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Foxo1 and Foxp1 play opposing roles in regulating the differentiation and antitumor activity of TH9 cells programmed by IL-7
Tumor-specific CD4+ T helper 9 (TH9) cells, so-called because of their production of the cytokine interleukin-9 (IL-9), are a powerful effector T cell subset for cancer immunotherapy. We found that pretreatment of naìˆve CD4+ T cells with IL-7 further enhanced their differentiation into TH9 cells and augmented their antitumor activity. IL-7 markedly increased the abundance of the histone acetyltransferase p300 by activating the STAT5 and PI3K-AKT-mTOR signaling pathways and promoting the acetylation of histones at the Il9 promoter. As a result, the transcriptional regulator Foxo1 was dephosphorylated and translocated to t...
Source: Signal Transduction Knowledge Environment - October 10, 2017 Category: Science Authors: Bi, E., Ma, X., Lu, Y., Yang, M., Wang, Q., Xue, G., Qian, J., Wang, S., Yi, Q. Tags: STKE Research Articles Source Type: news

Dual enhancement of T and NK cell function by pulsatile inhibition of SHIP1 improves antitumor immunity and survival
The success of immunotherapy in some cancer patients has revealed the profound capacity for cytotoxic lymphocytes to eradicate malignancies. Various immunotherapies work by blocking key checkpoint proteins that suppress immune cell activity. The phosphatase SHIP1 (SH2-containing inositol polyphosphate 5-phosphatase) limits signaling from receptors that activate natural killer (NK) cells and T cells. However, unexpectedly, genetic ablation studies have shown that the effector functions of SHIP1-deficient NK and T cells are compromised in vivo. Because chronic activation of immune cells renders them less responsive to activa...
Source: Signal Transduction Knowledge Environment - October 10, 2017 Category: Science Authors: Gumbleton, M., Sudan, R., Fernandes, S., Engelman, R. W., Russo, C. M., Chisholm, J. D., Kerr, W. G. Tags: STKE Research Articles Source Type: news

Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects
We report that two heat-activated transient receptor potential (TRP) ion channels, TRPV1 and TRPV4, were present in neural crest cells during critical windows of heart and face development. TRPV1 antagonists protected against the development of hyperthermia-induced defects in chick embryos. Treatment with chemical agonists of TRPV1 or TRPV4 replicated hyperthermia-induced birth defects in chick and zebrafish embryos. To test whether transient TRPV channel permeability in neural crest cells was sufficient to induce these defects, we engineered iron-binding modifications to TRPV1 and TRPV4 that enabled remote and noninvasive...
Source: Signal Transduction Knowledge Environment - October 10, 2017 Category: Science Authors: Hutson, M. R., Keyte, A. L., Hernandez-Morales, M., Gibbs, E., Kupchinsky, Z. A., Argyridis, I., Erwin, K. N., Pegram, K., Kneifel, M., Rosenberg, P. B., Matak, P., Xie, L., Grandl, J., Davis, E. E., Katsanis, N., Liu, C., Benner, E. J. Tags: STKE Research Articles Source Type: news

New connections: Pregnancy-specific signaling
Three papers highlight the cross-talk that occurs between mother and fetus during pregnancy. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 10, 2017 Category: Science Authors: Wong, W. Tags: STKE Editors ' Choice Source Type: news

Highlight: Antitumor strategies
Two papers highlight potential ways to boost the antitumor immune response. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 10, 2017 Category: Science Authors: Foley, J. F. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 550 (7674)
This week’s articles highlight retrograde semaphorin signaling at synapses; a driver of age-related decreases in lipolysis; and a mechanism by which melanoma cells become resistant to combined therapies. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 10, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (410)
This week’s article and a review describe ways to potentially improve immunotherapy for cancer patients. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 10, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in Ewings sarcoma
Ewing’s sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is implicated in driving most ES cases by modulation of transcription and alternative splicing. The small-molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis in ES cells. We aimed to identify both the underlying mechanism of the drug and potential combination therapies that might enhance its...
Source: Signal Transduction Knowledge Environment - October 3, 2017 Category: Science Authors: Zöllner, S. K., Selvanathan, S. P., Graham, G. T., Commins, R. M. T., Hong, S. H., Moseley, E., Parks, S., Haladyna, J. N., Erkizan, H. V., Dirksen, U., Hogarty, M. D., Üren, A., Toretsky, J. A. Tags: STKE Research Articles Source Type: news

Genome-wide functional analysis reveals central signaling regulators of lymphatic endothelial cell migration and remodeling
Lymphatic vessels constitute a specialized vasculature that is involved in development, cancer, obesity, and immune regulation. The migration of lymphatic endothelial cells (LECs) is critical for vessel growth (lymphangiogenesis) and vessel remodeling, processes that modify the lymphatic network in response to developmental or pathological demands. Using the publicly accessible results of our genome-wide siRNA screen, we characterized the migratome of primary human LECs and identified individual genes and signaling pathways that regulate LEC migration. We compared our data set with mRNA differential expression data from en...
Source: Signal Transduction Knowledge Environment - October 3, 2017 Category: Science Authors: Williams, S. P., Odell, A. F., Karnezis, T., Farnsworth, R. H., Gould, C. M., Li, J., Paquet-Fifield, S., Harris, N. C., Walter, A., Gregory, J. L., Lamont, S. F., Liu, R., Takano, E. A., Nowell, C. J., Bower, N. I., Resnick, D., Smyth, G. K., Coultas, L. Tags: STKE Research Articles Source Type: news

Papers of note in Science Immunology 2 (15)
This month’s articles highlight the adaptations in the maternal immune system during pregnancy and show how follicular regulatory T cells suppress B cell activation. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 3, 2017 Category: Science Authors: Foley, J. F. Tags: STKE Editors ' Choice Source Type: news

Pathogen-induced mitochondrial fragmentation
Legionella pneumophila promotes activation of the mitochondrial fission machinery to metabolically reprogram host macrophages. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 3, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 357 (6358)
This week’s article shows that the release of oxytocin in the ventral tegmental area influences sociability in mice by stimulating dopaminergic neurons that project to the brain’s reward center. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 3, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (409)
This week’s articles describe a stem cell–based therapy for chronic kidney disease and targets for treating diabetic nerve pain and acute respiratory distress in critically ill patients. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 3, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 549 (7673)
This week’s articles highlight the role of vitamin C in hematopoietic cells; a source of maternal inflammation that contributes to neurodevelopmental defects; the blocking of a niche factor that promotes the growth of gliomas; and a protein that influences DNA repair pathway choice. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - October 3, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Protecting cognition from antipsychotics
Inhibiting a mechanism that mediates cognitive deficits caused by antipsychotic drugs may improve clinical outcomes for schizophrenia patients. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 26, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Tim-3 signaling in peripheral NK cells promotes maternal-fetal immune tolerance and alleviates pregnancy loss
Pregnancy loss occurs in about 15% of clinically recognized pregnancies, and defective maternal-fetal immune tolerance contributes to more than 50% of these events. We found that signaling by the type I membrane protein T cell immunoglobulin and mucin-containing protein 3 (Tim-3) in natural killer (NK) cells had an essential protective role during early pregnancy. Tim-3 on peripheral NK (pNK) cells was transiently increased in abundance during the first trimester of pregnancy, which depended on interleukin-4 (IL-4)–signal transducer and activator of transcription 6 (STAT6) and progesterone signaling. Tim-3+ pNK cells...
Source: Signal Transduction Knowledge Environment - September 26, 2017 Category: Science Authors: Li, Y., Zhang, J., Zhang, D., Hong, X., Tao, Y., Wang, S., Xu, Y., Piao, H., Yin, W., Yu, M., Zhang, Y., Fu, Q., Li, D., Chang, X., Du, M. Tags: STKE Research Articles Source Type: news

Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies
There is intense interest in developing therapeutic strategies for RAS proteins, the most frequently mutated oncoprotein family in cancer. Development of effective anti-RAS therapies will be aided by the greater appreciation of RAS isoform–specific differences in signaling events that support neoplastic cell growth. However, critical issues that require resolution to facilitate the success of these efforts remain. In particular, the use of well-validated anti-RAS antibodies is essential for accurate interpretation of experimental data. We evaluated 22 commercially available anti-RAS antibodies with a set of distinct ...
Source: Signal Transduction Knowledge Environment - September 26, 2017 Category: Science Authors: Waters, A. M., Ozkan-Dagliyan, I., Vaseva, A. V., Fer, N., Strathern, L. A., Hobbs, G. A., Tessier-Cloutier, B., Gillette, W. K., Bagni, R., Whiteley, G. R., Hartley, J. L., McCormick, F., Cox, A. D., Houghton, P. J., Huntsman, D. G., Philips, M. R., Der, Tags: STKE Research Resources Source Type: news

Dimerization of the adaptor Gads facilitates antigen receptor signaling by promoting the cooperative binding of Gads to the adaptor LAT
The accurate assembly of signalosomes centered on the adaptor protein LAT (linker of activated T cells) is required for antigen receptor signaling in T cells and mast cells. During signalosome assembly, members of the growth factor receptor–bound protein 2 (Grb2) family of cytosolic adaptor proteins bind cooperatively to LAT through interactions with its phosphorylated tyrosine (pTyr) residues. We demonstrated the Src homology 2 (SH2) domain–mediated dimerization of the Grb2 family member, Grb2-related adaptor downstream of Shc (Gads). Gads dimerization was mediated by an SH2 domain interface, which is distinct...
Source: Signal Transduction Knowledge Environment - September 26, 2017 Category: Science Authors: Sukenik, S., Frushicheva, M. P., Waknin-Lellouche, C., Hallumi, E., Ifrach, T., Shalah, R., Beach, D., Avidan, R., Oz, I., Libman, E., Aronheim, A., Lewinson, O., Yablonski, D. Tags: STKE Research Articles Source Type: news

Papers of note in Nature 549 (7672)
This week’s articles highlight the role of AMPA receptor diffusion in long-term potentiation; a mutation in an embryonic cell lineage that leads to adult neurodegeneration; the structural basis of cGAS activation; a posttranslational modification of the melanocortin-1 receptor that protects against melanoma; and factors from maternal cells that determine whether daughter cells will proliferate. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 26, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 357 (6357)
This week’s articles identify a mutation in the acetylcholine receptor that protects poison frogs from the neurotoxin that they produce; explain a key difference between neurons from Parkinson’s patients and those from mouse models of the disease; and review the intermolecular interactions that drive the formation of membraneless intracellular compartments. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 26, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (408)
This week’s articles describe new therapeutic strategies for cancer, lung inflammation, and graft-versus-host disease. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 26, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

PKD and inflammation
Protein kinase D signaling at the Golgi is required for activation of the NLRP3 inflammasome. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 19, 2017 Category: Science Authors: Foley, J. F. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 549 (7671)
This week’s articles highlight the immune response to intestinal helminth parasites and an mRNA modification that determines cell fate. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 19, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 357 (6356)
This week’s articles explain how plants establish and maintain an epigenetic memory of cold temperature and review how the engineering of channelrhodopsins as research tools has elucidated the biochemical properties of these light-activated ion channels. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 19, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Highlight: RNA-binding proteins in cancer
ADAR promotes lung adenocarcinoma migration and invasion through stabilization of FAK. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 19, 2017 Category: Science Authors: Yaffe, M. B. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (407)
This week’s articles show that blocking a prometastatic process unintentionally impairs immunotherapy and report new therapeutic targets in type 2 diabetes and asthmatic lung disease. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 19, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

The RNA-editing enzyme ADAR promotes lung adenocarcinoma migration and invasion by stabilizing FAK
Large-scale, genome-wide studies report that RNA binding proteins are altered in cancers, but it is unclear how these proteins control tumor progression. We found that the RNA-editing protein ADAR (adenosine deaminase acting on double-stranded RNA) acted as a facilitator of lung adenocarcinoma (LUAD) progression through its ability to stabilize transcripts encoding focal adhesion kinase (FAK). In samples from 802 stage I LUAD patients, increased abundance of ADAR at both the mRNA and protein level correlated with tumor recurrence. Knocking down ADAR in LUAD cells suppressed their mesenchymal properties, migration, and inva...
Source: Signal Transduction Knowledge Environment - September 19, 2017 Category: Science Authors: Amin, E. M., Liu, Y., Deng, S., Tan, K. S., Chudgar, N., Mayo, M. W., Sanchez-Vega, F., Adusumilli, P. S., Schultz, N., Jones, D. R. Tags: STKE Research Articles Source Type: news

TALK-1 channels control {beta} cell endoplasmic reticulum Ca2+ homeostasis
Ca2+ handling by the endoplasmic reticulum (ER) serves critical roles in controlling pancreatic β cell function and becomes perturbed during the pathogenesis of diabetes. ER Ca2+ homeostasis is determined by ion movements across the ER membrane, including K+ flux through K+ channels. We demonstrated that K+ flux through ER-localized TALK-1 channels facilitated Ca2+ release from the ER in mouse and human β cells. We found that β cells from mice lacking TALK-1 exhibited reduced basal cytosolic Ca2+ and increased ER Ca2+ concentrations, suggesting reduced ER Ca2+ leak. These changes in Ca2+ homeostasis were pre...
Source: Signal Transduction Knowledge Environment - September 19, 2017 Category: Science Authors: Vierra, N. C., Dadi, P. K., Milian, S. C., Dickerson, M. T., Jordan, K. L., Gilon, P., Jacobson, D. A. Tags: STKE Research Articles Source Type: news

Microtubule structures underlying the sarcoplasmic reticulum support peripheral coupling sites to regulate smooth muscle contractility
Junctional membrane complexes facilitate excitation-contraction coupling in skeletal and cardiac muscle cells by forming subcellular invaginations that maintain close (≤20 nm) proximity of ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR) with voltage-dependent Ca2+ channels in the plasma membrane. In fully differentiated smooth muscle cells, junctional membrane complexes occur as distributed sites of peripheral coupling. We investigated the role of the cytoskeleton in maintaining peripheral coupling and associated Ca2+ signaling networks within native smooth muscle cells of mouse and rat cerebral arteries. ...
Source: Signal Transduction Knowledge Environment - September 19, 2017 Category: Science Authors: Pritchard, H. A. T., Gonzales, A. L., Pires, P. W., Drumm, B. T., Ko, E. A., Sanders, K. M., Hennig, G. W., Earley, S. Tags: STKE Research Articles Source Type: news

Paper of note in Science Translational Medicine 9 (406)
This week’s article describes how targeted antimicrobials may reduce the virulence of Clostridium difficile infection. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 12, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Chemotherapy, pain, and gut microbiota
Chemotherapy triggers gut microbiota to stimulate pain-associated peripheral inflammation. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 12, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Leaky nuclei lead to senescence
A pathway that senses microbial DNA also promotes senescence in cells with cytosolic chromatin fragments. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 12, 2017 Category: Science Authors: Wong, W. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 549 (7670)
This week’s articles identify microbial metabolites that stimulate GPCRs; a transmembrane protein that maintains PD-L1 at the plasma membrane; immune enhancer elements that respond to specific extracellular signals; a signaling pathway that defines the right side of the vertebrate embryo; functions for ionotropic glutamate receptors in plants; and structural features of AMPA receptors during activation and desensitization. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 12, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 357 (6355)
This week’s articles describe an alternative mechanism of secretion that is deployed by intestinal cells in the presence of pathogens; how the immune system protects the lungs from inhaled fungal spores; and metabolic reprogramming of tissue-resident antigen-presenting cells in the lung. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 12, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Regulation of autophagy, NF-{kappa}B signaling, and cell viability by miR-124 in KRAS mutant mesenchymal-like NSCLC cells
KRAS mutant non–small cell lung cancer (NSCLC) may be classified into epithelial or mesenchymal subtypes. Despite having the same "driver" mutation, mesenchymal NSCLCs are less responsive than are epithelial NSCLCs to inhibition of the RAS pathway. Identifying alternative networks that promote survival specifically in mesenchymal NSCLC may lead to more effective treatments for this subtype. Through their numerous targets in cellular signaling pathways, noncoding microRNAs (miRNAs) often function as tumor suppressors or oncogenes. In particular, some miRNAs regulate the epithelial-mesenchymal transition (EMT...
Source: Signal Transduction Knowledge Environment - September 12, 2017 Category: Science Authors: Mehta, A. K., Hua, K., Whipple, W., Nguyen, M.-T., Liu, C.-T., Haybaeck, J., Weidhaas, J., Settleman, J., Singh, A. Tags: STKE Research Articles Source Type: news

A natural ligand for the orphan receptor GPR15 modulates lymphocyte recruitment to epithelia
We describe the purification from porcine colonic tissue extracts of an agonistic ligand for GPR15 and its functional characterization. In humans, this ligand, which we named GPR15L, is encoded by the gene C10ORF99 and has some features similar to the CC family of chemokines. GPR15L was found in some human and mouse epithelia exposed to the environment, such as the colon and skin. In humans, GPR15L was also abundant in the cervix. In skin, GPR15L was readily detected after immunologic challenge and in human disease, for example, in psoriatic lesions. Allotransplantation of skin from Gpr15l-deficient mice onto wild-type mic...
Source: Signal Transduction Knowledge Environment - September 12, 2017 Category: Science Authors: Suply, T., Hannedouche, S., Carte, N., Li, J., Grosshans, B., Schaefer, M., Raad, L., Beck, V., Vidal, S., Hiou-Feige, A., Beluch, N., Barbieri, S., Wirsching, J., Lageyre, N., Hillger, F., Debon, C., Dawson, J., Smith, P., Lannoy, V., Detheux, M., Bitsch Tags: STKE Research Articles Source Type: news

Cancer-associated arginine-to-histidine mutations confer a gain in pH sensing to mutant proteins
The intracellular pH (pHi) of most cancers is constitutively higher than that of normal cells and enhances proliferation and cell survival. We found that increased pHi enabled the tumorigenic behaviors caused by somatic arginine-to-histidine mutations, which are frequent in cancer and confer pH sensing not seen with wild-type proteins. Experimentally raising the pHi increased the activity of R776H mutant epidermal growth factor receptor (EGFR-R776H), thereby increasing proliferation and causing transformation in fibroblasts. An Arg-to-Gly mutation did not confer these effects. Molecular dynamics simulations of EGFR suggest...
Source: Signal Transduction Knowledge Environment - September 5, 2017 Category: Science Authors: White, K. A., Ruiz, D. G., Szpiech, Z. A., Strauli, N. B., Hernandez, R. D., Jacobson, M. P., Barber, D. L. Tags: STKE Research Articles Source Type: news

New connections: Pleiotrophin and glioma
The cytokine pleiotrophin promotes the invasion and vascularization of glioma. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 5, 2017 Category: Science Authors: Wong, W. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 357 (6354)
This week’s articles describe how glia contribute to visual system development; a potential therapy for Parkinson’s disease; and how gut microbes regulate body composition. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 5, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (405)
This week’s articles describe how the immune system in some children is better able to cope with dengue virus infection; how targeting a specific population of monocytes may relieve persistent inflammation associated with HIV infection; and how targeting the vascular niche may suppress fibrosis around lung and liver engraftments. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 5, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 548 (7669)
This week’s articles describe molecular changes in tumors that affect the efficacy of immunotherapies; signaling mechanisms that mediate the CRISPR system in prokaryotes and regulatory T cell function in mammals; and a mechanism that maintains healthy tissue turnover in the gut. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 5, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Bacterial D-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells
In the upper respiratory epithelium, bitter and sweet taste receptors present in solitary chemosensory cells influence antimicrobial innate immune defense responses. Whereas activation of bitter taste receptors (T2Rs) stimulates surrounding epithelial cells to release antimicrobial peptides, activation of the sweet taste receptor (T1R) in the same cells inhibits this response. This mechanism is thought to control the magnitude of antimicrobial peptide release based on the sugar content of airway surface liquid. We hypothesized that d-amino acids, which are produced by various bacteria and activate T1R in taste receptor cel...
Source: Signal Transduction Knowledge Environment - September 5, 2017 Category: Science Authors: Lee, R. J., Hariri, B. M., McMahon, D. B., Chen, B., Doghramji, L., Adappa, N. D., Palmer, J. N., Kennedy, D. W., Jiang, P., Margolskee, R. F., Cohen, N. A. Tags: STKE Research Articles Source Type: news

Ca2+ and mitochondrial ROS: Both hero and villain in membrane repair
Membrane repair is a symphony of signaling, conducted principally by the steep influx of Ca2+ through an injured membrane. In this issue of Science Signaling, Horn et al. reveal unique interplay between Ca2+ influx and mitochondrially generated reactive oxygen species (mtROS) to enhance actin-mediated wound closure for survival of injured mammalian muscle and nonmuscle cells. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - September 5, 2017 Category: Science Authors: Cooper, S. T. Tags: STKE Focus Source Type: news

Mitochondrial redox signaling enables repair of injured skeletal muscle cells
Strain and physical trauma to mechanically active cells, such as skeletal muscle myofibers, injures their plasma membranes, and mitochondrial function is required for their repair. We found that mitochondrial function was also needed for plasma membrane repair in myoblasts as well as nonmuscle cells, which depended on mitochondrial uptake of calcium through the mitochondrial calcium uniporter (MCU). Calcium uptake transiently increased the mitochondrial production of reactive oxygen species (ROS), which locally activated the guanosine triphosphatase (GTPase) RhoA, triggering F-actin accumulation at the site of injury and f...
Source: Signal Transduction Knowledge Environment - September 5, 2017 Category: Science Authors: Horn, A., Van der Meulen, J. H., Defour, A., Hogarth, M., Sreetama, S. C., Reed, A., Scheffer, L., Chandel, N. S., Jaiswal, J. K. Tags: STKE Research Articles Source Type: news

Blockade of surface-bound TGF-{beta} on regulatory T cells abrogates suppression of effector T cell function in the tumor microenvironment
Regulatory T cells (Tregs) suppress antitumor immunity by inhibiting the killing of tumor cells by antigen-specific CD8+ T cells. To better understand the mechanisms involved, we used ex vivo three-dimensional collagen-fibrin gel cultures of dissociated B16 melanoma tumors. This system recapitulated the in vivo suppression of antimelanoma immunity, rendering the dissociated tumor cells resistant to killing by cocultured activated, antigen-specific T cells. Immunosuppression was not observed when tumors excised from Treg-depleted mice were cultured in this system. Experiments with neutralizing antibodies showed that blockin...
Source: Signal Transduction Knowledge Environment - August 29, 2017 Category: Science Authors: Budhu, S., Schaer, D. A., Li, Y., Toledo-Crow, R., Panageas, K., Yang, X., Zhong, H., Houghton, A. N., Silverstein, S. C., Merghoub, T., Wolchok, J. D. Tags: STKE Research Articles Source Type: news

Papers of note in Nature 548 (7668)
This week’s articles describe how the stroma promotes tissue regeneration in the stomach; show how mitosis, the DNA sensor cGAS, and CDK inhibitors contribute to antitumor immunity; and describe the mechanism of action of an allosteric beta blocker. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - August 29, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 357 (6353)
This week’s articles describe the signals mediating gut microbe activation of T cells, skin patterning in development, and photosynthesis. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - August 29, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (404)
This week’s articles describe potential therapeutic strategies to reduce hydrocephaly in infants, to kill liver cancer cells, and to improve MeCP2-associated neurological disorders. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - August 29, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

An epigenetic tactic to treat RMS
BET inhibitors may be an effective treatment for some rhabdomyosarcomas. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - August 29, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Activation of master virulence regulator PhoP in acidic pH requires the Salmonella-specific protein UgtL
Acidic conditions, such as those inside phagosomes, stimulate the intracellular pathogen Salmonella enterica to activate virulence genes. The sensor PhoQ responds to a mildly acidic pH by phosphorylating, and thereby activating, the virulence regulator PhoP. This PhoP/PhoQ two-component system is conserved in a subset of Gram-negative bacteria. PhoQ is thought to be sufficient to activate PhoP in mildly acidic pH. However, we found that the Salmonella-specific protein UgtL, which was horizontally acquired by Salmonella before the divergence of S. enterica and Salmonella bongori, was also necessary for PhoQ to activate PhoP...
Source: Signal Transduction Knowledge Environment - August 29, 2017 Category: Science Authors: Choi, J., Groisman, E. A. Tags: STKE Research Articles Source Type: news