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Adaptor protein 2

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https://www.readbyqxmd.com/read/28321204/a-comprehensive-view-of-the-%C3%AE-arrestinome
#1
Pascale Crépieux, Anne Poupon, Nathalie Langonné-Gallay, Eric Reiter, Javier Delgado, Martin H Schaefer, Thomas Bourquard, Luis Serrano, Christina Kiel
G protein-coupled receptors (GPCRs) are membrane receptors critically involved in sensing the environment and orchestrating physiological processes. As such, they transduce extracellular signals such as hormone, neurotransmitters, ions, and light into an integrated cell response. The intracellular trafficking, internalization, and signaling ability of ligand-activated GPCRs are controlled by arrestins, adaptor proteins that they interact with upon ligand binding. β-arrestins 1 and 2 in particular are now considered as hub proteins assembling multiprotein complexes to regulate receptor fate and transduce diversified cell responses...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28318976/assembly-of-cns-nodes-of-ranvier-in-myelinated-nerves-is-promoted-by-the-axon-cytoskeleton
#2
Veronica Brivio, Catherine Faivre-Sarrailh, Elior Peles, Diane L Sherman, Peter J Brophy
Nodes of Ranvier in the axons of myelinated neurons are exemplars of the specialized cell surface domains typical of polarized cells. They are rich in voltage-gated sodium channels (Nav) and thus underpin rapid nerve impulse conduction in the vertebrate nervous system [1]. Although nodal proteins cluster in response to myelination, how myelin-forming glia influence nodal assembly is poorly understood. An axoglial adhesion complex comprising glial Neurofascin155 and axonal Caspr/Contactin flanks mature nodes [2]...
March 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28316375/torilin-inhibits-inflammation-by-limiting-tak1-mediated-map-kinase-and-nf-%C3%AE%C2%BAb-activation
#3
Mehari Endale, Tae-Hwan Kim, Yi-Seong Kwak, Na-Mi Kim, Seung-Hyung Kim, Jae Youl Cho, Bong-Sik Yun, Man-Hee Rhee
Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28315351/-3-h-bmt-046091-a-potent-and-selective-radioligand-to-determine-aak1-distribution-and-target-engagement
#4
Justin V Louis, Yifeng Lu, Rick Pieschl, Yung Tian, Yang Hong, Kumaran Dandapani, Sreenivasulu Naidu, Reeba K Vikramadithyan, Carolyn Dzierba, Sarat Kumar Sarvasiddhi, Susheel J Nara, Joanne Bronson, John E Macor, Charlie Albright, Walter Kostich, Yu-Wen Li
Adaptor-associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of serine/threonine kinases, plays a role in modulating clatherin coated endocytosis of specific surface receptors. We have demonstrated that AAK1 inhibitors are efficacious in rodent models of neuropathic pain (Kostich et al., 2016). Here we have characterized the binding properties and distribution pattern of the tritiated AAK1 radioligand, [(3)H]BMT-046091, in rodents and cynomolgus monkeys, and used the radioligand to measure the brain target occupancy following systemic administration of AAK1 inhibitors...
March 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28299574/physiological-and-pathological-roles-of-15-deoxy-%C3%AE-12-14-prostaglandin-j2-in-the-central-nervous-system-and-neurological-diseases
#5
REVIEW
Tatsurou Yagami, Yasuhiro Yamamoto, Hiromi Koma
Prostaglandins (PGs) are divided into conventional PGs, e.g., PGD2, and cyclopentenone-type PGs, e.g., 15-deoxy-Δ(12,14) prostaglandin J2 (15d-PGJ2). PGD2 is non-enzymatically metabolized to PGJ2, Δ(12)-PGJ2, and 15d-PGJ2. In the central nervous system, 15d-PGJ2 differentiates embryonic midbrain cells into dopaminergic neuronal cells via its nuclear peroxysome proliferator-activated receptor-γ (PPARγ). 15d-PGJ2 exerts conflict actions: proinflammatory and anti-inflammatory activities. In the brain, 15d-PGJ2 possesses opposite functions as a neuroprotectant at low concentrations and a neurotoxicant at high concentrations in the brain...
March 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28296542/the-autophagy-machinery-restrains-inkt-cell-activation-through-cd1d1-internalization
#6
Christian W Keller, Monica Loi, Svenja Ewert, Isaak Quast, Romina Theiler, Monique Gannagé, Christian Münz, Gennaro De Libero, Stefan Freigang, Jan D Lünemann
Invariant natural killer T (iNKT) cells are innate T cells with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT-cell-activating glycolipids are currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about the mechanisms that control CD1D antigen presentation and iNKT cell activation in vivo. CD1D molecules survey endocytic pathways to bind lipid antigens in MHC class II containing compartments (MIICs) before recycling to the plasma membrane...
March 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28295715/grb7-protein-ra-domain-oligomerization
#7
Malika P Godamudunage, Albert Foster, Darius Warren, Barbara A Lyons
The growth factor receptor bound protein 7 (Grb7) is an adaptor protein that is often coamplified with the erythroblastosis oncogene B 2 receptor in 20% to 30% of breast cancer patients. Grb7 overexpression has been linked to increased cell migration and cancer metastasis. The ras associating and pleckstrin homology domain region of Grb7 has been reported to interact with various other downstream signaling proteins such as four and half Lin11, Isl-1, Mec-3 (LIM) domains isoform 2 and filamin α. These interactions are believed to play a role in regulating Grb7-mediated cell migration function...
March 14, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28288818/3-o-z-coumaroyloleanolic-acid-overcomes-cks1b-induced-chemoresistance-in-lung-cancer-by-inhibiting-hsp90-and-mek-pathways
#8
He Wang, Mingna Sun, Jiayi Guo, Lei Ma, Hui Jiang, Liang Gu, Huaying Wen, Siyan Liao, Jingqi Chen, Bohang Zeng, Yongmei Li, Yueshan Li, Xiyong Yu, Yinghong Feng, Yi Zhou
Expression of CDC28 protein kinase regulatory subunit 1 (Cks1), an adaptor for cyclin-dependent kinases, is tightly regulated at transcriptional and posttranslational levels. Increased expression of Cks1 has been documented to be attributable to cancer progression, chemoresistance, and chemosensitivity. Here we report that ectopic overexpression of Cks1b in human lung cancer cells (Cks1b-OE) induces chemoresistance of the cells to cisplatin (CDDP) and doxorubicin (DOX) through mechanisms independent of its canonical Skp2-p27 pathway...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28288669/implication-of-overexpression-of-dishevelled-associated-activator-of-morphogenesis-1-daam-1-for-the-pathogenesis-of-human-idiopathic-pulmonary-arterial-hypertension-ipah
#9
Shun Yanai, Megumi Wakayama, Haruo Nakayama, Minoru Shinozaki, Hisayuki Tsukuma, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Kazutoshi Shibuya
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis. Evidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell polarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins-namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated activator of morphogenesis 1 (Daam-1)-in pulmonary arteries...
March 14, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28286874/investigation-of-the-adaptor-protein-plic-2-in-multiple-pathways
#10
Khiem Nguyen, Robbins Puthenveetil, Olga Vinogradova
PLIC, Protein Linking IAP (CD47) to Cytoskeleton, have long since been implicated in connecting the extracellular membrane to the intracellular cell cytoskeleton. This phenomenon is supposedly achieved by bridging a receptor protein CD47 to vimentin, an intermediate filament, which in turn regulates integrin dependent cell spreading. Since the discovery of these proteins, the molecular details of the above-mentioned interactions and the underlying complexes are yet to be characterized. Several independent studies have together emphasized PLIC/Ubiquilin's role in the proteasomal degradation pathway...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28284325/expression-of-gulp1-in-bronchial-epithelium-is-associated-with-the-progression-of-emphysema-in-chronic-obstructive-pulmonary-disease
#11
Sayantan Datta, Hae-Seong Nam, Masamichi Hayashi, Leonel Maldonado, Rachel Goldberg, Mariana Brait, David Sidransky, Peter Illei, Alex Baras, Neeraj Vij, Mohammad O Hoque
BACKGROUND: GULP1 functions as a cytoplasmic adaptor protein involved in the engulfment of apoptotic cells. The aim of this study was to investigate the expression and/or promoter methylation of GULP1 in the bronchial tissue and the lung parenchyma of chronic obstructive pulmonary disease (COPD) patients and control subjects without COPD (non-smokers and smokers). METHODS: Using a case-control design, we selected a group of 15 subjects with non-small cell lung carcinoma (NSCLC), 15 subjects with COPD, 9 subjects of without COPD (4 non-smokers and 5 smokers) as controls...
March 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28282921/biglycan-and-sphingosine-kinase-1-signaling-crosstalk-regulates-the-synthesis-of-macrophage-chemoattractants
#12
Louise Tzung-Harn Hsieh, Madalina-Viviana Nastase, Heiko Roedig, Jinyang Zeng-Brouwers, Chiara Poluzzi, Stephanie Schwalm, Christian Fork, Claudia Tredup, Ralf P Brandes, Malgorzata Wygrecka, Andrea Huwiler, Josef Pfeilschifter, Liliana Schaefer
In its soluble form, the extracellular matrix proteoglycan biglycan triggers the synthesis of the macrophage chemoattractants, chemokine (C-C motif) ligand CCL2 and CCL5 through selective utilization of Toll-like receptors (TLRs) and their adaptor molecules. However, the respective downstream signaling events resulting in biglycan-induced CCL2 and CCL5 production have not yet been defined. Here, we show that biglycan stimulates the production and activation of sphingosine kinase 1 (SphK1) in a TLR4- and Toll/interleukin (IL)-1R domain-containing adaptor inducing interferon (IFN)-β (TRIF)-dependent manner in murine primary macrophages...
March 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28274878/crystal-structures-of-the-ubx-domain-of-human-ubxd7-and-its-complex-with-p97-atpase
#13
Zhi-Hui Li, Yong Wang, Min Xu, Tao Jiang
In humans, UBXD7 (also called UBXN7), an adaptor of p97 ATPase, can participate in the degradation of misfolded or damaged proteins in the p97-mediated ubiquitin proteasome system (UPS). UBXD7 binds to ubiquitinated substrates via its UBA domain and interacts with p97 N-terminal domain through its UBX domain to recruit p97 or the p97 core complex (p97/NPL4/UFD1). Here, we report the crystal structures of the UBX domain of UBXD7 (UBXD7(UBX)) at 2.0 Å resolution and its complex with p97 N-terminal domain (p97(NTD)-UBXD7(UBX) complex) at 2...
March 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28266544/misrouting-of-v-atpase-subunit-v0a1-dysregulates-lysosomal-acidification-in-a-neurodegenerative-lysosomal-storage-disease-model
#14
Maria B Bagh, Shiyong Peng, Goutam Chandra, Zhongjian Zhang, Satya P Singh, Nagarajan Pattabiraman, Aiyi Liu, Anil B Mukherjee
Defective lysosomal acidification contributes to virtually all lysosomal storage disorders (LSDs) and to common neurodegenerative diseases like Alzheimer's and Parkinson's. Despite its fundamental importance, the mechanism(s) underlying this defect remains unclear. The v-ATPase, a multisubunit protein complex composed of cytosolic V1-sector and lysosomal membrane-anchored V0-sector, regulates lysosomal acidification. Mutations in the CLN1 gene, encoding PPT1, cause a devastating neurodegenerative LSD, INCL...
March 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28263976/nlrp1-promotes-tumor-growth-by-enhancing-inflammasome-activation-and-suppressing-apoptosis-in-metastatic-melanoma
#15
Z Zhai, W Liu, M Kaur, Y Luo, J Domenico, J M Samson, Y G Shellman, D A Norris, C A Dinarello, R A Spritz, M Fujita
Inflammasomes are mediators of inflammation, and constitutively activated NLRP3 inflammasomes have been linked to interleukin-1β (IL-1β)-mediated tumorigenesis in human melanoma. Whereas NLRP3 regulation of caspase-1 activation requires the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)), caspase-1 activation by another danger-signaling sensor NLRP1 does not require ASC because NLRP1 contains a C-terminal CARD domain that facilitates direct caspase-1 activation via CARD-CARD interaction...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28259707/clinical-and-molecular-phenotyping-of-a-child-with-hermansky-pudlak-syndrome-7-an-uncommon-genetic-type-of-hps
#16
Melanie M Bryan, Nathanial J Tolman, Karen L Simon, Marjan Huizing, Robert B Hufnagel, Brian P Brooks, Vladislav Speransky, James C Mullikin, William A Gahl, May Christine V Malicdan, Bernadette R Gochuico
PURPOSE: Hermansky-Pudlak syndrome (HPS) is a rare inherited disorder with ten reported genetic types; each type has defects in subunits of either Adaptor Protein-3 complex or Biogenesis of Lysosome-related Organelles Complex (BLOC)-1, -2, or -3. Very few patients with BLOC-1 deficiency (HPS-7, -8, and -9 types) have been diagnosed. We report results of comprehensive clinical testing and molecular analyses of primary fibroblasts from a new case of HPS-7. RESULTS: A 6-year old Paraguayan male presented with hypopigmentation, ocular albinism, nystagmus, reduced visual acuity, and easy bruising...
February 27, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28244955/plasma-soluble-cd163-is-associated-with-postmortem-brain-pathology-in-human-immunodeficiency-virus-infection
#17
Alex K Bryant, David J Moore, Tricia H Burdo, Jessica R Lakritz, Ben Gouaux, Virawudh Soontornniyomkij, Cristian L Achim, Eliezer Masliah, Igor Grant, Andrew J Levine, Ronald J Ellis
OBJECTIVE: Higher plasma soluble CD163 (sCD163), shed by monocytes and macrophages, correlates with neurocognitive impairment in human immunodeficiency virus (HIV) infection. We hypothesized that higher antemortem plasma or cerebrospinal fluid sCD163 would be associated with greater postmortem neurodegeneration and/or microgliosis. DESIGN: Retrospective, postmortem observational study. METHODS: We measured sCD163 levels in antemortem plasma (n = 54) and cerebrospinal fluid (n = 32) samples from 74 HIV participants (median 5 months before death) who donated their brains to research at autopsy...
February 27, 2017: AIDS
https://www.readbyqxmd.com/read/28236763/palmatine-inhibits-trif-dependent-nf-%C3%AE%C2%BAb-pathway-against-inflammation-induced-by-lps-in-goat-endometrial-epithelial-cells
#18
Baoqi Yan, Dongsheng Wang, Shuwei Dong, Zhangrui Cheng, Lidong Na, Mengqi Sang, Hongzao Yang, Zhiqiang Yang, Shidong Zhang, Zuoting Yan
Palmatine, a natural pharmaceutical drug, possesses many biological activities. But its clinical application is rarely reported in the veterinary medicine. The aim of this study was to investigate the anti-inflammatory effects of palmatine on lipopolysaccharide (LPS)-induced inflammation in goat endometrial epithelial cells (gEECs), and the possible molecular mechanisms. Palmatine cell toxicity was determined by MTT assay, and the production of inflammatory cytokine in the cultured medium was measured with ELISA, qRT-PCR and Western blotting...
February 21, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28223944/il-1%C3%AE-induced-downregulation-of-the-multifunctional-pdz-adaptor-pdzk1-is-attenuated-by-erk-inhibition-rxr%C3%AE-or-ppar%C3%AE-stimulation-in-enterocytes
#19
Min Luo, Sunil Yeruva, Yongjian Liu, Giriprakash Chodisetti, Brigitte Riederer, Manoj B Menon, Keisuke Tachibana, Takefumi Doi, Ursula E Seidler
Background: The PDZ adaptor protein PDZK1 modulates the membrane expression and function of a variety of intestinal receptors and ion/nutrient transporters. Its expression is strongly decreased in inflamed intestinal mucosa of mice and IBD patients. Aim and Methods: We investigated whether the inflammation-associated PDZK1 downregulation is a direct consequence of proinflammatory cytokine release by treating intestinal Caco-2BBE cells with TNF-α, IFN-γ, and IL-1β, and analysing PDZK1 promotor activity, mRNA and protein expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28216678/the-cul3-spop-daxx-axis-is-a-novel-regulator-of-vegfr2-expression-in-vascular-endothelial-cells
#20
Tomohisa Sakaue, Iori Sakakibara, Takahiro Uesugi, Ayako Fujisaki, Koh-Ichi Nakashiro, Hiroyuki Hamakawa, Eiji Kubota, Takashi Joh, Yu-Ki Imai, Hironori Izutani, Shigeki Higashiyama
Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively...
February 20, 2017: Scientific Reports
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