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https://www.readbyqxmd.com/read/28087633/the-abl-pathway-bifurcates-to-balance-enabled-and-rac-signaling-in-axon-patterning-in-drosophila
#1
Ramakrishnan Kannan, Jeong-Kuen Song, Tatiana Karpova, Akanni Clarke, Madhuri Shivalkar, Benjamin Wang, Lyudmila Kotlyanskaya, Irina Kuzina, Qun Gu, Edward Giniger
The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. While individual components are known, the relationships among them remain mysterious. We now use FRET measurements of pathway activity, analysis of protein localization and genetic epistasis to dissect the structure of this network in Drosophila We find that the adaptor protein Disabled stimulates Abl kinase activity. Abl suppresses the actin regulatory factor Enabled, and we find that Abl also acts through the GEF Trio to stimulate the signaling activity of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intramolecular repression of Trio GEF activity by the Trio N-terminal domain...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28078551/the-proteolysis-adaptor-nbla-binds-to-the-n-terminus-of-%C3%AE-phycocyanin-implications-for-the-mechanism-of-phycobilisome-degradation
#2
Amelia Y Nguyen, William P Bricker, Hao Zhang, Daniel A Weisz, Michael L Gross, Himadri B Pakrasi
Phycobilisome (PBS) complexes are massive light-harvesting apparati in cyanobacteria that capture and funnel light energy to the photosystem. PBS complexes are dynamically degraded during nutrient deprivation, which causes severe chlorosis, and resynthesized during nutrient repletion. PBS degradation occurs rapidly after nutrient step down, and is specifically triggered by non-bleaching protein A (NblA), a small proteolysis adaptor that facilitates interactions between a Clp chaperone and phycobiliproteins...
January 11, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28077645/herpes-simplex-virus-1-abrogates-cgas-sting-mediated-cytosolic-dna-sensing-pathway-via-its-virion-host-shutoff-protein-ul41
#3
Chenhe Su, Chunfu Zheng
: Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor capable of detecting microbial DNA and activating the adaptor protein stimulator of interferon genes (STING), leading to interferon (IFN) production and host antiviral responses. Cells exhibited reduced type I IFN production in response to cytosolic DNA in the absence of cGAS. Although cGAS/STING-mediated DNA-sensing signal is crucial for host defense against many viruses, especial for DNA viruses, few viral components have been identified to specifically target this signaling pathway...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077630/mavs-is-essential-for-primary-cd4-t-cell-immunity-but-not-for-recall-t-cell-responses-following-an-attenuated-west-nile-virus-infection
#4
Huanle Luo, Evandro Winkelmann, Guorui Xie, Rong Fang, Bi-Hung Peng, Li Li, Helen M Lazear, Slobodan Paessler, Michael S Diamond, Michael Gale, Alan D Barrett, Tian Wang
: The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral-signaling (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the NS4B-P38G vaccine...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076326/cytosolic-thumpd1-promotes-breast-cancer-cells-invasion-and-metastasis-via-the-akt-gsk3-snail-pathway
#5
Xiupeng Zhang, Guiyang Jiang, Mingfang Sun, Haijing Zhou, Yuan Miao, Mengyuan Liang, Enhua Wang, Yong Zhang
Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28072632/asc-methylation-and-interleukin-1%C3%AE-are-associated-with-aerobic-capacity-in-heart-failure
#6
Brittany Butts, Javed Butler, Sandra B Dunbar, Elizabeth Corwin, Rebecca A Gary
BACKGROUND: Aerobic capacity, as measured by peak oxygen uptake (V[Combining Dot Above]O2), is one of the most powerful predictors of prognosis in heart failure (HF). Inflammation is a key factor contributing to alterations in aerobic capacity, and interleukin (IL)-1 cytokines are implicated in this process. The adaptor protein ASC is necessary for inflammasome activation of IL-1β and IL-18. ASC expression is controlled through epigenetic modification; lower ASC methylation is associated with worse outcomes in HF...
January 9, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28072404/autophagic-membrane-delivery-through-atg9
#7
Yuchen Feng, Daniel J Klionsky
One of the key questions regarding macroautophagy/autophagy is the mechanism through which the transmembrane protein ATG9 functions in delivering membrane to the expanding phagophore, the sequestering compartment that matures into an autophagosome. In a recent study, Zhou et al. identified a novel mechanism that regulates ATG9 trafficking from the plasma membrane and trans-Golgi network, which involves two conserved sorting signals required for ATG9 interaction with the AP1/2 adaptor complex and phosphorylation of ATG9 at Tyr8 by SRC kinase and at Ser14 by ULK1 for proper function during basal and starvation-induced autophagy...
January 10, 2017: Cell Research
https://www.readbyqxmd.com/read/28069507/a-highly-versatile-adaptor-protein-for-the-tethering-of-growth-factors-to-gelatin-based-biomaterials
#8
Cyril Addi, Frédéric Murschel, Benoît Liberelle, Nesrine Riahi, Gregory De Crescenzo
: In the field of tissue engineering, the tethering of growth factors to tissue scaffolds in an oriented manner can enhance their activity and increase their half-life. We chose to investigate the capture of the basic Fibroblast Growth Factor (bFGF) and the Epidermal Growth Factor (EGF) on a gelatin layer, as a model for the functionalization of collagen-based biomaterials. Our strategy relies on the use of two high affinity interactions, that is, the one between two distinct coil peptides as well as the one occurring between a collagen-binding domain (CBD) and gelatin...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28069291/antagonizing-cytokine-mediated-jak-stat-signaling-by-porcine-reproductive-and-respiratory-syndrome-virus
#9
REVIEW
Liping Yang, Yan-Jin Zhang
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is activated by myriad cytokines, which are involved in regulation of cell growth, proliferation, differentiation, apoptosis, angiogenesis, immunity and inflammatory response. Because of its significance in immune response, JAK-STAT pathway is often targeted by pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV causes reproductive failure in sows and respiratory disease in pigs of all ages...
December 30, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/28069136/the-inflammatory-signal-adaptor-ripk3-functions-beyond-necroptosis
#10
K Moriwaki, F K-M Chan
Receptor interacting protein kinase 3 (RIPK3) is an essential serine/threonine kinase for necroptosis, a type of regulated necrosis. A variety of stimuli can cause RIPK3 activation through phosphorylation. Activated RIPK3 in turn phosphorylates and activates the downstream necroptosis executioner mixed lineage kinase domain-like (MLKL). Necroptosis is a highly inflammatory type of cell death because of the release of intracellular immunogenic contents from disrupted plasma membrane. Indeed, RIPK3-deficient mice exhibited reduced inflammation in many inflammatory disease models...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28067668/adaptor-proteins-numb-and-numbl-promote-cell-cycle-withdrawal-by-targeting-erbb2-for-degradation
#11
Maretoshi Hirai, Yoh Arita, C Jane McGlade, Kuo-Fen Lee, Ju Chen, Sylvia M Evans
Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28067313/redundant-functions-of-i-bar-family-members-irsp53-and-irtks-are-essential-for-embryonic-development
#12
Ai Mei Chou, Kai Ping Sem, Wei Jun Lam, Sohail Ahmed, Chin Yan Lim
The insulin receptor substrate of 53 kDa, IRSp53, is an adaptor protein that works with activated GTPases, Cdc42 and Rac, to modulate actin dynamics and generate membrane protrusions in response to cell signaling. Adult mice that lack IRSp53 fail to regulate synaptic plasticity and exhibit hippocampus-associated learning deficiencies. Here, we show that 60% of IRSp53 null embryos die at mid to late gestation, indicating a vital IRSp53 function in embryonic development. We find that IRSp53 KO embryos displayed pleiotropic phenotypes such as developmental delay, oligodactyly and subcutaneous edema, and died of severely impaired cardiac and placental development...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065675/altered-expression-of-irs2-and-grb2-in-demyelination-of-peripheral-neurons-implications-in-diabetic-neuropathy
#13
Mallahalli S Manu, Kuruvanthe S Rachana, Gopal M Advirao
Demyelination of the peripheral nerves and dysfunction of Schwann cells (SCs) are the chronic complications involved in the development of peripheral neuropathy among diabetic patients. Insulin signaling plays an important role in restoring the myelin proteins in diabetic peripheral neuropathy (DPN). Since insulin levels are altered in diabetes, it becomes of great interest to appreciate the role and regulation of docking and adaptor protein, how these proteins respond to variations in the levels of insulin as experienced in juvenile diabetes...
December 29, 2016: Neuropeptides
https://www.readbyqxmd.com/read/28063625/regulation-of-insulin-receptor-phosphorylation-in-the-brains-of-prenatally-stressed-rats-new-insight-into-the-benefits-of-antidepressant-drug-treatment
#14
Katarzyna Głombik, Joanna Ślusarczyk, Ewa Trojan, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
A growing body of evidence supports the involvement of disturbances in the brain insulin pathway in the pathogenesis of depression. On the other hand, data concerning the impact of antidepressant drug therapy on brain insulin signaling remain scare and insufficient. We determinated the influence of chronic treatment with antidepressant drugs (imipramine, fluoxetine and tianeptine) on the insulin signaling pathway of the brain of adult prenatally stressed rats. 3-month-old prenatally stressed and control rats were treated for 21 days with imipramine, fluoxetine or tianeptine (10mg/kg/day i...
January 4, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28062040/studying-the-mechanochemistry-of-processive-cytoskeletal-motors-with-an-optical-trap
#15
V Belyy, A Yildiz
Cytoskeletal motors utilize the energy stored in ATP to generate linear motion along rigid filaments. Because their enzymatic cycles are tightly coupled to the production of force and forward movement, the optical-trapping technique is uniquely suited for studying their mechanochemical cycle. Here, we discuss the practical aspects of optical trapping in connection with single-motor assays and describe three distinct experimental modes (fixed-trap, force feedback, and square wave) that are typically used to investigate the enzymatic and biophysical properties of cytoskeletal motors...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28060904/past1-modulates-drosophila-eye-development
#16
Orly Dorot, Hermann Steller, Daniel Segal, Mia Horowitz
Endocytosis is a multi-step process involving a large number of proteins, both general factors, such as clathrin and adaptor protein complexes, and unique proteins, which modulate specialized endocytic processes, like the EHD proteins. EHDs are a family of Eps15 Homology Domain containing proteins that consists of four mammalian homologs, one C. elegans, one Drosophila melanogaster and two plants orthologs. These membrane-associated proteins are involved in different steps of endocytic trafficking pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28060514/targeted-covalent-inhibition-of-grb2-sos1-interaction-through-proximity-induced-conjugation-in-breast-cancer-cells
#17
Yongsheng Yu, Yunyu Nie, Qian Feng, Jiale Qu, Rui Wang, Liming Bian, Jiang Xia
Targeted covalent inhibitors of protein-protein interactions differ from reversible inhibitors in that the former bind and covalently bond the target protein at a specific site of the target. The site specificity is the result of the proximity of two reactive groups at the bound state, for example one mild electrophile in the inhibitor and a natural cysteine in the target close to the ligand binding site. Only a few pharmaceutically relevant proteins have this structural feature. Grb2, a key adaptor protein in maintaining the ERK activity via binding Sos1 to activated RTKs, is one: the N-terminal SH3 domain of Grb2 (Grb2N-SH3) carries a unique solvent-accessible cysteine Cys32 close to its Sos1-binding site...
January 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28060381/kctd2-an-adaptor-of-cullin3-e3-ubiquitin-ligase-suppresses-gliomagenesis-by-destabilizing-c-myc
#18
Eun-Jung Kim, Sung-Hak Kim, Xiong Jin, Xun Jin, Hyunggee Kim
Cullin3 E3 ubiquitin ligase ubiquitinates a wide range of substrates through substrate-specific adaptors Bric-a-brac, Tramtrack, and Broad complex (BTB) domain proteins. These E3 ubiquitin ligase complexes are involved in diverse cellular functions. Our recent study demonstrated that decreased Cullin3 expression induces glioma initiation and correlates with poor prognosis of patients with malignant glioma. However, the substrate recognition mechanism associated with tumorigenesis is not completely understood...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28056049/asc-induces-apoptosis-via-activation-of-caspase-9-by-enhancing-gap-junction-mediated-intercellular-communication
#19
Masato Kitazawa, Shigeaki Hida, Chifumi Fujii, Shun'ichiro Taniguchi, Kensuke Ito, Tomio Matsumura, Nagisa Okada, Takashi Sakaizawa, Akira Kobayashi, Michiko Takeoka, Shin-Ichi Miyagawa
ASC (apoptosis-associated speck-like protein containing a CARD) is a key adaptor molecule of inflammasomes that mediates inflammatory and apoptotic signals. Aberrant methylation-induced silencing of ASC has been observed in a variety of cancer cells, thus implicating ASC in tumor suppression, although this role remains incompletely defined especially in the context of closely neighboring cell proliferation. As ASC has been confirmed to be silenced by abnormal methylation in HT1080 fibrosarcoma cells as well, this cell line was investigated to characterize the precise role and mechanism of ASC in tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28055014/globozoospermia-and-lack-of-acrosome-formation-in-gm130-deficient-mice
#20
Feng Han, Chunyi Liu, Lianjun Zhang, Min Chen, Yang Zhou, Yan Qin, Yaqing Wang, Min Chen, Shuguang Duo, Xiuhong Cui, Shilai Bao, Fei Gao
Globozoospermia is a common reproductive disorder that causes male infertility in humans, and the malformation or loss of acrosomes is the prominent feature of this disease. Although the acrosome is thought to be derived from the Golgi apparatus, the detailed molecular mechanisms remain unclear. GM130 is a cis-side localized Golgi matrix protein,whereas the physiological functions of this protein remain elusive. Here we showed that inactivation of GM130-caused male infertility in mouse model. The primary defects were the absence of acrosomes, round sperm heads, and aberrant assembly of the mitochondrial sheath, which comprise the characteristic features of human globozoospermia...
January 5, 2017: Cell Death & Disease
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