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Berlin Brandenburg

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  • Signal Transduction
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  • 1
    Language: English
    In: Cell, 1997, Vol.91(5), pp.605-615
    Description: Invasion of human mucosal cells by N. gonorrhoeae via the binding to heparansulfate proteoglycan receptors is considered a crucial event of the infection. Using different human epithelial cells and primary fibroblasts, we show here an activation of the phosphatidylcholine-specific phospholipase C (PC-PLC) and acidic sphingomyelinase (ASM) by N. gonorrhoeae, resulting in the release of diacylglycerol and ceramide. Genetic and/or pharmacological blockade of ASM and PC-PLC cause inhibition of cellular invasion by N. gonorrhoeae. Complementation of ASM-deficient fibroblasts from Niemann-Pick disease patients restored N. gonorrhoeae-induced signaling and entry processes. The activation of PC-PLC and ASM, therefore, is an essential requirement for the entry of N. gonorrhoeae into distinct nonphagocytic human cell types including several epithelial cells and primary fibroblasts.
    Keywords: Biology
    ISSN: 0092-8674
    E-ISSN: 1097-4172
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  • 2
    Language: English
    In: Nature Communications, 01 May 2018, Vol.9(1), pp.1-15
    Description: Cytokine-induced signaling acts as an ON/OFF switch dependent on the presence of ligands. Here the authors construct synthetic cytokine receptors responsive to synthetic ligands able to activate canonical signaling pathways.
    Keywords: Biology
    E-ISSN: 2041-1723
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  • 3
    Language: English
    In: Journal of Biological Chemistry, 10/18/1996, Vol.271(42), pp.26389-26394
    Description: Fas induces apoptosis in lymphocytes via a poorly defined intracellular signaling mechanism. We and others have previously demonstrated the involvement and significance of a signaling cascade from the Fas receptor via sphingomyelinases and ceramide to Ras in apoptosis (Gulbins, E., Bissonette, R., Mahboubi, A., Nishioka, W., Brunner, T., Baier G., Baier-Bitterlich, G., Byrd, C., Lang, F., Kolesnick, R., Altman, A., and Green, D. (1995) Immunity 2, 341; Cifone, M. G., DeMaria, R., Roncali, P., Rippo, M. R., Azuma, M., Lanier, L. L., Santoni, A., and Testi, R. (1994) J. Exp. Med. 180, 1547-1552; Gill, B. M., Nishikata, H., Chan, G., Delovitch, T. L., and Ochi, A. (1994) Immunol. Rev. 142, 113-126). Here, we demonstrate an activation of the small G-proteins Rac 1 and Rac 2 after Fas receptor triggering. Expression of a transdominant inhibitory Ras mutant (N17Ras) prevents Rac 1 and Rac 2 stimulation, suggesting a signaling cascade from the Fas receptor via Ras to Rac 1 and Rac 2. Genetic and pharmacological inhibition of Ras or Rac 1 and Rac 2 stimulation blocks Fas-induced apoptosis, pointing to an important function of a Ras and Rac protein-regulated signaling pathway in Fas-mediated programmed cell death.
    Keywords: Chemistry ; Anatomy & Physiology;
    ISSN: 0021-9258
    E-ISSN: 1083-351X
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  • 4
    Language: English
    In: Journal of neurotrauma, 15 November 2018, Vol.35(22), pp.2718-2735
    Description: Ethanol intoxication (EI) is a frequent comorbidity of traumatic brain injury (TBI), but the impact of EI on TBI pathogenic cascades and prognosis is unclear. Although clinical evidence suggests that EI may have neuroprotective effects, experimental support is, to date, inconclusive. We aimed at elucidating the impact of EI on TBI-associated neurological deficits, signaling pathways, and pathogenic cascades in order to identify new modifiers of TBI pathophysiology. We have shown that ethanol administration (5 g/kg) before trauma enhances behavioral recovery in a weight-drop TBI model. Neuronal survival in the injured somatosensory cortex was also enhanced by EI. We have used phospho-receptor tyrosine kinase (RTK) arrays to screen the impact of ethanol on TBI-induced activation of RTK in somatosensory cortex, identifying ErbB2/ErbB3 among the RTKs activated by TBI and suppressed by ethanol. Phosphorylation of ErbB2/3/4 RTKs were upregulated in vGlut2 excitatory synapses in the injured cortex, including excitatory synapses located on parvalbumin (PV)-positive interneurons. Administration of selective ErbB inhibitors was able to recapitulate, to a significant extent, the neuroprotective effects of ethanol both in sensorimotor performance and structural integrity. Further, suppression of PV interneurons in somatosensory cortex before TBI, by engineered receptors with orthogonal pharmacology, could mimic the beneficial effects of ErbB inhibitors. Thus, we have shown that EI interferes with TBI-induced pathogenic cascades at multiple levels, with one prominent pathway, involving ErbB-dependent modulation of PV interneurons.
    Keywords: Chemogenetics ; Ethanol Intoxication ; Inhibitory Interneurons ; Traumatic Brain Injury ; Tyrosine Kinase Receptors
    ISSN: 08977151
    E-ISSN: 1557-9042
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  • 5
    Language: English
    In: FEBS Letters, 1997, Vol.417(3), pp.301-306
    Description: The interaction of the CD40 receptor with its ligand has been shown to be crucial for the activation of B-lymphocytes. Here, we provide evidence that the pg39 molecule/CD40 ligand (gp39/CD40L) also functions as a stimulatory molecule for T-lymphocytes. Activation of T-lymphocytes via gp39/CD40L induced a strong activation of Jun-N-terminal kinase (JNK) and p38-K. Activation of these kinases correlates with a stimulation of Rac1 and inhibition of Rac1 prevents gp39/CD40L triggered JNK/p38-K activation. Further, cellular stimulation via the CD40 ligand results in tyrosine phosphorylation of cellular proteins and the activation of p56(lck). Inhibition of src-like kinases inhibits Rac1 as well as JNK/p38-K stimulation suggesting a signalling cascade from the gp39/CD40L via p56(lck) and Rac1 to JNK/p38-K.
    Keywords: Cd40 Ligand ; Gp39 ; T-Lymphocytes ; Tyrosine Kinase ; Jun-N-Terminal Kinase ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0014-5793
    E-ISSN: 1873-3468
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  • 6
    Language: English
    In: Science (New York, N.Y.), 04 January 2008, Vol.319(5859), pp.64-9
    Description: We report the draft genome sequence of the model moss Physcomitrella patens and compare its features with those of flowering plants, from which it is separated by more than 400 million years, and unicellular aquatic algae. This comparison reveals genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments (e.g., flagellar arms); acquisition of genes for tolerating terrestrial stresses (e.g., variation in temperature and water availability); and the development of the auxin and abscisic acid signaling pathways for coordinating multicellular growth and dehydration response. The Physcomitrella genome provides a resource for phylogenetic inferences about gene function and for experimental analysis of plant processes through this plant's unique facility for reverse genetics.
    Keywords: Biological Evolution ; Genome, Plant ; Bryopsida -- Genetics
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 7
    Language: English
    In: Cellular Signalling, 1999, Vol.11(4), pp.301-308
    Description: Leucocyte adhesion to endothelial cells is a tightly regulated process involving selectins, integrins and immunoglobulin-like proteins. Cell adhesion and communication are controlled by membrane dynamics like receptor capping. Capping of surface receptors is an ubiquitous mechanism but still not well understood. Employing immunofluorescence techniques, we demonstrate that l -selectin triggering results in receptor capping of the l -selectin molecules in lymphocytes. Using pharmacological inhibitors and genetic deficient cell lines we show that this process involves intracellular signalling molecules. l -Selectin capping seems to be independent on activation of p56 lck -kinase, but requires the neutral sphingomyelinase, small G proteins and the cytoskeleton. Therefore, capping of l -selectin upon stimulation might play an important role in the very early phase of lymphocyte trafficking.
    Keywords: L-Selectin ; Adhesion ; Capping ; Signal Transduction ; Lymphocytes ; Neutral Sphingomyelinase ; Biology
    ISSN: 0898-6568
    E-ISSN: 1873-3913
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