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Science Signaling

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https://www.readbyqxmd.com/read/29789297/the-duf1669-domain-of-fam83-family-proteins-anchor-casein-kinase-1-isoforms
#1
Luke J Fulcher, Polyxeni Bozatzi, Theresa Tachie-Menson, Kevin Z L Wu, Timothy D Cummins, Joshua C Bufton, Daniel M Pinkas, Karen Dunbar, Sabin Shrestha, Nicola T Wood, Simone Weidlich, Thomas J Macartney, Joby Varghese, Robert Gourlay, David G Campbell, Kevin S Dingwell, James C Smith, Alex N Bullock, Gopal P Sapkota
Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29789296/tuning-itam-multiplicity-on-t-cell-receptors-can-control-potency-and-selectivity-to-ligand-density
#2
John R James
The T cell antigen receptor (TCR) recognizes peptides from pathogenic proteins bound in the major histocompatibility complex (MHC). To convert this binding event into downstream signaling, the TCR complex contains immunoreceptor tyrosine-based activation motifs (ITAMs) that act as docking sites for the cytoplasmic tyrosine kinase ZAP-70. Unique among antigen receptors, the TCR complex uses 10 ITAMs to transduce peptide-MHC binding to the cell interior. Using synthetic, drug-inducible receptor-ligand pairs, it was found that greater ITAM multiplicity primarily enhanced the efficiency with which ligand binding was converted into an intracellular signal...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29789295/integration-of-protein-phosphorylation-acetylation-and-methylation-data-sets-to-outline-lung-cancer-signaling-networks
#3
Mark Grimes, Benjamin Hall, Lauren Foltz, Tyler Levy, Klarisa Rikova, Jeremiah Gaiser, William Cook, Ekaterina Smirnova, Travis Wheeler, Neil R Clark, Alexander Lachmann, Bin Zhang, Peter Hornbeck, Avi Ma'ayan, Michael Comb
Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29764992/aurora-b-opposes-pp1-function-in-mitosis-by-phosphorylating-the-conserved-pp1-binding-rvxf-motif-in-pp1-regulatory-proteins
#4
Isha Nasa, Scott F Rusin, Arminja N Kettenbach, Greg B Moorhead
Protein phosphatase 1 (PP1) is a highly conserved protein phosphatase that performs most of the serine- and threonine-dephosphorylation reactions in eukaryotes and opposes the actions of a diverse set of serine and threonine (Ser-Thr) protein kinases. PP1 gains substrate specificity through binding to a large number (>200) of regulatory proteins that control PP1 localization, activity, and interactions with substrates. PP1 recognizes the well-characterized RVxF binding motif that is present in many of these regulatory proteins, thus generating a multitude of distinct PP1 holoenzymes...
May 15, 2018: Science Signaling
https://www.readbyqxmd.com/read/29764991/a-dgk%C3%AE-foxo-ubiquitin-proteolytic-axis-controls-fiber-size-during-skeletal-muscle-remodeling
#5
Jae-Sung You, Matthew S Dooley, Chan-Ran Kim, Eui-Jun Kim, Wei Xu, Craig A Goodman, Troy A Hornberger
Skeletal muscle rapidly remodels in response to various stresses, and the resulting changes in muscle mass profoundly influence our health and quality of life. We identified a diacylglycerol kinase ζ (DGKζ)-mediated pathway that regulated muscle mass during remodeling. During mechanical overload, DGKζ abundance was increased and required for effective hypertrophy. DGKζ not only augmented anabolic responses but also suppressed ubiquitin-proteasome system (UPS)-dependent proteolysis. We found that DGKζ inhibited the transcription factor FoxO that promotes the induction of the UPS...
May 15, 2018: Science Signaling
https://www.readbyqxmd.com/read/29764990/ire1%C3%AE-prevents-hepatic-steatosis-by-processing-and-promoting-the-degradation-of-select-micrornas
#6
Jie-Mei Wang, Yining Qiu, Zhao Yang, Hyunbae Kim, Qingwen Qian, Qinghua Sun, Chunbin Zhang, Lei Yin, Deyu Fang, Sung Hong Back, Randal J Kaufman, Ling Yang, Kezhong Zhang
Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is caused by lipid accumulation in the liver. We found that IRE1α was critical to maintaining lipid homeostasis in the liver by repressing the biogenesis of microRNAs (miRNAs) that regulate lipid mobilization...
May 15, 2018: Science Signaling
https://www.readbyqxmd.com/read/29764989/global-assessment-of-its-network-dynamics-reveals-that-the-kinase-plk1-inhibits-the-phosphatase-pp6-to-promote-aurora-a-activity
#7
Arminja N Kettenbach, Kate A Schlosser, Scott P Lyons, Isha Nasa, Jiang Gui, Mark E Adamo, Scott A Gerber
Polo-like kinase 1 (Plk1) is an essential protein kinase that promotes faithful mitotic progression in eukaryotes. The subcellular localization and substrate interactions of Plk1 are tightly controlled and require its binding to phosphorylated residues. To identify phosphorylation-dependent interactions within the Plk1 network in human mitotic cells, we performed quantitative proteomics on HeLa cells cultured with kinase inhibitors or expressing a Plk1 mutant that was deficient in phosphorylation-dependent substrate binding...
May 15, 2018: Science Signaling
https://www.readbyqxmd.com/read/29739882/gene-expression-kinetics-governs-stimulus-specific-decoration-of-the-salmonella-outer-membrane
#8
Xinyu Hong, H Deborah Chen, Eduardo A Groisman
Lipid A is the innermost component of the lipopolysaccharide (LPS) molecules that occupy the outer leaflet of the outer membrane in Gram-negative bacteria. Lipid A is recognized by the host immune system and targeted by cationic antimicrobial compounds. In Salmonella enterica serovar Typhimurium, the phosphates of lipid A are chemically modified by enzymes encoded by targets of the transcriptional regulator PmrA. These modifications increase resistance to the cationic peptide antibiotic polymyxin B by reducing the negative charge of the LPS...
May 8, 2018: Science Signaling
https://www.readbyqxmd.com/read/29739881/the-receptor-tyrosine-kinase-trkb-signals-without-dimerization-at-the-plasma-membrane
#9
Eitan Erez Zahavi, Noam Steinberg, Topaz Altman, Michael Chein, Yuvraj Joshi, Tal Gradus-Pery, Eran Perlson
Tropomyosin-related tyrosine kinase B (TrkB) is the receptor for brain-derived neurotrophic factor (BDNF) and provides critical signaling that supports the development and function of the mammalian nervous system. Like other receptor tyrosine kinases (RTKs), TrkB is thought to signal as a dimer. Using cell imaging and biochemical assays, we found that TrkB acted as a monomeric receptor at the plasma membrane regardless of its binding to BDNF and initial activation. Dimerization occurred only after the internalization and accumulation of TrkB monomers within BDNF-containing endosomes...
May 8, 2018: Science Signaling
https://www.readbyqxmd.com/read/29739880/ccr5-adopts-three-homodimeric-conformations-that-control-cell-surface-delivery
#10
Jun Jin, Fanny Momboisse, Gaelle Boncompain, Florian Koensgen, Zhicheng Zhou, Nelia Cordeiro, Fernando Arenzana-Seisdedos, Franck Perez, Bernard Lagane, Esther Kellenberger, Anne Brelot
Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization interfaces of the chemokine receptor CCR5, the major co-receptor for HIV-1 entry into cells. We provide evidence of three distinct CCR5 dimeric organizations, involving residues of transmembrane helix 5...
May 8, 2018: Science Signaling
https://www.readbyqxmd.com/read/29739879/chemical-synapses-without-synaptic-vesicles-purinergic-neurotransmission-through-a-calhm1-channel-mitochondrial-signaling-complex
#11
Roman A Romanov, Robert S Lasher, Brigit High, Logan E Savidge, Adam Lawson, Olga A Rogachevskaja, Haitian Zhao, Vadim V Rogachevsky, Marina F Bystrova, Gleb D Churbanov, Igor Adameyko, Tibor Harkany, Ruibiao Yang, Grahame J Kidd, Philippe Marambaud, John C Kinnamon, Stanislav S Kolesnikov, Thomas E Finger
Conventional chemical synapses in the nervous system involve a presynaptic accumulation of neurotransmitter-containing vesicles, which fuse with the plasma membrane to release neurotransmitters that activate postsynaptic receptors. In taste buds, type II receptor cells do not have conventional synaptic features but nonetheless show regulated release of their afferent neurotransmitter, ATP, through a large-pore, voltage-gated channel, CALHM1. Immunohistochemistry revealed that CALHM1 was localized to points of contact between the receptor cells and sensory nerve fibers...
May 8, 2018: Science Signaling
https://www.readbyqxmd.com/read/29717064/glycerol-monolaurate-induces-filopodia-formation-by-disrupting-the-association-between-lat-and-slp-76-microclusters
#12
Michael S Zhang, Phuong M Tran, Alexander J Wolff, Mikaela M Tremblay, Micaela G Fosdick, Jon C D Houtman
Glycerol monolaurate (GML) is a monoglyceride with potent antimicrobial properties that suppresses T cell receptor (TCR)-induced signaling and T cell effector function. Actin rearrangement is needed for the interaction of T cells with antigen-presenting cells and for migration to sites of infection. Because of the critical role actin rearrangement plays in T cell effector function, we analyzed the effect of GML on the rearrangement of the actin cytoskeleton after TCR activation. We found that GML-treated human T cells were less adherent than untreated T cells and did not form actin ring structures but instead developed numerous inappropriate actin-mediated filopodia...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29717063/nuclear-pten-enhances-the-maturation-of-a-microrna-regulon-to-limit-myd88-dependent-susceptibility-to-sepsis
#13
Flavia Sisti, Soujuan Wang, Stephanie L Brandt, Nicole Glosson-Byers, Lindsey D Mayo, Young Min Son, Sarah Sturgeon, Luciano Filgueiras, Sonia Jancar, Hector Wong, Charles S Dela Cruz, Nathaniel Andrews, Jose Carlos Alves-Filho, Fernando Q Cunha, C Henrique Serezani
Sepsis-induced organ damage is caused by systemic inflammatory response syndrome (SIRS), which results in substantial comorbidities. Therefore, it is of medical importance to identify molecular brakes that can be exploited to dampen inflammation and prevent the development of SIRS. We investigated the role of phosphatase and tensin homolog (PTEN) in suppressing SIRS, increasing microbial clearance, and preventing lung damage. Septic patients and mice with sepsis exhibited increased PTEN expression in leukocytes...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29717062/vegf-neuropilin-2-signaling-promotes-stem-like-traits-in-breast-cancer-cells-by-taz-mediated-repression-of-the-rac-gap-%C3%AE-2-chimaerin
#14
Ameer L Elaimy, Santosh Guru, Cheng Chang, Jianhong Ou, John J Amante, Lihua Julie Zhu, Hira Lal Goel, Arthur M Mercurio
The role of vascular endothelial growth factor (VEGF) signaling in cancer is not only well known in the context of angiogenesis but also important in the functional regulation of tumor cells. Autocrine VEGF signaling mediated by its co-receptors called neuropilins (NRPs) appears to be essential for sustaining the proliferation and survival of cancer stem cells (CSCs), which are implicated in mediating tumor growth, progression, and drug resistance. Therefore, understanding the mechanisms involved in VEGF-mediated support of CSCs is critical to successfully treating cancer patients...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29717061/the-interaction-between-ikk%C3%AE-and-lc3-promotes-type-i-interferon-production-through-the-tlr9-containing-laposome
#15
Kachiko Hayashi, Manabu Taura, Akiko Iwasaki
Toll-like receptor 9 (TLR9) recognizes DNA in endosomes and activates distinct signaling pathways to stimulate the production of proinflammatory cytokines and type I interferons (IFNs). The assembly of signaling platforms on microtubule-associated proteins 1A/1B-light chain 3 (LC3)-decorated endosomal vesicles is required to transduce TLR9 signals that stimulate the production of IFN but not interleukin-12 p40 (IL-12p40). LC3-associated phagocytosis (LAP), a form of noncanonical autophagy, is critical for the activation of interferon regulatory factor 7 (IRF7) and for IFN synthesis...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29692364/mitophagy-controls-beige-adipocyte-maintenance-through-a-parkin-dependent-and-ucp1-independent-mechanism
#16
Xiaodan Lu, Svetlana Altshuler-Keylin, Qiang Wang, Yong Chen, Carlos Henrique Sponton, Kenji Ikeda, Pema Maretich, Takeshi Yoneshiro, Shingo Kajimura
Beige adipocytes are an inducible form of mitochondria-enriched thermogenic adipocytes that emerge in response to external stimuli, such as chronic cold exposure. We have previously shown that after the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype through autophagy-mediated mitochondrial degradation. We investigated the upstream pathway that mediates mitochondrial clearance and report that Parkin-mediated mitophagy plays a key role in the beige-to-white adipocyte transition...
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29692363/jak-tgf%C3%AE-cross-talk-links-transient-adipose-tissue-inflammation-to-beige-adipogenesis
#17
Rohollah Babaei, Maximilian Schuster, Irina Meln, Sarah Lerch, Rayane A Ghandour, Didier F Pisani, Irem Bayindir-Buchhalter, Julia Marx, Shuang Wu, Gabriele Schoiswohl, Adrian T Billeter, Damir Krunic, Jan Mauer, Yun-Hee Lee, James G Granneman, Lars Fischer, Beat P Müller-Stich, Ez-Zoubir Amri, Erin E Kershaw, Mathias Heikenwälder, Stephan Herzig, Alexandros Vegiopoulos
The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as β3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFβ signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors...
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29692362/transient-inflammatory-signaling-promotes-beige-adipogenesis
#18
REVIEW
Kai Sun, Zhanguo Gao, Mikhail G Kolonin
Inflammatory signaling has been implicated in adipose tissue remodeling and metabolism. In this issue of Science Signaling , Babaei et al report that lipolysis induced by β3-adrenergic signaling triggers transient inflammation that directs progenitor cells toward beige adipogenesis.
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29692361/a-defect-in-kca3-1-channel-activity-limits-the-ability-of-cd8-t-cells-from-cancer-patients-to-infiltrate-an-adenosine-rich-microenvironment
#19
Ameet A Chimote, Andras Balajthy, Michael J Arnold, Hannah S Newton, Peter Hajdu, Julianne Qualtieri, Trisha Wise-Draper, Laura Conforti
The limited ability of cytotoxic T cells to infiltrate solid tumors hampers immune surveillance and the efficacy of immunotherapies in cancer. Adenosine accumulates in solid tumors and inhibits tumor-specific T cells. Adenosine inhibits T cell motility through the A2A receptor (A2A R) and suppression of KCa3.1 channels. We conducted three-dimensional chemotaxis experiments to elucidate the effect of adenosine on the migration of peripheral blood CD8+ T cells from head and neck squamous cell carcinoma (HNSCC) patients...
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29692360/parkin-mediates-mitophagy-during-beige-to-white-fat-conversion
#20
REVIEW
Shireen A Sarraf, Richard J Youle
In this issue of Science Signaling , Lu et al reveal a role for Parkin-mediated mitophagy in beige-to-white adipocyte transition. In the absence of Parkin, mitochondria in thermogenic beige adipocytes are preserved even after the elimination of cold mimetic stimuli-in contrast to their typical elimination during the white transition.
April 24, 2018: Science Signaling
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