This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.biosignaling.com The latest articles from Cell Communication and Signaling (ISSN 1478-811X) published by BioMed Central Thymic stromal lymphopoietin (TSLP), a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs). DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa. These different cells secrete inflammatory cytokines and chemokines operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus, involved in the control of both an innate and an adaptive immune response. Since TSLP links contact of allergen with the airway epithelium to the onset and maintainance of the asthmatic syndrome, defining the signal transduction underlying TSLP expression and function is of profound interest for a better understandimg of the disease and for the development of new therapeutics. http://www.biosignaling.com/content/6/1/5 Katrin Sebastian, Andreas Borowski, Michael Kuepper and Karlheinz Friedrich Cell Communication and Signaling 2008, 6:5 2008-08-25 doi:10.1186/1478-811X-6-5 Cell Communication and Signaling 1478-811X 6 5 2008-08-25 The concept of a pre-emptive strike as a good means to prevent greater harm may be frequently over-stressed in daily life. However, biological systems in a homeostatic balance are prepared to withstand a certain degree of hostile fire by rather passive means. This also applies to the maintenance of cell survival, where a plethora of protective proteins provide safeguard against erroneous activation of death pathways. Apart from these mechanisms active processes are also essential for the maintenance of cellular homeostasis, commonly referred to as survival signaling. Frequently their targets may be mitochondrial, assuring organelle integrity, which is essential for continued energy production and survival. Transient or permanent failures in these cellular defense strategies result in pathophysiological conditions, which manifest themselves e.g. as cancer or ischemia/reperfusion-associated organ damage. http://www.biosignaling.com/content/6/1/4 Martin Hermann, Andrey Kuznetsov, Manuel Maglione, Julija Smigelskaite, Raimund Margreiter and Jakob Troppmair Cell Communication and Signaling 2008, 6:4 2008-08-19 doi:10.1186/1478-811X-6-4 Cell Communication and Signaling 1478-811X 6 4 2008-08-19 Background: T cells play a central role in many inflammatory diseases, hence the identification and validation of T cell-specific target genes will increase the understanding of T cell function in pathologic inflammatory situations. RNA interference (RNAi), with its ability to induce specific gene silencing in mammalian cells, represents a powerful technology to investigate and validate the function of pharmaceutical target genes in vitro and in vivo. The aim of the present study was to systematically explore RNAi-mediated gene-silencing of known T cell-specific model signaling molecules in primary murine T cells in vitro and in vivo. Results: We demonstrate that siRNA delivery and subsequent silencing of T cell specific genes is substantially increased, if murine T cells were activated prior siRNA transfection. Silencing of ZAP70, p56Lck as well as PLC-γ1 protein expression resulted in impaired function of T cells in vitro. Furthermore, delayed type hypersensitivity (DTH) was ameliorated in vivo after adoptive transfer of ZAP70-silenced T cells.CoclusionThe combination of RNAi-mediated gene silencing and adoptive transfer of gene-silenced T cells, thus, may allow the identification and analysis of T cell-specific targets for therapeutic intervention. Additionally, this model system may represent an alternative to conventional time consuming and cost intensive gene targeting approaches. http://www.biosignaling.com/content/6/1/3 Tatjana C Gust, Luisa Neubrandt, Claudia Merz, Khusru Asadullah, Ulrich Zügel and Arne von Bonin Cell Communication and Signaling 2008, 6:3 2008-08-06 doi:10.1186/1478-811X-6-3 Cell Communication and Signaling 1478-811X 6 3 2008-08-06 Highly dynamic integrin-based focal adhesions provide an important structural basis for anchoring the cellular actin cytoskeleton to the surrounding extracellular matrix. The human pathogen Helicobacter pylori (H. pylori) directly targets integrins with drastic consequences on the epithelial cell morphology and migration, which might contribute to the disruption of the gastric epithelium in vivo. In this review, we summarize the recent findings concerning the complex mechanism through which H. pylori interferes with host integrin signaling thereby deregulating focal adhesions and the actin cytoskeleton of motile epithelial cells. http://www.biosignaling.com/content/6/1/2 Sabine Schneider, Christiane Weydig and Silja Wessler Cell Communication and Signaling 2008, 6:2 2008-08-06 doi:10.1186/1478-811X-6-2 Cell Communication and Signaling 1478-811X 6 2 2008-08-06 None http://www.biosignaling.com/content/6/1/1 Stephan M Feller, Ralf Hass, Ottmar Janssen and Karlheinz Friedrich Cell Communication and Signaling 2008, 6:1 2008-08-06 doi:10.1186/1478-811X-6-1 Cell Communication and Signaling 1478-811X 6 1 2008-08-06 editorial http://www.biosignaling.com/content/5/1/1 Bernard Perbal Cell Communication and Signaling 2007, 5:1 2007-06-05 doi:10.1186/1478-811X-5-1 Cell Communication and Signaling 1478-811X 5 1 2007-06-05 Background: Paxillin acts as an adaptor protein that localizes to focal adhesion. This protein is regulated during cell migration by phosphorylation on tyrosine, serine and threonine residues. Most of these phosphorylations have been implicated in the regulation of different steps of cell migration. The two major phosphorylation sites of paxillin in response to adhesion to an extracellular matrix are serines 188 and 190. However, the function of this phosphorylation event remains unknown. The purpose of this work was to determine the role of paxillin phosphorylation on residues S188 and S190 in the regulation of cell migration. Results: We used NBT-II epithelial cells that can be induced to migrate when plated on collagen. To examine the role of paxillin serines 188/190 in cell migration, we constructed an EGFP-tagged paxillin mutant in which S188/S190 were mutated into unphosphorylatable alanine residues. We provide evidence that paxillin is regulated by proteasomal degradation following polyubiquitylation of the protein. During active cell migration on collagen, paxillin is protected from proteasome-dependent degradation. We demonstrate that phosphorylation of serines 188/190 is necessary for the protective effect of collagen. In an effort to understand the physiological relevance of paxillin protection from degradation, we show that cells expressing the paxillin S188/190A interfering mutant spread less, have reduced protrusive activity but migrate more actively. Conclusion: Our data demonstrate for the first time that serine-regulated degradation of paxillin plays a key role in the modulation of membrane dynamics and consequently, in the control of cell motility. http://www.biosignaling.com/content/4/1/8 Nancy Abou Zeid, Ana-Maria Vallés and Brigitte Boyer Cell Communication and Signaling 2006, 4:8 2006-11-22 doi:10.1186/1478-811X-4-8 Cell Communication and Signaling 1478-811X 4 8 2006-11-22 Secreted factors and cell surface receptors can be internalized by endocytosis and translocated to the cytoplasm. Instead of being recycled or proteolysed, they sometimes translocate to the nucleus. Nuclear import generally involves a nuclear localization signal contained either in the secreted factor or its transmembrane receptor, that is recognized by the importins machinery. In the nucleus, these molecules regulate transcription of specific target genes by direct binding to transcription factors or general coregulators. In addition to the transcription regulation, nuclear secreted proteins and receptors seem to be involved in other important processes for cell life and cellular integrity such as DNA replication, DNA repair and RNA metabolism.Nuclear secreted proteins and transmembrane receptors now appear to induce new signaling pathways to regulate cell proliferation and differentiation. Their nuclear localization is often transient, appearing only during certain phases of the cell cycle. Nuclear secreted and transmembrane molecules regulate the proliferation and differentiation of a large panel of cell types during embryogenesis and adulthood and are also potentially involved in wound healing. Secreted factors such as CCN proteins, EGF, FGFs and their receptors are often detected in the nucleus of cancer cells. Nuclear localization of these molecules has been correlated with tumor progression and poor prognosis for patient survival. Nuclear growth factors and receptors may be responsible for resistance to radiotherapy. http://www.biosignaling.com/content/4/1/7 Nathalie Planque Cell Communication and Signaling 2006, 4:7 2006-10-18 doi:10.1186/1478-811X-4-7 Cell Communication and Signaling 1478-811X 4 7 2006-10-18 The identification of potential partners for CCN3(NOV) sheds new light on the biological activity of this signaling protein. In particular, the physical interaction of CCN3 with the IL33 cytokine combined with previous data indicating that CCN3 expression was regulated by TNFalpha and IL1 cytokines, point to CCN3 as a potent player in a variety of inflammatory responses, including neurodegenerative disease, and arthritis. Nuclear proteins that are involved in the regulation of RNA processing and chromatin remodeling were also found to interact with CCN3. These observations reinforce the concept that routing of CCN3 to the cell nucleus where it acts as a transcription regulator, might constitute a key element in the balance between the anti- and pro-proliferative activities of CCN3 proteins. http://www.biosignaling.com/content/4/1/6 Bernard Perbal Cell Communication and Signaling 2006, 4:6 2006-08-08 doi:10.1186/1478-811X-4-6 Cell Communication and Signaling 1478-811X 4 6 2006-08-08 Background: Vav proteins are guanine nucleotide exchange factors (GEF) for Rho family GTPases and are activated following engagement of membrane receptors. Overexpression of Vav proteins enhances lamellipodium and ruffle formation, migration, and cell spreading, and augments activation of many downstream signaling proteins like Rac, ERK and Akt. Vav proteins are composed of multiple structural domains that mediate their GEF function and binding interactions with many cellular proteins. In this report we examine the mechanisms responsible for stimulation of cell migration by an activated variant of Vav1 and identify the domains of Vav1 required for this activity. Results: We found that expression of an active form of Vav1, Vav1Y3F, in MCF-10A mammary epithelial cells increases cell migration in the absence or presence of EGF. Vav1Y3F was also able to drive Rac1 activation and PAK and ERK phosphorylation in MCF-10A cells in the absence of EGF stimulation. Mutations in the Dbl homology, pleckstrin homology, or cysteine-rich domains of Vav1Y3F abolished Rac1 or ERK activation in the absence of EGF and blocked the migration-promoting activity of Vav1Y3F. In contrast, mutations in the SH2 and C-SH3 domains did not affect Rac activation by Vav1Y3F, but reduced the ability of Vav1Y3F to induce EGF-independent migration and constitutive ERK phosphorylation. EGF-independent migration of MCF-10A cells expressing Vav1Y3F was abolished by treatment of cells with an antibody that prevents ligand binding to the EGF receptor. In addition, conditioned media collected from Vav1Y3F expressing cells stimulated migration of parental MCF-10A cells. Lastly, treatment of cells with the EGF receptor inhibitory antibody blocked the Vav1Y3F-induced, EGF-independent stimulation of ERK phosphorylation, but had no effect on Rac1 activation or PAK phosphorylation. Conclusion: Our results indicate that increased migration of active Vav1 expressing cells is dependent on Vav1 GEF activity and secretion of an EGF receptor ligand. In addition, activation of ERK downstream of Vav1 is dependent on autocrine EGF receptor stimulation while active Vav1 can stimulate Rac1 and PAK activation independent of ligand binding to the EGF receptor. Thus, stimulation of migration by activated Vav1 involves both EGF receptor-dependent and independent activities induced through the Rho GEF domain of Vav1. http://www.biosignaling.com/content/4/1/5 Julie L Wilsbacher, Sheri L Moores and Joan S Brugge Cell Communication and Signaling 2006, 4:5 2006-05-18 doi:10.1186/1478-811X-4-5 Cell Communication and Signaling 1478-811X 4 5 2006-05-18