybean, respectively, which are similar to estimates derived from free air CO2 enrichment (FACE) studies. The main source of uncertainty in this approach relates to differential effects of technology trends such as new cultivars in wet vs. dry years. Estimates of this technology–water interaction can be refined by further experimentation under ambient [CO2], offering a cost‐effective path for improving CFE estimates. The results should prove useful for modeling future yield impacts of climate change, and the approach could be used to derive estimates for other species using relatively simple yield trials. 相似文献
77.
SEBASTIÁN APESTEGUÍA RAÚL O. GÓMEZ GUILLERMO W. ROUGIER 《Zoological Journal of the Linnean Society》2012,166(2):342-360
Herein we describe a new rhynchocephalian taxon from the Middle Jurassic of Patagonia, Argentina, representing the first Jurassic record of the group in South America. The new taxon, consisting of a complete dentary, is ascribed to Sphenodontia based on the presence of a deep and wide Meckelian groove, long posterior process, well‐developed coronoid process, and acrodont teeth showing dental regionalization including successional, alternate hatchling, and additional series. This allocation is reinforced by a phylogenetic analysis that places the new taxon in a basal position within a clade of sphenodontians that excludes Diphydontosaurus and Planocephalosaurus. Additionally, the new taxon clusters within a Gondwanan clade with the Indian Godavarisaurus from the Jurassic Kota Formation, sharing the presence of recurved and relatively large posterior successional teeth that are ribbed and bear a peculiar anterolingual groove. This sister‐group relationship is intriguing from a palaeobiogeographical viewpoint, as it suggests some degree of endemism during the initial stages of the breakup of Pangaea. We also discuss the ontogenetic stage of the new taxon and provide insights on the evolution of successional dentition in rhynchocephalians. © 2012 The Linnean Society of London, Zoological Journal of the Linnean Society, 2012, 166 , 342–360. 相似文献
78.
79.
Background
Ran GTPase has multiple functions during the cell division cycle, including nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. The activity of Ran is determined by both its guanine nucleotide-bound state and its subcellular localization. 相似文献80.
Randa A Abusham RA Noor Zaliha Raja Rahman Abu Bakar Salleh Mahiran Basri 《Microbial cell factories》2009,8(1):20-9