PubMed Central (PMC3 - NLM DTD)
(2,081,148 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 81 - 100 de 9,978
81.
Cell Surface Transglutaminase Promotes RhoA Activation via Integrin Clustering and Suppression of the Srcp190RhoGAP Signaling PathwayD? - Janiak, Anna; Zemskov, Evgeny A.; Belkin, Alexey M.
Tissue transglutaminase (tTG) is a multifunctional protein that serves as cross-linking enzyme and integrin-binding adhesion coreceptor for fibronectin on the cell surface. Previous work showed activation of small GTPase RhoA via enzymatic transamidation by cytoplasmic tTG. Here, we report an alternative nonenzymatic mechanism of RhoA activation by cell surface tTG. Direct engagement of surface tTG with specific antibody or the fibronectin fragment containing modules I6II1,2I7-9 increases RhoA-GTP levels. Integrin-dependent signaling to RhoA and its downstream target Rho-associated coiled-coil containing serine/threonine protein kinase (ROCK) is amplified by surface tTG. tTG expression on the cell surface elevates RhoA-GTP levels in nonadherent and...
82.
Calpain Mediates a von Hippel-Lindau Proteinindependent Destruction of Hypoxia-inducible Factor-1? - Zhou, Jie; Köhl, Roman; Herr, Barbara; Frank, Ronald; Brüne, Bernhard
Hypoxia-inducible factor 1 (HIF-1) is controlled through stability regulation of its alpha subunit, which is expressed under hypoxia but degraded under normoxia. Degradation of HIF-1? requires association of the von Hippel Lindau protein (pVHL) to provoke ubiquitination followed by proteasomal digestion. Besides hypoxia, nitric oxide (NO) stabilizes HIF-1? under normoxia but destabilizes the protein under hypoxia. To understand the role of NO under hypoxia we made use of pVHL-deficient renal carcinoma cells (RCC4) that show a high steady state HIF-1? expression under normoxia. Exposing RCC4 cells to hypoxia in combination with the NO donor DETA-NO (2,2?-(hydroxynitrosohydrazono) bis-ethanimine), but not hypoxia...
83.
A Role for PP1 in the Cdc2/Cyclin Bmediated Positive Feedback Activation of Cdc25 - Margolis, Seth S.; Perry, Jennifer A.; Weitzel, Douglas H.; Freel, Christopher D.; Yoshida, Minoru; Haystead, Timothy A.; Kornbluth, Sally
The Cdc25 phosphatase promotes entry into mitosis through the removal of inhibitory phosphorylations on the Cdc2 subunit of the Cdc2/CyclinB complex. During interphase, or after DNA damage, Cdc25 is suppressed by phosphorylation at Ser287 (Xenopus numbering; Ser216 of human Cdc25C) and subsequent binding of the small acidic protein, 14-3-3. As reported recently, at the time of mitotic entry, 14-3-3 protein is removed from Cdc25 and S287 is dephosphorylated by protein phosphatase 1 (PP1). After the initial activation of Cdc25 and consequent derepression of Cdc2/CyclinB, Cdc25 is further activated through a Cdc2-catalyzed positive feedback loop. Although the existence of such a...
84.
The Saccharomyces cerevisiae Spindle Pole Body (SPB) Component Nbp1p Is Required for SPB Membrane Insertion and Interacts with the Integral Membrane Proteins Ndc1p and Mps2pD? - Araki, Yasuhiro; Lau, Corine K.; Maekawa, Hiromi; Jaspersen, Sue L.; Giddings, Thomas H.; Schiebel, Elmar; Winey, Mark
The spindle pole body (SPB) in Saccharomyces cerevisiae functions to nucleate and organize spindle microtubules, and it is embedded in the nuclear envelope throughout the yeast life cycle. However, the mechanism of membrane insertion of the SPB has not been elucidated. Ndc1p is an integral membrane protein that localizes to SPBs, and it is required for insertion of the SPB into the nuclear envelope during SPB duplication. To better understand the function of Ndc1p, we performed a dosage suppressor screen using the ndc1-39 temperature-sensitive allele. We identified an essential SPB component, Nbp1p. NBP1 shows genetic interactions with several SPB genes...
85.
Kiss-and-Coat and Compartment Mixing: Coupling Exocytosis to Signal Generation and Local Actin Assembly - Sokac, Anna M.; Bement, William M.
Regulated exocytosis is thought to occur either by full fusion, where the secretory vesicle fuses with the plasma membrane (PM) via a fusion pore that then dilates until the secretory vesicle collapses into the PM; or by kiss-and-run, where the fusion pore does not dilate and instead rapidly reseals such that the secretory vesicle is retrieved almost fully intact. Here, we describe growing evidence for a third form of exocytosis, dubbed kiss-and-coat, which is characteristic of a broad variety of cell types that undergo regulated exocytosis. Kiss-and-coat exocytosis entails prolonged maintenance of a dilated fusion pore and assembly of actin...
86.
Activity- and Calcineurin-independent Nuclear Shuttling of NFATc1, but Not NFATc3, in Adult Skeletal Muscle Fibers - Shen, Tiansheng; Liu, Yewei; Cseresnyés, Zoltán; Hawkins, Arie; Randall, William R.; Schneider, Martin F.
The transcription factor NFATc1 may be involved in slow skeletal muscle gene expression. NFATc1 translocates from cytoplasm to nuclei during slow fiber type electrical stimulation of skeletal muscle fibers because of activation of the Ca2+-dependent phosphatase calcineurin, resulting in nuclear factor of activated T-cells (NFAT) dephosphorylation and consequent exposure of its nuclear localization signal. Here, we find that unstimulated adult skeletal muscle fibers exhibit a previously unanticipated nucleocytoplasmic shuttling of NFATc1 without appreciable nuclear accumulation. In resting fibers, the nuclear export inhibitor leptomycin B caused nuclear accumulation of NFATc1 (but not of isoform NFATc3) and formation of NFATc1 intranuclear bodies...
87.
Thioredoxin-mediated Negative Autoregulation of Peroxisome Proliferator-activated Receptor ? Transcriptional Activity - Liu, Guang-Hui; Qu, Jing; Shen, Xun
PPAR?, a member of the nuclear receptor superfamily, and thioredoxin, a critical redox-regulator in cells, were found to form a negative feedback loop, which autoregulates transcriptional activity of PPAR?. Thioredoxin was identified as a target gene of PPAR?. Activation of PPAR? leads to increase of thioredoxin expression as well as its translocation from cytoplasm to nucleus, whereas ectopic overexpression of thioredoxin in the nucleus dramatically inhibited both constitutive and ligand-dependent PPAR? activation. As PPAR?-target genes, the expression of muscle carnitine palmitoyltransferase I, medium chain acyl CoA dehydrogenase, and apolipoprotein A-I were significantly down-regulated by nucleus-targeted thioredoxin at transcriptional or protein...
88.
Protein Kinase C? Attenuates Hypoxia-induced Proliferation of Fibroblasts by Regulating MAP Kinase Phosphatase-1 Expression - Short, Megan D.; Fox, Stephanie M.; Lam, Ching F.; Stenmark, Kurt R.; Das, Mita
We have previously found that hypoxia stimulates proliferation of vascular fibroblasts through G?i-mediated activation of ERK1/2. Here, we demonstrate that hypoxia also activates the atypical protein kinase C? (PKC?) isozyme and stimulates the expression of ERK1/2-specific phosphatase, MAP kinase phosphatase-1 (MKP-1), which attenuates ERK1/2-mediated proliferative signals. Replication repressor activity is unique to PKC? because the blockade of classical and novel PKC isozymes does not affect fibroblast proliferation. PKC? is phosphorylated upon prolonged (24 h) exposure to hypoxia, whereas ERK1/2, the downstream kinases, are maximally activated in fibroblasts exposed to acute (10 min) hypoxia. However, PKC? blockade results in persistent ERK1/2...
89.
Role of LIM Kinases in Normal and Psoriatic Human Epidermis - Honma, Masaru; Benitah, Salvador Aznar; Watt, Fiona M.
We present evidence that LIM kinases can control cell adhesion and compaction in human epidermis. LIMK2 is expressed in the epidermal basal layer and signals downstream of the GTPase Rac1 to promote extracellular matrix adhesion and inhibit terminal differentiation. Conversely, LIMK1 is expressed in the upper granular layers and phosphorylates and inhibits cofilin. Expression of LIMK1 is lost in psoriatic lesions and other skin disorders characterized by lack of cell compaction in the differentiating cell layers. In psoriatic lesions down-regulation of LIMK1 correlates with up-regulation of Myc. Expression of constitutively active cofilin or Myc in reconstituted human epidermis blocks cell...
90.
SUMOylation of the Corepressor N-CoR Modulates Its Capacity to Repress Transcription - Tiefenbach, Jens; Novac, Natalia; Ducasse, Miryam; Eck, Maresa; Melchior, Frauke; Heinzel, Thorsten
In the absence of ligands the corepressor N-CoR mediates transcriptional repression by some nuclear hormone receptors. Several proteinprotein interactions of N-CoR are known, of which mainly complex formation with histone deacetylases (HDACs) leads to the repression of target genes. On the other hand, the role of posttranslational modifications in corepressor function is not well established. Here, we show that N-CoR is modified by Sumo-1. We found SUMO-E2conjugating enzyme Ubc9 and SUMO-E3 ligase Pias1 as novel N-CoR interaction partners. The SANT1 domain of N-CoR was found to mediate this interaction. We show that K152, K1117, and K1330 of N-CoR can be...
91.
Distinct Roles of PI(3,4,5)P3 during Chemoattractant Signaling in Dictyostelium: A Quantitative In Vivo Analysis by Inhibition of PI3-KinaseV? - Loovers, Harriët M.; Postma, Marten; Keizer-Gunnink, Ineke; Huang, Yi Elaine; Devreotes, Peter N.; van Haastert, Peter J.M.
The role of PI(3,4,5)P3 in Dictyostelium signal transduction and chemotaxis was investigated using the PI3-kinase inhibitor LY294002 and pi3k-null cells. The increase of PI(3,4,5)P3 levels after stimulation with the chemoattractant cAMP was blocked >95% by 60 ?M LY294002 with half-maximal effect at 5 ?M. This correlated well with the inhibition of the membrane translocation of the PH-domain protein, PHcracGFP. LY294002 did not reduce cAMP-mediated cGMP production, but significantly reduced the cAMP response up to 75% in wild type and completely in pi3k-null cells. LY294002-treated cells were round, not elongated as control cells. Interestingly, cAMP induced a time and dose-dependent recovery...
92.
Interacting Protein Kinases Involved in the Regulation of Flagellar Length - Erdmann, Maja; Scholz, Anne; Melzer, Inga M.; Schmetz, Christel; Wiese, Martin
A striking difference of the life stages of the protozoan parasite Leishmania is a long flagellum in the insect stage promastigotes and a rudimentary organelle in the mammalian amastigotes. LmxMKK, a mitogen-activated protein (MAP) kinase kinase from Leishmania mexicana, is required for growth of a full-length flagellum. We identified LmxMPK3, a MAP kinase homologue, with a similar expression pattern as LmxMKK being not detectable in amastigotes, up-regulated during the differentiation to promastigotes, constantly expressed in promastigotes, and shut down during the differentiation to amastigotes. LmxMPK3 null mutants resemble the LmxMKK knockouts with flagella reduced to one-fifth of the wild-type length,...
93.
Heteromerization of Innexin Gap Junction Proteins Regulates Epithelial Tissue Organization in Drosophila - Lehmann, Corinna; Lechner, Hildegard; Löer, Birgit; Knieps, Martin; Herrmann, Sonja; Famulok, Michael; Bauer, Reinhard; Hoch, Michael
Gap junctions consist of clusters of intercellular channels, which enable direct cell-to-cell communication and adhesion in animals. Whereas deuterostomes, including all vertebrates, use members of the connexin and pannexin multiprotein families to assemble gap junction channels, protostomes such as Drosophila and Caenorhabditis elegans use members of the innexin protein family. The molecular composition of innexin-containing gap junctions and the functional significance of innexin oligomerization for development are largely unknown. Here, we report that heteromerization of Drosophila innexins 2 and 3 is crucial for epithelial organization and polarity of the embryonic epidermis. Both innexins colocalize in epithelial cell membranes. Innexin3 is...
94.
Functional Estrogen Receptors in the Mitochondria of Breast Cancer Cells - Pedram, Ali; Razandi, Mahnaz; Wallace, Douglas C.; Levin, Ellis R.
Steroid hormones have been reported to indirectly impact mitochondrial functions, attributed to nuclear receptor-induced production of proteins that localize in this cytoplasmic organelle. Here we show high-affinity estrogen receptors in the mitochondria of MCF-7 breast cancer cells and endothelial cells, compatible with classical estrogen receptors ER? and ER?. We report that in MCF-7, estrogen inhibits UV radiation-induced cytochrome C release, the decrease of the mitochondrial membrane potential, and apoptotic cell death. UV stimulated the formation of mitochondrial reactive oxygen species (mROS), and mROS were essential to inducing mitochondrial events of cell death. mROS mediated the UV activation of c-jun N-terminal...
95.
The Mcp Element Mediates Stable Long-Range ChromosomeChromosome Interactions in DrosophilaV? - Vazquez, Julio; Müller, Martin; Pirrotta, Vincenzo; Sedat, John W.
Chromosome organization inside the nucleus is not random but rather is determined by a variety of factors, including interactions between chromosomes and nuclear components such as the nuclear envelope or nuclear matrix. Such interactions may be critical for proper nuclear organization, chromosome partitioning during cell division, and gene regulation. An important, but poorly documented subset, includes interactions between specific chromosomal regions. Interactions of this type are thought to be involved in long-range promoter regulation by distant enhancers or locus control regions and may underlie phenomena such as transvection. Here, we used an in vivo microscopy assay based on Lac Repressor/operator...
96.
Casein Kinase II and Calcineurin Modulate TRPP Function and Ciliary LocalizationD? - Hu, Jinghua; Bae, Young-Kyung; Knobel, Karla M.; Barr, Maureen M.
Cilia serve as sensory devices in a diversity of organisms and their defects contribute to many human diseases. In primary cilia of kidney cells, the transient receptor potential polycystin (TRPP) channels polycystin-1 (PC-1) and polycystin-2 (PC-2) act as a mechanosensitive channel, with defects resulting in autosomal dominant polycystic kidney disease. In sensory cilia of Caenorhabditis elegans male-specific neurons, the TRPPs LOV-1 and PKD-2 are required for mating behavior. The mechanisms regulating TRPP ciliary localization and function are largely unknown. We identified the regulatory subunit of the serine-threonine casein kinase II (CK2) as a binding partner of LOV-1 and human PC-1....
97.
Rac3-induced Neuritogenesis Requires Binding to Neurabin I - Orioli, Donata; Colaluca, Ivan N.; Stefanini, Miria; Riva, Silvano; Dotti, Carlos G.; Peverali, Fiorenzo A.
Rac3, a neuronal GTP-binding protein of the Rho family, induces neuritogenesis in primary neurons. Using yeast two-hybrid analysis, we show that Neurabin I, the neuronal F-actin binding protein, is a direct Rac3-interacting molecule. Biochemical and light microscopy studies indicate that Neurabin I copartitions and colocalizes with Rac3 at the growth cones of neurites, inducing Neurabin I association to the cytoskeleton. Moreover, Neurabin I antisense oligonucleotides abolish Rac3-induced neuritogenesis, which in turn is rescued by exogenous Neurabin I but not by Neurabin I mutant lacking the Rac3-binding domain. These results show that Neurabin I mediates Rac3-induced neuritogenesis, possibly by anchoring Rac3...
98.
Mutations of the Drosophila Zinc Finger-encoding Gene vielfältig Impair Mitotic Cell Divisions and Cause Improper Chromosome SegregationV? - Staudt, Nicole; Fellert, Sonja; Chung, Ho-Ryun; Jäckle, Herbert; Vorbrüggen, Gerd
We describe the molecular characterization and function of vielfältig (vfl), a X-chromosomal gene that encodes a nuclear protein with six Krüppel-like C2H2 zinc finger motifs. vfl transcripts are maternally contributed and ubiquitously distributed in eggs and preblastoderm embryos, excluding the germline precursor cells. Zygotically, vfl is expressed strongly in the developing nervous system, the brain, and in other mitotically active tissues. Vfl protein shows dynamic subcellular patterns during the cell cycle. In interphase nuclei, Vfl is associated with chromatin, whereas during mitosis, Vfl separates from chromatin and becomes distributed in a granular pattern in the nucleoplasm. Functional gain-of-function and lack-of-function...
99.
The Ras-GRF1 Exchange Factor Coordinates Activation of H-Ras and Rac1 to Control Neuronal MorphologyD? - Yang, Huibin; Mattingly, Raymond R.
The Ras-GRF1 exchange factor has regulated guanine nucleotide exchange factor (GEF) activity for H-Ras and Rac1 through separate domains. Both H-Ras and Rac1 activation have been linked to synaptic plasticity and thus could contribute to the function of Ras-GRF1 in neuronal signal transduction pathways that underlie learning and memory. We defined the effects of Ras-GRF1 and truncation mutants that include only one of its GEF activities on the morphology of PC12 phaeochromocytoma cells. Ras-GRF1 required coexpression of H-Ras to induce morphological effects. Ras-GRF1 plus H-Ras induced a novel, expanded morphology in PC12 cells, which was characterized by a 10-fold increase...
100.
Akt Binds to and Phosphorylates Phospholipase C-?1 in Response to Epidermal Growth Factor - Wang, Yi; Wu, Jiliang; Wang, Zhixiang
Both phospholipase (PL) C-?1 and Akt (protein kinase B; PKB) are signaling proteins that play significant roles in the intracellular signaling mechanism used by receptor tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR). EGFR activates PLC-?1 directly and activates Akt indirectly through phosphatidylinositol 3-kinase (PI3K). Many studies have shown that the PLC-?1 pathway and PI3KAkt pathway interact with each other. However, it is not known whether PLC-?1 binds to Akt directly. In this communication, we identified a novel interaction between PLC-?1 and Akt. We demonstrated that the interaction is mediated by the binding of PLC-?1 Src homology (SH) 3...
81.
