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Cellular Signalling

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https://www.readbyqxmd.com/read/27915047/physical-and-functional-interaction-of-snapin-with-cav1-3-calcium-channel-impacts-channel-protein-trafficking-in-atrial-myocytes
#1
Xiao-Li Sun, Ju-Fang Yuan, Tao Jin, Xiao-Qing Cheng, Qiang Wang, Jia Guo, Wei Zhang, Yin Zhang, Ling Lu, Zhao Zhang
The L-type Ca(2+) channel (LTCC) Cav1.3 plays a critical role in generating electrical activity in atrial myocytes and cardiac pacemaker cells. However, the molecular and functional basis of Cav1.3 modulation in atrial myocytes has not yet been fully understood. By using the yeast two-hybrid system (Y2H), a Cav1.3-associated protein was screened, which was identified as Snapin. Physical interaction and co-localization between Snapin and Cav1.3 were then confirmed in both the heterologous expression system and mouse atrial myocytes...
December 1, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27890558/ask1-regulates-the-survival-of-neuroblastoma-cells-by-interacting-with-tlx-and-stabilizing-hif-1%C3%AE
#2
Praveen K Sobhan, Qiwei Zhai, Lydia C Green, Loen M Hansford, Keiko Funa
Elevated expression of TLX (also called as NR2E1) in neuroblastoma (NB) correlates with unfavorable prognosis, and TLX is required for self-renewal of NB cells. Knockdown of TLX has been shown to reduce the NB sphere-forming ability. ASK1 (MAP3K5) and TLX expression are both enhanced in SP (side population) NB and patient-derived primary NB sphere cell lines, but the majority of non-SP NB lines express lower ASK1 expression. We found that ASK1 phosphorylated and stabilized TLX, which led induction of HIF-1α, and its downstream VEGF-A in an Akt dependent manner...
November 24, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27887991/vcp-p97-regulates-%C3%AE-2ar-quality-control-during-receptor-biosynthesis
#3
Richard Wargachuk, Irina Glazkova, Nicolas Audet, Darlaine Pétrin, Phan Trieu, Terence E Hébert
GPCRs form signalling complexes with other receptors as part of dimers, G proteins and effector partners. A proteomic screen to identify proteins that associate with the β2-adrenergic receptor (β2AR) identified many of components of the Endoplasmic-Reticulum-Associated Degradation (ERAD) quality control system [1], including the valosin-containing protein (VCP/p97). Here, we validated the interaction of VCP with co-expressed FLAG-β2AR, demonstrating, using an inducible expression system, that the interaction of FLAG-β2AR and VCP is not an artifact of overexpression of the β2AR per se...
November 22, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27884734/nitric-oxide-coupled-signaling-in-odor-elicited-molecular-events-in-the-olfactory-center-of-the-terrestrial-snail-helix-pomatia
#4
Zoltán Serfőző, Kálmán Nacsa, Zoltán Veréb, Izabella Battonyai, Csaba Hegedűs, Csilla Balogh, Károly Elekes
Olfaction, a chemosensory modality, plays a pivotal role in the orientation and behavior of invertebrates. The central olfactory processing unit in terrestrial stylomatophoran snails is the procerebrum, which contains NO synthesizing interneurons, whose oscillatory currents are believed to be the base of odor evoked memory formation. Nevertheless, in this model the up- and downstream events of molecular cascades that trigger and follow NO release, respectively, have not been studied. Immunocytochemistry and flow cytometry studies performed on procerebral neural perikarya isolated from the snail Helix pomatia revealed cell populations with discrete DAF-2 fluorescence, indicating the release of different amounts of NO...
November 21, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27871936/commd9-promotes-tfdp1-e2f1-transcriptional-activity-via-interaction-with-tfdp1-in-non-small-cell-lung-cancer
#5
Weihua Zhan, Wenjuan Wang, Tianyu Han, Caifeng Xie, Tingting Zhang, Mingxi Gan, Jian-Bin Wang
COMMD protein family is an evolutionarily conserved gene family implicated in a number of critical processes including inflammation, copper homeostasis, sodium balance, endosomal sorting and cancer. In an effort to profile the expression pattern of COMMD family in several non-small cell lung cancer (NSCLC) cell lines, we found that compared with that in human bronchial epithelial (HBE) cells, the mRNA expression levels of five COMMD genes including COMMD3, COMMD4, COMMD5, COMMD6 and COMMD8 were significantly down-regulated, whereas COMMD9 was up-regulated in NSCLC cell lines...
November 19, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27871937/elevated-levels-of-alpha-synuclein-blunt-cellular-signal-transduction-downstream-of-gq-protein-coupled-receptors
#6
Mattia Volta, Alexandros A Lavdas, Julia Obergasteiger, Christa Überbacher, Anne Picard, Peter P Pramstaller, Andrew A Hicks, Corrado Corti
Alpha-synuclein is central to Parkinson's disease pathogenesis and pathology, however its precise functions are still unclear. It has been shown to bind both PLCβ1 and MAPKs, but how this property influences the downstream signaling of Gq protein-coupled receptors has not been elucidated. Here we show that recombinant expression of alpha-synuclein in human neuroblastoma cells enhances cellular levels of PLCβ1 but blunts its signaling pathway, preventing the agonist-dependent rise of cytoplasmic Ca(2+). In addition, overexpressing alpha-synuclein abolishes the activation of ERK1/2 upon agonist stimulation, indicating an upstream action in the signal transduction pathway...
November 18, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27871935/a-sonic-hedgehog-coreceptor-boc-regulates-neuronal-differentiation-and-neurite-outgrowth-via-interaction-with-abl-and-jnk-activation
#7
Tuan Anh Vuong, Young-Eun Leem, Bok-Geon Kim, Hana Cho, Sang-Jin Lee, Gyu-Un Bae, Jong-Sun Kang
Neurite outgrowth is a critical step for neurogenesis and remodeling synaptic circuitry during neuronal development and regeneration. An immunoglobulin superfamily member, BOC functions as Sonic hedgehog (Shh) coreceptor in canonical and noncanonical Shh signaling in neuronal development and axon outgrowth/guidance. However signaling mechanisms responsible for BOC action during these processes remain unknown. In our previous studies, a multiprotein complex containing BOC and a closely related protein CDO promotes myogenic differentiation through activation of multiple signaling pathways, including non-receptor tyrosine kinase ABL...
November 18, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27871934/v-src-induced-nuclear-localization-of-yap-is-involved-in-multipolar-spindle-formation-in-tetraploid-cells
#8
Keiko Kakae, Masayoshi Ikeuchi, Takahisa Kuga, Youhei Saito, Naoto Yamaguchi, Yuji Nakayama
The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events, including cell division. We have reported that v-Src, which is a mutant variant of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase, resulting in a furrow regression in cytokinesis and the generation of multinucleated cells. However, the effect of v-Src on mitotic spindle formation is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo abnormal cell division, in which cells separate into more than two cells...
November 18, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27865874/bromodomain-containing-protein-2-induces-insulin-resistance-via-the-mtor-akt-signaling-pathway-and-an-inflammatory-response-in-adipose-tissue
#9
Ruixin Sun, Yi Wu, Weihua Hou, Zujun Sun, Yuxiong Wang, Huanhuan Wei, Wei Mo, Min Yu
Insulin resistance is a major metabolic abnormality in a large majority of patients with type II diabetes. Bromodomain-containing protein 2 (Brd2), a transcriptional co-activator/co-repressor with switch mating type/sucrose non-fermenting (SWI/SNF)-like functions that regulates chromatin, suppresses adipocyte differentiation and regulates pancreatic β-cell biology. However, the effects of Brd2 on insulin resistance remain unknown. Here, overexpression of Brd2 in white adipose tissue of wild-type (WT) mice led to insulin resistance...
November 16, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27865873/signaling-via-g-proteins-mediates-tumorigenic-effects-of-gpr87
#10
Kristine Niss Arfelt, Suzan Fares, Alexander H Sparre-Ulrich, Gertrud M Hjortø, Lærke S Gasbjerg, Ann-Sofie Mølleskov-Jensen, Tau Benned-Jensen, Mette M Rosenkilde
G protein-coupled receptors (GPCRs) constitute a large protein family of seven transmembrane (7TM) spanning proteins that regulate multiple physiological functions. GPR87 is overexpressed in several cancers and plays a role in tumor cell survival. Here, the basal activity of GPR87 was investigated in transiently transfected HEK293 cells, revealing ligand-independent coupling to Gαi, Gαq and Gα12/13. Furthermore, GPR87 showed a ligand-independent G protein-dependent activation of the downstream transcription factors CREB, NFκB, NFAT and SRE...
November 16, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27864060/fos-1-functions-as-a-transcriptional-activator-downstream-of-the-c-elegans-jnk-homolog-kgb-1
#11
Zhe Zhang, Limeng Liu, Kwame Twumasi-Boateng, Dena H S Block, Michael Shapira
JNK proteins are conserved stress-activated MAP kinases. In C. elegans, the JNK-homolog KGB-1 plays essential roles in protection from heavy metals and protein folding stress. However, the contributions of KGB-1 are age-dependent, providing protection in larvae, but reducing stress resistance and shortening lifespan in adults. Attenuation of DAF-16 was linked to the detrimental contributions of KGB-1 in adults, but its involvement in KGB-1-dependent protection in larvae remains unclear. To characterize age-dependent contributions of KGB-1, we used microarray analysis to measure gene expression following KGB-1 activation either in developing larvae or in adults, achieved by knocking down its negative phosphatase regulator vhp-1...
November 15, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27845183/the-phosphorylation-of-metaxin-1-controls-bak-activation-during-tnf%C3%AE-induced-cell-death
#12
Elise Petit, Pierre-François Cartron, Lisa Oliver, François M Vallette
The proapoptotic protein Bak is implicated in the execution phase of apoptosis, a cell death program. Bak is essentially mitochondrial and during early steps of apoptosis undergoes conformational changes that lead to its full membrane integration in mitochondria and the subsequent liberation of pro-apoptotic mitochondrial proteins. Little is known about the partners and mechanisms implicated in the activation of Bak. We have recently shown that Bak is incorporated into a Voltage dependent anionic channel of type 2 (VDAC2)/Metaxin 1(Mtx1)/Metaxin 2 (Mtx2) multi-protein complex in both resting and dying cells...
November 11, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27838374/cellular-defects-by-deletion-of-ano10-are-due-to-deregulated-local-calcium-signaling
#13
Podchanart Wanitchakool, Jiraporn Ousingsawat, Lalida Sirianant, Inês Cabrita, Diana Faria, Rainer Schreiber, Karl Kunzelmann
TMEM16K (ANO10) belongs to a family of ion channels and phospholipid scramblases. Mutations in ANO10 cause neurological and immunological defects, and abrogated ion transport. Here we show that Ano10 knockout in epithelial cells leads to defective ion transport, attenuated volume regulation and deranged Ca(2+) signaling. Intestinal epithelial cells from Ano10 null mice are reduced in size and demonstrate an almost abolished spontaneous and TNFα-induced apoptosis. Similar defects were found in mouse peritoneal Ano10 null macrophages and in human THP1 macrophages with reduced ANO10 expression...
November 10, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27838375/class-i-histone-deacetylases-regulate-p53-nf-%C3%AE%C2%BAb-crosstalk-in-cancer-cells
#14
Claudia Schäfer, Anja Göder, Mandy Beyer, Nicole Kiweler, Nisintha Mahendrarajah, Anke Rauch, Teodora Nikolova, Natasa Stojanovic, Martin Wieczorek, Thomas R Reich, Maja T Tomicic, Michael Linnebacher, Jürgen Sonnemann, Sascha Dietrich, Andreas Sellmer, Siavosh Mahboobi, Thorsten Heinzel, Günter Schneider, Oliver H Krämer
The transcription factors NF-κB and p53 as well as their crosstalk determine the fate of tumor cells upon therapeutic interventions. Replicative stress and cytokines promote signaling cascades that lead to the co-regulation of p53 and NF-κB. Consequently, nuclear p53/NF-κB signaling complexes activate NF-κB-dependent survival genes. The 18 histone deacetylases (HDACs) are epigenetic modulators that fall into four classes (I-IV). Inhibitors of histone deacetylases (HDACi) become increasingly appreciated as anti-cancer agents...
November 9, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27836739/docosahexaenoic-acid-signaling-attenuates-the-proliferation-and-differentiation-of-bone-marrow-derived-osteoclast-precursors-and-promotes-apoptosis-in-mature-osteoclasts
#15
Hyun-Ju Kim, Boram Ohk, Hye Jin Yoon, Woo Youl Kang, Sook Jin Seong, Shin-Yoon Kim, Young-Ran Yoon
Docosahexaenoic acid (DHA), a component of omega-3 fatty acids, has been reported to protect against inflammatory bone diseases such as osteoporosis and rheumatoid arthritis. However, its exact mechanism in bone resorbing cells has not been elucidated. In this study, we investigated the effects and the molecular mechanism of DHA on the proliferation, differentiation, and survival of osteoclast lineage cells using mouse bone marrow-derived macrophages (BMMs). DHA suppressed the macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursors, BMMs, in a dose-dependent manner...
November 9, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27836738/blocking-inhibition-to-yap-by-actinomycind-enhances-anti-tumor-efficacy-of-corosolic-acid-in-treating-liver-cancer
#16
Yanfeng Xu, Yinghui Zhao, Yanli Xu, Yu Guan, Xiao Zhang, Yan Chen, Qi Wu, Guoqing Zhu, Yuxin Chen, Fenyong Sun, Jiayi Wang, Yongchun Yu
Chemotherapy is critical for the treatment of liver cancer. Despite the pro-apoptotic effects of corosolic acid (CA) have been revealed, the methods to enhance its efficacy are unclear. The aim of this study is to investigate the target that might reduce CA efficacy and figure out the way to conquer it. We found reduction of Yes-associated protein (YAP) might be a critical event that suppresses efficacy of CA. Treatment of CA accelerated degradation of YAP via enhancing its phosphorylation by LATS1. Moreover, we found CA boosts βTrCP-dependent Ubiquitination of YAP...
November 9, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27832964/spatiotemporal-dynamics-of-the-calcineurin-target-crza
#17
Patricia Hernández-Ortiz, Eduardo A Espeso
The response of Aspergilli to elevated concentrations of extracellular calcium and manganese, or environmental alkalinization is mediated by CrzA, a calcineurin-responsive transcription factor (TF). CrzA is the effector of a signaling pathway which includes the apical protein's calmodulin and calcineurin, and the protein kinases GskA and CkiA. Preferentially located in the cytoplasm, CrzA is the only element of the pathway modifying its localization under those stress conditions, being imported into nuclei...
November 8, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27826032/sterol-regulatory-element-binding-protein-srebp-1-is-a-novel-regulator-of-the-transforming-growth-factor-tgf-%C3%AE-receptor-i-t%C3%AE-ri-through-exosomal-secretion
#18
Richard Van Krieken, Guang Chen, Bo Gao, Jolene Read, Hassan A Al Saleh, Renzhong Li, Khalid Al-Nedawi, Joan C Krepinsky
Accumulation of matrix in the glomerulus is a classic hallmark of diabetic nephropathy. The profibrotic cytokine transforming growth factor beta 1 (TGF-β1) plays a central role in the development of glomerular sclerosis. Recent studies have demonstrated that the transcription factor sterol regulatory element binding protein (SREBP)-1 is an important regulator of glomerular sclerosis through both induction of TGF-β1 as well as facilitation of its signaling. Here we have identified that SREBP-1 is also a novel regulator of TGF-β receptor I (TβRI) expression in kidney mesangial cells...
November 5, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27818291/c-terminal-motif-of-human-neuropeptide-y4-receptor-determines-internalization-and-arrestin-recruitment
#19
Lizzy Wanka, Stefanie Babilon, Kerstin Burkert, Karin Mörl, Vsevolod V Gurevich, Annette G Beck-Sickinger
The human neuropeptide Y4 receptor is a rhodopsin-like G protein-coupled receptor (GPCR), which contributes to anorexigenic signals. Thus, this receptor is a highly interesting target for metabolic diseases. As GPCR internalization and trafficking affect receptor signaling and vice versa, we aimed to investigate the molecular mechanism of hY4R desensitization and endocytosis. The role of distinct segments of the hY4R carboxyl terminus was investigated by fluorescence microscopy, binding assays, inositol turnover experiments and bioluminescence resonance energy transfer assays to examine the internalization behavior of hY4R and its interaction with arrestin-3...
November 3, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27816670/two-barcodes-encoded-by-the-type-1-pdz-and-by-phospho-ser-312-regulate-retromer-wash-mediated-sorting-of-the-%C3%A3-1-adrenergic-receptor-from-endosomes-to-the-plasma-membrane
#20
Mohammed M Nooh, Suleiman W Bahouth
Recycling of the majority of agonist-internalized GPCR is dependent on a type I-PDZ "barcode" in their C-tail. The recycling of wild-type (WT) ß1-AR is also dependent on its default "type-1 PDZ barcode", but trafficking of the ß1-AR is inhibited when PKA or its substrate serine at position 312 (Ser(312)) are inactivated. We tested the hypothesis that phospho-Ser(312) provided a second barcode for ß1-AR sorting from endosomes to the plasma membrane by determining the role of retromer/WASH complexes in ß1-AR trafficking...
November 2, 2016: Cellular Signalling
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