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991.
Abstract: Monoamine-activated α2-macroglobulin (α2M) was shown to reduce the dopamine concentration in corpus striatum of adult rat brains and inhibit other neuronal functions in vivo and in vitro. As brain-derived neurotrophic factor, neurotrophin-4, and neurotrophin-3 are important neurotrophic factors for dopaminergic neurons, the effect of monoamine-activated α2M on signal transduction by trkB and trkC was investigated. The results show that monoamine-activated α2M binds to trkB and inhibits brain-derived neurotrophic factor/neurotrophin-4-promoted autophosphorylation of trkB in a dose-dependent manner in both trkB-expressing NIH3T3 (NIH3T3-trkB) and human neuroblastoma SH-SY5Y cells. Monoamine-activated α2M also blocks tyrosine phosphorylation of phospholipase C-γ1 and extracellular signal-regulated protein kinase (ERK)-1, which are key intracellular proteins involved in trkB signal transduction. Similarly, monoamine-activated α2M inhibits tyrosine phosphorylation of neurotrophin-3-induced trkC and its signal transduction in a dose-dependent manner in NIH3T3 cells expressing trkC (NIH3T3-trkC). In contrast to monoamine-activated α2M, normal α2M has little or no significant inhibitory effect on the phosphorylation of trkB and trkC. In addition, the retinoic acid-promoted tyrosine phosphorylation of phospholipase C-γ1, ERK-1, and/or ERK-2 in SH-SY5Y cells was unaffected by monoamine-activated α2M; this suggests that the inhibitory effect of activated α2M on the neurotrophin-stimulated phosphorylation of intracellular signalling proteins may be specific. Taken together, the data indicate that activated α2M is a pan-trk inhibitor, which by virtue of its binding to trk receptors may block trk-mediated signal transduction in dopaminergic neurons and lead to reduction of dopamine concentration in corpus striatum. 相似文献
992.
Po-Han Chen Xiaoyan ChenXiaolin He 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(10):2176-2186
The four types of platelet-derived growth factors (PDGFs) and the two types of PDGF receptors (PDGFRs, which belong to class III receptor tyrosine kinases) have important functions in the development of connective tissue cells. Recent structural studies have revealed novel mechanisms of PDGFs in propeptide loading and receptor recognition/activation. The detailed structural understanding of PDGF–PDGFR signaling has provided a template that can aid therapeutic intervention to counteract the aberrant signaling of this normally silent pathway, especially in proliferative diseases such as cancer. This review summarizes the advances in the PDGF system with a focus on relating the structural and functional understandings, and discusses the basic aspects of PDGFs and PDGFRs, the mechanisms of activation, and the insights into the therapeutic antagonism of PDGFRs. This article is part of a Special Issue entitled: Emerging recognition and activation mechanisms of receptor tyrosine kinases. 相似文献
993.
Laura Malki-Feldman 《Experimental parasitology》2009,123(1):39-4237
Effect of modulators on protein kinase A (PKA) activity, promastigote growth and their ability to infect peritoneal macrophages was monitored. PKA inhibitors reduced [Protein Kinase Inhibitor (PKI) - 56%; H89 - 54.5%] kemptide phosphorylation by Leishmania major promastigote lysates, while activators increased phosphorylation (8-CPT-cAMP - 88%; Sp-cAMPS-AM - 152%). Activation was specifically inhibited by PKI. Phosphodiesterase inhibitors also increased kemptide phosphorylation (dipyridamole - 171%; rolipram - 106%; and 3-isobutyl-1-methyl-xanthine - 154%). Parasite proliferation was significantly retarded (200 nM H89; 100 μM myristoylated-PKI) or completely inhibited (500 nM H89) by culturing with PKA inhibitors. Incubation with dipyridamole or Sp-cAMPS-AM also inhibited proliferation. Brief treatment (2 h) with either H89, myristoylated-PKI, dipyridamole or Sp-cAMPS-AM reduced initial macrophage infection at days 1 and 2 (>40%) and on day 3 (>78% only for 100 μM myr-PKI). Characterization of leishmanial cAMP mediated signal transduction pathways will serve as the basis for the new drug design. 相似文献
994.
Eric A. Balcueva Qin Wang Heather Hughes Charles Kunsch Zihui Yu Janet D. Robishaw 《Experimental cell research》2000,257(2):310
The mammalian γ subunit family consists of a minimum of 12 members. Analysis of the amino acid sequence conservation suggests that the γ subunit family can be divided into three distinct subclasses. The division of the γ subunit family into these classes is based not only on amino acid homology, but also to some extent on functional similarities. In the present study, two new members of the γ subunit family, the γ11 and γ14 subunits, are identified and characterized in terms of their expression and function. The γ11 and γ14 subunits are most closely related to the γ1 subunit and share similar biochemical properties, suggesting their inclusion in class I. However, despite their close phylogenetic relationship and similar biochemical properties, the γ1, γ11, and γ14 subunits exhibit very distinct expression patterns, suggesting that class I should be further subdivided and that the signaling functions of each subgroup are distinct. In this regard, the γ11 and γ14 subunits represent a new subgroup of farnesylated γ subunits that are expressed outside the retina and have functions other than phototransduction. 相似文献
995.
Summary Recent fluorescence, AVEC-DIC, and confocal laser scanning microscopic studies have revealed the dynamic nature and structural extent of a calcium-sequestering endoplasmic reticulum (ER) in plant cells. Various investigators have proposed different roles for the ER in cell motility. One, the ER plays a direct role in the generation of intracellular particle motions or two, the ER regulates particle motions indirectly. We show that the ER can be extruded fromAcetabularia cells, stains brightly with the fluorescent dye DiOC6(3), and small (ca. 100 nm diameter) fluorescent vesicles are observed to move in or along the ER tubules. Intracellular particle movements in the giant algal cellAcetabularia can be transiently inhibited by IP4, IP3, and IP2, compounds which in animal cells are known to cause the release of free calcium ions. A model is proposed which clarifies the possible relationships between the ER, calciosomes, calcium ions, and the microfilament-generated intracellular particle movements observed in plant cells.Abbreviations AVEC-DIC
video microscopy in differential interference contrast
- CFLSM
confocal laser scanning microscope
- DiOC6(3)
3,3-dihexyloxacarbocyanine iodide
- ER
endoplasmic reticulum
- IP3
inositol triphosphate
- N.A.
numerical aperture
- SIT
silicon intensified target video camera
- SR
sarcoplasmic reticulum 相似文献
996.
Light perception in guard cells 总被引:2,自引:1,他引:1
E. ZEIGER 《Plant, cell & environment》1990,13(7):739-744
Abstract. Guard cells perceive light via two photoreceptor systems: a blue-light-dependent photosystem and the guard cell chloroplast. Chloroplasts stimulate stomatal opening by transducing photosynthetic active radiation into proton pumping at the guard cell plasma membrane. In addition, guard cell chloroplasts fix CO2 photosynthetically. Sugar from guard cell photosynthesis can contribute to the osmotic build-up required for opening. The blue-light-dependent photosystem activates proton pumping at the guard cell plasma membrane and stimulates starch hydrolysis. Available information on the photobiological properties of guard cells makes it possible to describe stomatal function in terms of the cellular components regulating stomatal movements. The blue light response is involved in stomatal opening in the early morning and stomatal responses to sunflecks. The guard cell chloroplast is likely to be involved in stomatal adaptations to sun, shade and to temperature. Interactions between these photosystems, a third photoreceptor in guard cells, phytochrome, and other mechanisms transducing stomatal responses such as VPD and carbon dioxide, provide the cellular basis for stomatal regulation. 相似文献
997.
An adenylate cyclase activity of 16.02±1.03 pmol cAMP produced min−1 (mg protein)−1 was detected in a cell homogenate ofDunaliella viridis, a unicellular halotolerant green alga. It was present in both the membrane fraction and soluble fraction separated from
the homogenate. Adenylate cyclase activity in the homogenate was activated by 1μM GTPγS but not by Ca2++calmodulin, suggesting this enzyme to be regulated by a G-protein. A phosphodiesterase activity of 23.12±15.03 pmol cAMP
decomposed min−1 (mg protein)−1 was found in the homogenate. These activities suggest the presence of a cAMP mediated signal transduction system inDunaliella. Cells, transferred from 1.7 M NaCl medium to 1 M NaCl, showed rapid increase in cAMP within 2 min to about 1.5 times the
original concentration (from 2.4±0.2 to 3.9±0.2 pmol per 108 cells) which was recovered in 30 min. 相似文献
998.
Hydrodynamic shear stress and mass transport modulation of endothelial cell metabolism 总被引:11,自引:0,他引:11
Mammalian cells responds to physical forces by altering their growth rate, morphology, metabolism, and genetic expression. We have studied the mechanism by which these cells detect the presence of mechanical stress and convert this force into intracellular signals. As our model systems, we have studied cultured human endothelial cells, which line the blood vessels and forms the interface between the blood and the vessel wall. These cell responds within minutes to the initiation of flow by increasing their arachidonic acid metabolism and increasing the level of the intracellular second messengers inositol trisphosphate and calcium ion concentration. With continued exposure to arterial levels of wall shear stress for up to 24 h, endothelial cells increase the expression of tissue plasminogen activator (tPA) and tPA messenger RNA (mRNA) and decrease the expression of endothelin peptide and endothelin mRNA. Since the initiation of flow also causes enhanced convective mass transfer to the endothelial cell monolayer, we have investigated the role of enhanced convection of adenosine trisphosphate (ATP) to the cell surface in eliciting a cellular response by monitoring cytosolic calcium concentrations on the single cell level and by computing the concentration profile of ATP in a parallel-plate flow geometry. Our result demonstrate that endothelial cells respond in very specific ways to the initiation of flow and that mass transfer and fluid shear stress can both play a role in the modulation of intracellular signal transduction and metabolism. 相似文献
999.
Cloning of mini-mu bacteriophage in cosmids: in vivo packaging into phage lambda heads 总被引:1,自引:0,他引:1
A technique has been developed that permits the packaging of mini-Mu-carrying cosmids into phage lambda heads. This procedure has several advantages over packaging into Mu helper capsids: the amounts of DNA to be packaged can be increased, the packaging efficiency is improved, and the stability of transducing lysates is high. 相似文献
1000.
Abstract The generalized transducing phage P1 grew well on heterozygous Escherichia coli carrying recA srlC 300::Tn 10 on the chromosome and recA + on a pBR322-derived plasmid. Because of the close linkage of Tn 10 to recA mutations, including recA 1, recA 13, recA 56, recA deletion and recA allele of E. coli BNG30, the latter can be moved to other strains in transductional crosses for selective resistance to tetracycline. 相似文献