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A cryo-EM-based model of phosphorylation- and FKBP12.6-mediated allosterism of the cardiac ryanodine receptor
Type 2 ryanodine receptors (RyR2s) are calcium channels that play a vital role in triggering cardiac muscle contraction by releasing calcium from the sarcoplasmic reticulum into the cytoplasm. Several cardiomyopathies are associated with the abnormal functioning of RyR2. We determined the three-dimensional structure of rabbit RyR2 in complex with the regulatory protein FKBP12.6 in the closed state at 11.8 Å resolution using cryo-electron microscopy and built an atomic model of RyR2. The heterogeneity in the data set revealed two RyR2 conformations that we proposed to be related to the extent of phosphorylation of the...
Source: Signal Transduction Knowledge Environment - May 23, 2017 Category: Science Authors: Dhindwal, S., Lobo, J., Cabra, V., Santiago, D. J., Nayak, A. R., Dryden, K., Samso, M. Tags: STKE Research Articles Source Type: news

Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2
Chemokines and their receptors collectively orchestrate the trafficking of leukocytes in normal immune function and inflammatory diseases. Different chemokines can induce distinct responses at the same receptor. In comparison to monocyte chemoattractant protein-1 (MCP-1; also known as CCL2), the chemokines MCP-2 (CCL8) and MCP-3 (CCL7) are partial agonists of their shared receptor CCR2, a key regulator of the trafficking of monocytes and macrophages that contribute to the pathology of atherosclerosis, obesity, and type 2 diabetes. Through experiments with chimeras of MCP-1 and MCP-3, we identified the chemokine amino-termi...
Source: Signal Transduction Knowledge Environment - May 23, 2017 Category: Science Authors: Huma, Z. E., Sanchez, J., Lim, H. D., Bridgford, J. L., Huang, C., Parker, B. J., Pazhamalil, J. G., Porebski, B. T., Pfleger, K. D. G., Lane, J. R., Canals, M., Stone, M. J. Tags: STKE Research Articles Source Type: news

Receptor cooperation in B cells
TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 23, 2017 Category: Science Authors: Foley, J. F. Tags: STKE Editors ' Choice Source Type: news

New connections: How to become more flexible and open up
Cryo-EM–generated structures provide insight into how RyR2 is gated and how phosphorylation may affect the activation process. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 23, 2017 Category: Science Authors: Wong, W. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 545 (7654)
This week’s articles highlight plant growth responses to nutrients; axonal pathfinding; an unexpected source of tumor niche cells; photosensation in the fly brain; the selectivity of GPCRs for specific G proteins; balancing mTORC signaling; and a connection between gut microbes and brain vasculature malformations. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 23, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Androgen receptor inhibitor-induced "BRCAness" and PARP inhibition are synthetically lethal for castration-resistant prostate cancer
Cancers with loss-of-function mutations in BRCA1 or BRCA2 are deficient in the DNA damage repair pathway called homologous recombination (HR), rendering these cancers exquisitely vulnerable to poly(ADP-ribose) polymerase (PARP) inhibitors. This functional state and therapeutic sensitivity is referred to as "BRCAness" and is most commonly associated with some breast cancer types. Pharmaceutical induction of BRCAness could expand the use of PARP inhibitors to other tumor types. For example, BRCA mutations are present in only ~20% of prostate cancer patients. We found that castration-resistant prostate cancer (CRPC)...
Source: Signal Transduction Knowledge Environment - May 23, 2017 Category: Science Authors: Li, L., Karanika, S., Yang, G., Wang, J., Park, S., Broom, B. M., Manyam, G. C., Wu, W., Luo, Y., Basourakos, S., Song, J. H., Gallick, G. E., Karantanos, T., Korentzelos, D., Azad, A. K., Kim, J., Corn, P. G., Aparicio, A. M., Logothetis, C. J., Troncoso Tags: STKE Research Articles Source Type: news

Papers of note in Science Translational Medicine 9 (390)
This week’s articles describe new treatments for heart failure and its associated symptoms and a sequential gene delivery system to regenerate fractured bone. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 23, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 356 (6339)
This week’s articles identify a repulsive guidance system that controls the recruitment of T cells to germinal centers; a mechanism for controlling the transfer of nutrients from the placenta to early mouse embryos; and the subcellular location of calcium dynamics in astrocytes. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 23, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

New connections: The duality of ROS in angiogenesis
Depending on the tissue and context, ROS can either stimulate or suppress blood vessel formation. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Authors: Wong, W. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 545 (7653)
This week’s articles highlight colon cancer stem cells; cooperative signaling that maintains intestinal stem cell self-renewal; a newly developed Wnt agonist; and metabolic changes in endothelial cells that promote angiogenesis. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 356 (6338)
This week’s articles demonstrate how T cells search for ligands; a role for the endoplasmic reticulum in the nonclathrin-mediated endocytosis of a growth factor receptor; and growth coupling between distant bacterial colonies that enables the cells to share limited resources. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (389)
This week’s articles highlight how tumor-associated macrophages limit the efficacy of PD-1–targeted checkpoint therapy and show that an anti-inflammatory drug may be used to treat lymphedema. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Quorum sensing to repress virulence
A quorum-sensing system of an insect endosymbiont enables the bacterium to establish persistent infection by inhibiting the expression of virulence genes. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Erratum for the Research Article: "Reactive oxygen species induce virus-independent MAVS oligomerization in systemic lupus erythematosus" by I. A. Buskiewicz, T. Montgomery, E. C. Yasewicz, S. A. Huber, M. P. Murphy, R. C. Hartley, R. Kelly, M. K. Crow, A. Perl, R. C. Budd, A. Koenig
(Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Tags: STKE Errata Source Type: news

Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes
We examined the role of ROS in preeclampsia by genetically modifying the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular antioxidant responses; however, Nrf2 deficiency in preeclamptic mice improved maternal and fetal survival, ameliorated intra-uterine growth retardation, and augmented oxidative DNA damage. Furthermore, the placentas of Nrf2-deficient mice had increased endothelial cell proliferation with dense vascular networks. In contrast, the placentas of preeclamptic mice with overactive Nrf2 showed repressed...
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Authors: Nezu, M., Souma, T., Yu, L., Sekine, H., Takahashi, N., Wei, A. Z.-S., Ito, S., Fukamizu, A., Zsengeller, Z. K., Nakamura, T., Hozawa, A., Karumanchi, S. A., Suzuki, N., Yamamoto, M. Tags: STKE Research Articles Source Type: news

Science Signaling Podcast for 16 May 2017: Vibrio rewires host cells
Abstract This Podcast features a conversation with Kim Orth and Nicole De Nisco, authors of a Research Resource that appears in the 16 May 2017 issue of Science Signaling, about how the marine bacterium Vibrio parahaemolyticus rewires host cell signaling networks. V. parahaemolyticus thrives in warm brackish waters and infects both shellfish and finfish. This bacterium causes gastroenteritis when humans consume contaminated seafood that is raw or undercooked. V. parahaemolyticus delivers virulence factors into host cells through two different type 3 secretion systems (T3SSes). Whereas T3SS2 mediates gastroenteritis, T3SS1 ...
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Authors: De Nisco, N. J., Orth, K., VanHook, A. M. Tags: STKE Podcasts Source Type: news

The cytotoxic type 3 secretion system 1 of Vibrio rewires host gene expression to subvert cell death and activate cell survival pathways
Bacterial effectors potently manipulate host signaling pathways. The marine bacterium Vibrio parahaemolyticus (V. para) delivers effectors into host cells through two type 3 secretion systems (T3SSs). T3SS1 is vital for V. para survival in the environment, whereas T3SS2 causes acute gastroenteritis in human hosts. Although the natural host is undefined, T3SS1 effectors attack highly conserved cellular processes and pathways to orchestrate nonapoptotic cell death. To understand how the concerted action of T3SS1 effectors globally affects host cell signaling, we compared gene expression changes over time in primary fibroblas...
Source: Signal Transduction Knowledge Environment - May 16, 2017 Category: Science Authors: De Nisco, N. J., Kanchwala, M., Li, P., Fernandez, J., Xing, C., Orth, K. Tags: STKE Research Resources Source Type: news

LDL cholesterol impairs therapy
A diet high in LDL cholesterol may hinder the therapeutic efficacy of tyrosine kinase inhibitors in cancer patients. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Epithelial cells reject abnormal neighbors
Normal epithelial cells induce metabolic changes in neighboring transformed cells to force them out of the epithelium. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Paper of note in Science Translational Medicine 9 (388)
This week’s article uncovers why mutations in the vesicular trafficking protein annexin 11 are implicated in the neurodegenerative disease ALS. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 545 (7652)
This week’s articles highlight a role for a polyglutamine tract in regulating autophagy; how cytokinesis affects the mechanosensitivity of cell junctions; the effect of interferon- on tumor vasculature; advances in human brain organoid technology; and biochemical features of a receptor that may aid in developing drugs that specifically target the receptor. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 356 (6337)
This week’s articles address the role of macrophage metabolic reprogramming in resolving inflammation and an epidermal pattern formation system that is self-organizing and can adjust to fit the size of the tissue. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Membrane depolarization activates BK channels through ROCK-mediated {beta}1 subunit surface trafficking to limit vasoconstriction
Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca2+)–activated potassium (BK) channels, which limits Ca2+ channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels. Membrane depolarization stimulated voltage-dependent Ca2+ channels,...
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: Leo, M. D., Zhai, X., Muralidharan, P., Kuruvilla, K. P., Bulley, S., Boop, F. A., Jaggar, J. H. Tags: STKE Research Articles Source Type: news

Science Signaling Podcast for 9 May 2017: Trafficking of BK channel subunits in arterial myocytes
Abstract This Podcast features a conversation with Jonathan Jaggar, senior author of a Research Article that appears in the 9 May 2017 issue of Science Signaling, about trafficking of big potassium (BK) channel subunits in arterial myocytes. Depolarization of the arterial myocyte membrane causes a rise in intracellular calcium that stimulates the cell to contract, which leads to vasoconstriction. Membrane depolarization also activates BK channels, which allow potassium to flow out of the cell, thus repolarizing the membrane and promoting vasodilation. Leo et al. found that a critical aspect of this negative feedback mechan...
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: Jaggar, J. H., VanHook, A. M. Tags: STKE Podcasts Source Type: news

Tetraspanin microdomains control localized protein kinase C signaling in B cells
Activation of B cells by the binding of antigens to the B cell receptor (BCR) requires the protein kinase C (PKC) family member PKCβ. Because PKCs must translocate to the plasma membrane to become activated, we investigated the mechanisms regulating their spatial distribution in mouse and human B cells. Through live-cell imaging, we showed that BCR-stimulated production of the second messenger diacylglycerol (DAG) resulted in the translocation of PKCβ from the cytosol to plasma membrane regions containing the tetraspanin protein CD53. CD53 was specifically enriched at sites of BCR signaling, suggesting that BCR-d...
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: Zuidscherwoude, M., Dunlock, V.-M. E., van den Bogaart, G., van Deventer, S. J., van der Schaaf, A., van Oostrum, J., Goedhart, J., In 't Hout, J., Hämmerling, G. J., Tanaka, S., Nadler, A., Schultz, C., Wright, M. D., Adjobo-Hermans, M. J. W., va Tags: STKE Research Articles Source Type: news

The amyloid-{beta} oligomer A{beta}*56 induces specific alterations in neuronal signaling that lead to tau phosphorylation and aggregation
Oligomeric forms of amyloid-forming proteins are believed to be the principal initiating bioactive species in many neurodegenerative disorders, including Alzheimer’s disease (AD). Amyloid-β (Aβ) oligomers are implicated in AD-associated phosphorylation and aggregation of the microtubule-associated protein tau. To investigate the specific molecular pathways activated by different assemblies, we isolated various forms of Aβ from Tg2576 mice, which are a model for AD. We found that Aβ*56, a 56-kDa oligomer that is detected before patients develop overt signs of AD, induced specific changes in neurona...
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: Amar, F., Sherman, M. A., Rush, T., Larson, M., Boyle, G., Chang, L., Götz, J., Buisson, A., Lesne, S. E. Tags: STKE Research Articles Source Type: news

Hyperactive locomotion in a Drosophila model is a functional readout for the synaptic abnormalities underlying fragile X syndrome
We report that larval locomotion is augmented in a Drosophila FXS model. Genetic or pharmacological intervention on the BMPR2-LIMK pathway ameliorated the synaptic abnormality and locomotion phenotypes of FXS larvae, as well as hyperactivity in an FXS mouse model. Our study demonstrates that (i) the BMPR2-LIMK pathway is a promising therapeutic target for FXS and (ii) the locomotion phenotype of FXS larvae is a quantitative functional readout for the neuromorphological phenotype associated with FXS and is amenable to the screening novel FXS therapeutics. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: Kashima, R., Redmond, P. L., Ghatpande, P., Roy, S., Kornberg, T. B., Hanke, T., Knapp, S., Lagna, G., Hata, A. Tags: STKE Research Resources Source Type: news

Sorting out memory and learning
Mutations in AMPA receptor recycling machinery underlie cognitive impairment in an intellectual disorder and in neurodegenerative diseases. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Immunology 2 (10)
This month’s articles show that cholesterol-based ligands position splenic dendritic cells near T cells; how synovial fibroblasts and neutrophils promote inflammation in arthritis; that type I interferon activates liver T cells in obese mice; and how the alternative complement pathway plays a role in antibacterial immunity. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: Foley, J. F. Tags: STKE Editors ' Choice Source Type: news

New connections: Treating fragile X syndrome
An in vivo drug screen can identify inhibitors of the signaling pathway that is activated in fragile X syndrome. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Shutting down innate immune responses during fertilization
The inflammasome component NLRP14 inhibits the nucleic acid sensing pathway during fertilization. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: Foley, J. F. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (387)
This week’s articles reveal a new treatment for malaria and an adjunct therapy that may reduce the hematologic toxicity of chemotherapy. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Paper of note in Nature 544 (7651)
This week’s article identifies a receptor that is important for phagocytosis of some tumor cells by macrophages. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 356 (6336)
This week’s articles highlight the importance of protocadherins in the developing nervous system and the mechanism by which plants limit the number of germ cells derived from somatic cells. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

BMP8A sustains spermatogenesis by activating both SMAD1/5/8 and SMAD2/3 in spermatogonia
Mutation in either of the genes encoding bone morphogenetic protein (BMP) 8A or 8B (Bmp8a or Bmp8b) causes postnatal depletion of spermatogonia in mice. We found that Bmp8a, but not Bmp8b, was expressed predominantly in the neonatal mouse spermatogonia. Although most BMPs induce activation of SMADs 1, 5, and 8 (SMAD1/5/8), but not SMADs 2 and 3 (SMAD2/3), we found that BMP8A induced signaling through both sets of transcription factors. In undifferentiated mouse spermatogonia, BMP8A activated SMAD1/5/8 through receptor complexes formed by ALK3 and either ACVR2A or BMPR2 and activated SMAD2/3 through receptor complexes forme...
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: Wu, F.-J., Lin, T.-Y., Sung, L.-Y., Chang, W.-F., Wu, P.-C., Luo, C.-W. Tags: STKE Research Articles Source Type: news

Genome-wide identification and characterization of Notch transcription complex-binding sequence-paired sites in leukemia cells
Notch transcription complexes (NTCs) drive target gene expression by binding to two distinct types of genomic response elements, NTC monomer–binding sites and sequence-paired sites (SPSs) that bind NTC dimers. SPSs are conserved and have been linked to the Notch responsiveness of a few genes. To assess the overall contribution of SPSs to Notch-dependent gene regulation, we determined the DNA sequence requirements for NTC dimerization using a fluorescence resonance energy transfer (FRET) assay and applied insights from these in vitro studies to Notch-"addicted" T cell acute lymphoblastic leukemia (T-ALL) cel...
Source: Signal Transduction Knowledge Environment - May 2, 2017 Category: Science Authors: Severson, E., Arnett, K. L., Wang, H., Zang, C., Taing, L., Liu, H., Pear, W. S., Shirley Liu, X., Blacklow, S. C., Aster, J. C. Tags: STKE Research Articles Source Type: news

p53 dynamics in response to DNA damage vary across cell lines and are shaped by efficiency of DNA repair and activity of the kinase ATM
Cellular systems show a wide range of signaling dynamics. Many of these dynamics are highly stereotyped, such as oscillations at a fixed frequency. However, most studies looking at the role of signaling dynamics focus on one or a few cell lines, leaving the diversity of dynamics across tissues or cell lines a largely unexplored question. We focused on the dynamics of the tumor suppressor protein p53, which regulates cell cycle arrest and apoptosis in response to DNA damage. We established live-cell reporters for 12 cancer cell lines expressing wild-type p53 and quantified p53 dynamics in response to double-strand break&nda...
Source: Signal Transduction Knowledge Environment - April 25, 2017 Category: Science Authors: Stewart-Ornstein, J., Lahav, G. Tags: STKE Research Articles Source Type: news

Discovering relationships between nuclear receptor signaling pathways, genes, and tissues in Transcriptomine
We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biology in these pathways using this tool. Transcriptomine currently contains about 45 million data points encompassing more than 2000 experiments in a reference library of nearly 550 data sets retrieved from public archives and systematically curated. To make the underlying data points more accessible to bench biologists, we classified experimental small molecules and gene manipulations into signaling pathways and experimental tissues and cell lines into physiological systems and organs. Incorp...
Source: Signal Transduction Knowledge Environment - April 25, 2017 Category: Science Authors: Becnel, L. B., Ochsner, S. A., Darlington, Y. F., McOwiti, A., Kankanamge, W. H., Dehart, M., Naumov, A., McKenna, N. J. Tags: STKE Research Resources Source Type: news

Blocking a signal to host cell histones
A plant pathogen suppresses the host immune response by preventing histone acetylation. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 25, 2017 Category: Science Authors: Mushegian, A. A. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science 356 (6335)
This week’s articles highlight a peptide that controls myoblast fusion; a metabolic adaptation that enables naked mole-rats to resist the detrimental effects of anoxia; a transcription factor that coordinates signaling in the mammary epithelial stem cell niche; and transgenerational epigenetic inheritance of the response to an environmental stimulus. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 25, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (386)
This week’s articles describe a new hydrogel that promotes chronic wound healing and a way to limit intestinal tissue damage from radiation, chemo, or hematopoietic cell transplant therapies. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 25, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Active life, active antitumor defense
An active lifestyle in mice stimulates adrenergic signaling in the nervous system that enhances the function of antitumor natural killer cells. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 25, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Nature 544 (7650)
This week’s articles show that vesicle fusion proteins are involved in long-term potentiation and highlight the structural properties that contribute to functional differences between angiotensin II receptors. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 25, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated genes to protect against viral infections
Interferon (IFN)–stimulated genes (ISGs) are antiviral effectors that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we found that IFN-independent ISG expression was detectable in immortalized cell lines, primary intestinal and liver organoids, and liver tissues. The constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U-ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and STAT2. Under homeostatic conditions, STAT1, STAT2, and IRF9 were found in the nucle...
Source: Signal Transduction Knowledge Environment - April 25, 2017 Category: Science Authors: Wang, W., Yin, Y., Xu, L., Su, J., Huang, F., Wang, Y., Boor, P. P. C., Chen, K., Wang, W., Cao, W., Zhou, X., Liu, P., van der Laan, L. J. W., Kwekkeboom, J., Peppelenbosch, M. P., Pan, Q. Tags: STKE Research Articles Source Type: news

The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens. RCM-1 blocked the nuclear localization and increased the proteasomal degradation of Forkhead box M1 (FOXM1), a tran...
Source: Signal Transduction Knowledge Environment - April 18, 2017 Category: Science Authors: Sun, L., Ren, X., Wang, I.-C., Pradhan, A., Zhang, Y., Flood, H. M., Han, B., Whitsett, J. A., Kalin, T. V., Kalinichenko, V. V. Tags: STKE Research Articles Source Type: news

Stress signals in plants
Selective autophagy mediates the cross-talk between plant growth and stress signaling pathways. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 18, 2017 Category: Science Authors: Mushegian, A. A. Tags: STKE Editors ' Choice Source Type: news

Microbes stimulate hair follicles
Commensal microbes induce hair follicles to release a chemokine that recruits regulatory T cells into neonatal skin. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 18, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

Papers of note in Science Translational Medicine 9 (385)
This week’s articles show that combining antiangiogenic therapy and immune checkpoint inhibition improves antitumor immunity. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 18, 2017 Category: Science Authors: Ferrarelli, L. K. Tags: STKE Editors ' Choice Source Type: news

Paper of note in Science 356 (6334)
This week’s article highlights the contribution of T cell reactivity to nonviral antigens to the success of adoptive T cell transfer in treating a virus-driven cancer. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - April 18, 2017 Category: Science Authors: VanHook, A. M. Tags: STKE Editors ' Choice Source Type: news

The kinase TPL2 activates ERK and p38 signaling to promote neutrophilic inflammation
We describe a conserved and critical role for TPL2 in mediating the effector functions of neutrophils through the activation of the p38 MAPK signaling pathway. Gene expression profiling and functional studies of neutrophils and monocytes revealed a MEK1/2-independent branch point downstream of TPL2 in neutrophils. Biochemical analyses identified the MAPK kinases MEK3 and MEK6 and the MAPKs p38α and p38 as downstream effectors of TPL2 in these cells. Genetic ablation of the catalytic activity of TPL2 or therapeutic intervention with a TPL2-specific inhibitor reduced the production of inflammatory mediators by neutroph...
Source: Signal Transduction Knowledge Environment - April 18, 2017 Category: Science Authors: Senger, K., Pham, V. C., Varfolomeev, E., Hackney, J. A., Corzo, C. A., Collier, J., Lau, V. W. C., Huang, Z., Hamidzhadeh, K., Caplazi, P., Peng, I., Setiadi, A. F., Francis, R., Paler-Martinez, A., Kwon, Y. C., Ramirez-Carrozzi, V., Sun, Y., Grigg, P. W Tags: STKE Research Articles Source Type: news