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Adaptor protein 2

Hui-Ju Tsai, Ching-Ping Tseng
Multiple functions of platelets in various physiological and pathological conditions have prompted considerable attention on understanding how platelets are generated and activated. Of the adaptor proteins that are expressed in megakaryocytes and platelets, Disabled-2 (Dab2) has been demonstrated in the past decades as a key regulator of platelet signaling. Dab2 has two alternative splicing isoforms p82 and p59. However, the mode of Dab2's action remains to be clearly defined. In this review, we highlight the current understanding of Dab2 expression and function in megakaryocytic differentiation, platelet activation and integrin signaling...
2016: Thrombosis Journal
Aruna Nambirajan, Mehar C Sharma, Madhu Rajeshwari, Aanchal Kakkar, Vaishali Suri, Chitra Sarkar
Ependymomas are gliomas that recapitulate normal ependymal cells. The epithelial membrane antigen (EMA) shows "dot-like" and "ring-like" staining patterns, highlighting "microlumens" or intracytoplasmic rosettes, a pathognomonic ultrastructural feature. NHERF1/EBP50, an adaptor protein localized at the apical plasma membrane of human epithelia, has been found to localize to these microlumens. We aimed to analyze the staining patterns of EMA and EBP50 in ependymomas and other tumors, and thereby compare their diagnostic utility...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Nurbek Mambetsariev, Wai W Lin, Alicia M Wallis, Laura L Stunz, Gail A Bishop
The adaptor protein TNF receptor-associated factor 3 (TRAF3) is a critical regulator of B lymphocyte survival. B cell-specific TRAF3 deficiency results in enhanced viability and is associated with development of lymphoma and multiple myeloma. We show that TRAF3 deficiency led to induction of two proteins important for glucose metabolism, Glut1 and Hexokinase 2 (HXK2). This was associated with increased glucose uptake. In the absence of TRAF3, anaerobic glycolysis and oxidative phosphorylation were increased in B cells without changes in mitochondrial mass or reactive oxygen species...
October 18, 2016: Scientific Reports
Wei-Shan Hung, Pin Ling, Ju-Chien Cheng, Shy-Shin Chang, Ching-Ping Tseng
Toll-like receptor 4 (TLR4) plays a pivotal role in the host response to lipopolysaccharide (LPS), a major cell wall component of Gram-negative bacteria. Here, we elucidated whether the endocytic adaptor protein Disabled-2 (Dab2), which is abundantly expressed in macrophages, plays a role in LPS-stimulated TLR4 signaling and trafficking. Molecular analysis and transcriptome profiling of RAW264.7 macrophage-like cells expressing short-hairpin RNA of Dab2 revealed that Dab2 regulated the TLR4/TRIF pathway upon LPS stimulation...
October 17, 2016: Scientific Reports
Marlen Thiere, Stefanie Kliche, Bettina Müller, Jan Teuber, Isabell Nold, Oliver Stork
Integrin-mediated cell adhesion and signaling is of critical importance for neuronal differentiation. Recent evidence suggests that an "inside-out" activation of β1-integrin, similar to that observed in hematopoietic cells, contributes to the growth and branching of dendrites. In this study, we investigated the role of the hematopoietic adaptor protein adhesion and degranulation promoting adapter protein (ADAP) in these processes. We demonstrate the expression of ADAP in the developing and adult nervous hippocampus, and in outgrowing dendrites of primary hippocampal neurons...
2016: Frontiers in Molecular Neuroscience
Yu Chen, Xiaoling Deng, Junfang Deng, Jiehua Zhou, Yuping Ren, Shengxuan Liu, Deborah J Prusak, Thomas G Wood, Xiaoyong Bao
Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion...
October 13, 2016: Virology
Elvira Khialeeva, Ellen M Carpenter
The reelin signaling pathway has been established as an important regulator of cell migration during development of the central nervous system, and disruptions in reelin signaling alter the positioning of many types of neurons in the developing central nervous system. Reelin is a large extracellular matrix glycoprotein and governs cell migration through activation of multiple intracellular signaling events via the receptors ApoE receptor 2 (ApoER2) and Very Low Density Lipoprotein Receptor (VLDLR), and the intracellular adaptor protein Disabled-1 (Dab1)...
October 14, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Junsheng Li, Barbara Kwiatkowska, Hao Lu, Maren Voglstätter, Erika Ueda, Michael Grunze, Jonathan Sleeman, Pavel A Levkin, Irina Nazarenko
Malignant transformation is associated with enhancement of cell plasticity, which allows cancer cells to survive under different conditions by adapting to their microenvironment during growth and metastatic spread. Much effort has been devoted to understanding the molecular mechanisms of these processes. Although the importance of the extracellular matrix and of surface properties in these mechanisms is evident, the direct impact of distinct physical and chemical surfaces characteristics on cell fate remains unclear...
October 12, 2016: ACS Applied Materials & Interfaces
Xinchun Ye, Delian Kong, Jun Wang, Tauheed Ishrat, Hongjuan Shi, Xiaohui Ding, Guiyun Cui, Fang Hua
Myeloid differentiation primary-response protein-88 (MyD88) is one of adaptor proteins mediating Toll-like receptors (TLRs) signaling. Activation of MyD88 results in the activation of nuclear factor kappa B (NFκB) and the increase of inflammatory responses. Evidences have demonstrated that TLRs signaling contributes to cerebral ischemia/reperfusion (I/R) injury. However, the role of MyD88 in this mechanism of action is disputed and needs to be clarified. In the present study, in a mouse model of cerebral I/R, we examined the activities of NFκB and interferon factor-3 (IRF3), and the inflammatory responses in ischemic brain tissue using ELISA, Western blots, and real-time PCR...
October 4, 2016: Biochemical and Biophysical Research Communications
Gaurav Shrivastava, Moisés León-Juárez, Julio García-Cordero, David Eduardo Meza-Sánchez, Leticia Cedillo-Barrón
A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1...
October 3, 2016: Immunologic Research
Tatsuro Iso, Takafumi Suzuki, Liam Baird, Masayuki Yamamoto
The transcription factor Nrf2 (NF-E2-related-factor-2) is essential for the oxidative and electrophilic stress responses. Keap1 (Kelch-like-ECH-associated-protein-1), an adaptor for a Cullin-3 (Cul3)-based ubiquitin ligase, regulates Nrf2 activity through proteasomal degradation, and acts as a sensor for oxidative and electrophilic stresses. The Keap1-Cul3 complex is a critical regulator of the cellular Nrf2 level, yet quantitative information regarding their endogenous intracellular concentrations in homeostatic conditions and during stress responses is unknown...
October 3, 2016: Molecular and Cellular Biology
Youngmin Park, Zheng-Yi Xu, Soo Youn Kim, Jihyeong Lee, Bongsoo Choi, Juhun Lee, Hyeran Kim, Hee-Jung Sim, Inhwan Hwang
The phytohormone abscisic acid (ABA) plays crucial roles in various physiological processes, including responses to abiotic stresses, in plants. Recently, multiple ABA transporters were identified. The loss-of-function and gain-of-function mutants of these transporters show altered ABA sensitivity and stomata regulation, highlighting the importance of ABA transporters in ABA-mediated processes. However, how the activity of these transporters is regulated remains elusive. Here, we show that spatial regulation of ABCG25, an ABA exporter, is an important mechanism to control its activity...
October 3, 2016: Plant Cell
Arpita Sen, Ligia Acosta-Sampson, Christopher G Alvaro, Jonathan S Ahn, Jamie H D Cate, Jeremy Thorner
: When expressed in Saccharomyces cerevisiae using either of two constitutive yeast promoters (PGK1prom and CCW12prom), the transporters CDT-1 and CDT-2 from the filamentous fungus Neurospora crassa are able to catalyze, respectively, active transport and facilitated diffusion of cellobiose (and, for CDT-2, also xylan and its derivatives). In S. cerevisiae, endogenous permeases are removed from the plasma membrane by clathrin-mediated endocytosis and are marked for internalization through ubiquitinylation catalyzed by Rsp5, a HECT class ubiquitin:protein ligase (E3)...
September 30, 2016: Applied and Environmental Microbiology
Nina Tang, Juan Ma, Ke Si Wang, Chunliu Mi, Ying Lv, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Jung Joon Lee, Xuejun Jin
Nuclear factor-kappa B (NF-κB) has been reported to play a pivotal role in many physiological processes including inflammation, apoptosis, and angiogenesis. We discovered a potent natural NF-κB inhibitor, dihydromyricetin, from the traditional herb Ampelopsis grossedentata, which has a long history of use in food and medicine. In this study, we demonstrated the effect of dihydromyricetin on NF-κB activation in TNF-α-induced HeLa cells. Dihydromyricetin was found to markedly inhibit the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and subsequent nuclear translocation of p65...
November 2016: Molecular and Cellular Biochemistry
Giada Zurlo, Jianping Guo, Mamoru Takada, Wenyi Wei, Qing Zhang
Protein hydroxylation is a post-translational modification catalyzed by 2-oxoglutarate-dependent dioxygenases. The hydroxylation modification can take place on various amino acids, including but not limited to proline, lysine, asparagine, aspartate and histidine. A classical example of this modification is hypoxia inducible factor alpha (HIF-α) prolyl hydroxylation, which affects HIF-α protein stability via the Von-Hippel Lindau (VHL) tumor suppressor pathway, a Cullin 2-based E3 ligase adaptor protein frequently mutated in kidney cancer...
September 20, 2016: Biochimica et Biophysica Acta
Fadil M Hannan, Valerie N Babinsky, Rajesh V Thakker
The extracellular calcium (Ca(2+) o)-sensing receptor (CaSR) is a family C G protein-coupled receptor, which detects alterations in Ca(2+) o concentrations and modulates parathyroid hormone secretion and urinary calcium excretion. The central role of the CaSR in Ca(2+) o homeostasis has been highlighted by the identification of mutations affecting the CASR gene on chromosome 3q21.1. Loss-of-function CASR mutations cause familial hypocalciuric hypercalcaemia (FHH), whereas gain-of-function mutations lead to autosomal dominant hypocalcaemia (ADH)...
October 2016: Journal of Molecular Endocrinology
Sied Kebir, Zacharias Orfanos, Julia Schuld, Markus Linhart, Christian Lamberz, Peter F M van der Ven, Jan Schrickel, Gregor Kirfel, Dieter O Fürst, Rainer Meyer
Pressure overload induces cardiac remodeling involving both the contractile machinery and intercalated disks (IDs). Filamin C (FlnC) and Xin actin-binding repeat-containing proteins (XIRPs) are multi-adapters localizing in IDs of higher vertebrates. Knockout of the gene encoding Xin (Xirp1) in mice leads to a mild cardiac phenotype with ID mislocalization. In order to amplify this phenotype, we performed transverse aortic constriction (TAC) on control and Xirp1-deficient mice. TAC induced similar left ventricular hypertrophy in both genotypes, suggesting that the lack of Xin does not lead to higher susceptibility to cardiac overload...
October 15, 2016: Experimental Cell Research
Martha Lappas
Preventing spontaneous preterm birth is one of the most important issues facing perinatal medicine today. The pathophysiology of preterm labor, the single biggest cause of preterm birth, is poorly understood. Inflammation, however, plays a significant role in the terminal processes of human labor, which include myometrial contractions. Nuclear factor κB (NF-κB) drives the transcription of proinflammatory mediators involved in the terminal effector pathways of human labor and delivery. Recent studies in nongestational tissues have shown that the adaptor protein p62 interacts with NF-κB to induce inflammation...
September 16, 2016: Reproductive Sciences
Pei-Yu Chen, Lingfeng Qin, Guangxin Li, George Tellides, Michael Simons
Smooth muscle cells (SMCs) in normal blood vessels exist in a highly differentiate state characterized by expression of SMC-specific contractile proteins ("contractile phenotype"). Following blood vessel injury in vivo or when cultured in vitro in the presence of multiple growth factors, SMC undergo a phenotype switch characterized by the loss of contractile markers and appearance of expression of non-muscle proteins ("proliferative phenotype"). While a number of factors have been reported to modulate this process, its regulation remains uncertain...
2016: Scientific Reports
Da Hyun Lee, Dai Hoon Han, Ki Taek Nam, Jeong Su Park, Soo Hyun Kim, Milim Lee, Gyuri Kim, Byung Soh Min, Bong-Soo Cha, Yu Seol Lee, Su Haeng Sung, Haengdueng Jeong, Hye Won Ji, Moon Joo Lee, Jae Sung Lee, Hui-Young Lee, Yoomi Chun, Joungmok Kim, Masaaki Komatsu, Yong-Ho Lee, Soo Han Bae
Oxidative stress is important for the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a chronic disease that ranges from hepatic steatosis to nonalcoholic steatohepatitis (NASH). The nuclear factor erythroid 2-related factor 2-Kelch-like ECH associated protein 1 (Nrf2-Keap1) pathway is essential for cytoprotection against oxidative stress. In this study, we found that oxidative stress or inflammatory biomarkers and TUNEL positive cells were markedly increased in NASH patients compared to normal or simple steatosis...
September 12, 2016: Free Radical Biology & Medicine
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