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Science Signaling

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https://www.readbyqxmd.com/read/28325822/structural-basis-for-chemokine-recognition-by-a-g-protein-coupled-receptor-and-implications-for-receptor-activation
#1
Joshua J Ziarek, Andrew B Kleist, Nir London, Barak Raveh, Nicolas Montpas, Julien Bonneterre, Geneviève St-Onge, Crystal J DiCosmo-Ponticello, Chad A Koplinski, Ishan Roy, Bryan Stephens, Sylvia Thelen, Christopher T Veldkamp, Frederick D Coffman, Marion C Cohen, Michael B Dwinell, Marcus Thelen, Francis C Peterson, Nikolaus Heveker, Brian F Volkman
Chemokines orchestrate cell migration for development, immune surveillance, and disease by binding to cell surface heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The array of interactions between the nearly 50 chemokines and their 20 GPCR targets generates an extensive signaling network to which promiscuity and biased agonism add further complexity. The receptor CXCR4 recognizes both monomeric and dimeric forms of the chemokine CXCL12, which is a distinct example of ligand bias in the chemokine family...
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325821/phosphorylation-of-the-exocyst-protein-exo84-by-tbk1-promotes-insulin-stimulated-glut4-trafficking
#2
Maeran Uhm, Merlijn Bazuine, Peng Zhao, Shian-Huey Chiang, Tingting Xiong, Sheelarani Karunanithi, Louise Chang, Alan R Saltiel
Insulin stimulates glucose uptake through the translocation of the glucose transporter GLUT4 to the plasma membrane. The exocyst complex tethers GLUT4-containing vesicles to the plasma membrane, a process that requires the binding of the G protein (heterotrimeric guanine nucleotide-binding protein) RalA to the exocyst complex. We report that upon activation of RalA, the protein kinase TBK1 phosphorylated the exocyst subunit Exo84. Knockdown of TBK1 blocked insulin-stimulated glucose uptake and GLUT4 translocation; knockout of TBK1 in adipocytes blocked insulin-stimulated glucose uptake; and ectopic overexpression of a kinase-inactive mutant of TBK1 reduced insulin-stimulated glucose uptake in 3T3-L1 adipocytes...
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325820/autophagy-and-vitamin-d
#3
Alexandra A Mushegian
Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325819/new-connections-getting-the-good-without-the-bad-opiate-edition
#4
Wei Wong
Researchers identify strategies to limit the adverse effects and liabilities of opioid receptor-targeting drugs.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325818/paper-of-note-in-science-translational-medicine9-381
#5
Leslie K Ferrarelli
This week's article describes a therapy that may enable macrophages to recognize and kill tumor cells in pediatric patients with brain cancer.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325817/papers-of-note-in-nature543-7645
#6
Annalisa M VanHook
This week's articles highlight a function for disordered protein domains, how fish sense electric fields, the subcellular localization of nutrient sensing, metabolism in intestinal stem cells, the bone as an endocrine organ, signaling pathways that are dysregulated in cervical cancer, and a drug that stimulates the recruitment of antitumor macrophages.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325816/papers-of-note-in-science355-6330
#7
Annalisa M VanHook
This week's articles include several reviews on targeting signaling pathways to treat cancer, as well as research articles that highlight proteins that drive circadian clocks; how bacteriophages affect the virulence of pathogenic bacteria; a mobile transcription factor in plants; a secreted nucleoside that affects metabolism; and the effects of protein aggregation in aging yeast cells.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325815/neuropathic-pain-promotes-adaptive-changes-in-gene-expression-in-brain-networks-involved-in-stress-and-depression
#8
Giannina Descalzi, Vasiliki Mitsi, Immanuel Purushothaman, Sevasti Gaspari, Kleopatra Avrampou, Yong-Hwee Eddie Loh, Li Shen, Venetia Zachariou
Neuropathic pain is a complex chronic condition characterized by various sensory, cognitive, and affective symptoms. A large percentage of patients with neuropathic pain are also afflicted with depression and anxiety disorders, a pattern that is also seen in animal models. Furthermore, clinical and preclinical studies indicate that chronic pain corresponds with adaptations in several brain networks involved in mood, motivation, and reward. Chronic stress is also a major risk factor for depression. We investigated whether chronic pain and stress affect similar molecular mechanisms and whether chronic pain can affect gene expression patterns that are involved in depression...
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292960/degrons-in-cancer
#9
REVIEW
Bálint Mészáros, Manjeet Kumar, Toby J Gibson, Bora Uyar, Zsuzsanna Dosztányi
Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the cell cycle and monitoring cellular hypoxia. Degrons enable the elimination of proteins that are no longer required, preventing their possible dysfunction. Although the human genome encodes ~600 E3 ubiquitin ligases, only a fraction of these enzymes have well-defined target degrons...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292959/multiepitope-tissue-analysis-reveals-sppl3-mediated-adam10-activation-as-a-key-step-in-the-transformation-of-melanocytes
#10
Christian Ostalecki, Jung-Hyun Lee, Jochen Dindorf, Lena Collenburg, Stephan Schierer, Beate Simon, Stefan Schliep, Elisabeth Kremmer, Gerold Schuler, Andreas S Baur
The evolution of cancer is characterized by the appearance of specific mutations, but these mutations are translated into proteins that must cooperate to induce malignant transformation. Using a systemic approach with the multiepitope ligand cartography (MELC) technology, we analyzed protein expression profiles (PEPs) in nevi and BRAF(V600E)-positive superficial spreading melanomas (SSMs) from patient tissues to identify key transformation events. The PEPs in nevi and SSMs differed predominantly in the abundance of specific antigens, but the PEPs of nevi- and melanoma-associated keratinocytes gradually changed during the transformation process...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292958/molecular-mechanisms-and-therapeutic-targets-in-pediatric-brain-tumors
#11
REVIEW
Kun-Wei Liu, Kristian W Pajtler, Barbara C Worst, Stefan M Pfister, Robert J Wechsler-Reya
Brain tumors are among the leading causes of cancer-related deaths in children. Although surgery, aggressive radiation, and chemotherapy have improved outcomes, many patients still die of their disease. Moreover, those who survive often suffer devastating long-term side effects from the therapies. A greater understanding of the molecular underpinnings of these diseases will drive the development of new therapeutic approaches. Advances in genomics and epigenomics have provided unprecedented insight into the molecular diversity of these diseases and, in several cases, have revealed key genes and signaling pathways that drive tumor growth...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292957/psma-redirects-cell-survival-signaling-from-the-mapk-to-the-pi3k-akt-pathways-to-promote-the-progression-of-prostate-cancer
#12
Leslie Ann Caromile, Kristina Dortche, M Mamunur Rahman, Christina L Grant, Christopher Stoddard, Fernando A Ferrer, Linda H Shapiro
Increased abundance of the prostate-specific membrane antigen (PSMA) on prostate epithelium is a hallmark of advanced metastatic prostate cancer (PCa) and correlates negatively with prognosis. However, direct evidence that PSMA functionally contributes to PCa progression remains elusive. We generated mice bearing PSMA-positive or PSMA-negative PCa by crossing PSMA-deficient mice with transgenic PCa (TRAMP) models, enabling direct assessment of PCa incidence and progression in the presence or absence of PSMA...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292956/endoplasmic-reticulum-proteostasis-in-glioblastoma-from-molecular-mechanisms-to-therapeutic-perspectives
#13
REVIEW
Joanna Obacz, Tony Avril, Pierre-Jean Le Reste, Hery Urra, Véronique Quillien, Claudio Hetz, Eric Chevet
Cellular stress induced by the accumulation of misfolded proteins at the endoplasmic reticulum (ER) is a central feature of secretory cells and is observed in many tissues in various diseases, including cancer, diabetes, obesity, and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the cytosol and nucleus to restore proteostasis...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292955/strem2-and-neuroinflammation
#14
John F Foley
The soluble form of the innate immune receptor TREM2 promotes microglial survival and inflammatory responses in the brain.
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292954/an-insulin-like-message-from-mother
#15
Alexandra A Mushegian
Nematodes experiencing osmotic stress signal to the germ-line to prepare their offspring.
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292953/science-signaling-podcast-for-14-march-2017-the-cancer-moonshot
#16
Michael B Yaffe, Annalisa M VanHook
This Podcast features a conversation with Science Signaling's Chief Scientific Editor Michael Yaffe about opportunities for signaling researchers to contribute to the Cancer Moonshot, a federally funded initiative to accelerate cancer research. Administered by the National Cancer Institute (NCI), the goal of the program is to improve the prevention, diagnosis, and treatment of cancer. Signaling pathways are not only critical for the initiation and progression of cancer; they are also critical targets for treatment...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292952/hypothermia-induced-neuroprotection
#17
Annalisa M VanHook
A reticulon contributes to the neuroprotective effects of hypothermia.
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292951/papers-of-note-in-science-translational-medicine9-380
#18
Leslie K Ferrarelli
This week's articles describe an antibody that inhibits two pathways that drive lung cancer and a new way to lessen colitis in Crohn's disease.
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292950/papers-of-note-in-nature543-7644
#19
Annalisa M VanHook
This week's articles highlight the role of autophagy in maintaining stem cells and a new player in the repair of double-strand DNA breaks.
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292949/papers-of-note-in-science355-6329
#20
Annalisa M VanHook
This week's articles describe the molecules and neural circuit that mediate contagious itch and an isoprenoid released by Plasmodium that enhances the transmission of this parasite through multiple mechanisms.
March 14, 2017: Science Signaling
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