Read by QxMD icon Read


Lisa Brenan, Aleksandr Andreev, Ofir Cohen, Sasha Pantel, Atanas Kamburov, Davide Cacchiarelli, Nicole S Persky, Cong Zhu, Mukta Bagul, Eva M Goetz, Alex B Burgin, Levi A Garraway, Gad Getz, Tarjei S Mikkelsen, Federica Piccioni, David E Root, Cory M Johannessen
Tumor-specific genomic information has the potential to guide therapeutic strategies and revolutionize patient treatment. Currently, this approach is limited by an abundance of disease-associated mutants whose biological functions and impacts on therapeutic response are uncharacterized. To begin to address this limitation, we functionally characterized nearly all (99.84%) missense mutants of MAPK1/ERK2, an essential effector of oncogenic RAS and RAF. Using this approach, we discovered rare gain- and loss-of-function ERK2 mutants found in human tumors, revealing that, in the context of this assay, mutational frequency alone cannot identify all functionally impactful mutants...
October 18, 2016: Cell Reports
Marat R Talipov, Jaladhi Nayak, Michael Lepley, Robert D Bongard, Daniel S Sem, Ramani Ramchandran, Rajendra Rathore
DUSP5 is an inducible nuclear dual-specificity phosphatase that specifically interacts with and deactivates extracellular signal-regulated kinases ERK1 and ERK2, which are responsible for cell proliferation, differentiation, and survival. The phosphatase domain (PD) of DUSP5 has unique structural features absent in other nuclear DUSPs, such as presence of a secondary anion-binding site in the proximity to the reaction center and a glutamic acid E264 positioned next to the catalytic cysteine C263, as well as a remote intra-molecular disulfide linkage...
October 14, 2016: Biochemistry
Anastasia Mylona, Francois-Xavier Theillet, Charles Foster, Tammy M Cheng, Francesc Miralles, Paul A Bates, Philipp Selenko, Richard Treisman
Multisite phosphorylation regulates many transcription factors, including the serum response factor partner Elk-1. Phosphorylation of the transcriptional activation domain (TAD) of Elk-1 by the protein kinase ERK at multiple sites potentiates recruitment of the Mediator transcriptional coactivator complex and transcriptional activation, but the roles of individual phosphorylation events had remained unclear. Using time-resolved nuclear magnetic resonance spectroscopy, we found that ERK2 phosphorylation proceeds at markedly different rates at eight TAD sites in vitro, which we classified as fast, intermediate, and slow...
October 14, 2016: Science
Darkhan Utepbergenov, Paulina M Hennig, Urszula Derewenda, Mykhaylo V Artamonov, Avril V Somlyo, Zygmunt S Derewenda
Ribosomal S6 kinases (RSK) play important roles in cell signaling through the mitogen-activated protein kinase (MAPK) pathway. Each of the four RSK isoforms (RSK1-4) is a single polypeptide chain containing two kinase domains connected by a linker sequence with regulatory phosphorylation sites. Here, we demonstrate that full-length RSK2-which is implicated in several types of cancer, and which is linked to the genetic Coffin-Lowry syndrome-can be overexpressed with high yields in Escherichia coli as a fusion with maltose binding protein (MBP), and can be purified to homogeneity after proteolytic removal of MBP by affinity and size-exclusion chromatography...
2016: PloS One
Andrew W Holle, Alistair J McIntyre, Jared Kehe, Piyumi Wijesekara, Jennifer L Young, Ludovic G Vincent, Adam J Engler
Human mesenchymal stem cells (hMSCs) receive differentiation cues from a number of stimuli, including extracellular matrix (ECM) stiffness. The pathways used to sense stiffness and other physical cues are just now being understood and include proteins within focal adhesions. To rapidly advance the pace of discovery for novel mechanosensitive proteins, we employed a combination of in silico and high throughput in vitro methods to analyze 47 different focal adhesion proteins for cryptic kinase binding sites. High content imaging of hMSCs treated with small interfering RNAs for the top 6 candidate proteins showed novel effects on both osteogenic and myogenic differentiation; Vinculin and SORBS1 were necessary for stiffness-mediated myogenic and osteogenic differentiation, respectively...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Shubin Hong, Shuang Yu, Jin Li, Yali Yin, Yujie Liu, Quan Zhang, Hongyu Guan, Yanbing Li, Haipeng Xiao
BACKGROUND: MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that play important roles in multiple biological processes. MiR-20b has been reported to be dysregulated in papillary thyroid carcinoma (PTC). However, the functional roles are still largely unknown. This study aimed to investigate the biological functions and the underlying molecular mechanisms of miR-20b in PTC. METHOD: The expression of miR-20b was assessed by quantitative RT-PCR in 47 pairs of PTC and adjacent normal thyroid tissues...
October 7, 2016: Thyroid: Official Journal of the American Thyroid Association
Xujuan Sun, Bin Wei, Shuqing Liu, Chunmei Guo, Na Wu, Qinlong Liu, Ming-Zhong Sun
OBJECTIVE: Annexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism. METHODS: RNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5- Hca-F cells were obtained via G418 screening by limited dilution method...
September 30, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jianzhong Chen
Extracellular signal-regulated kinase 2 (ERK2) is a promising target for designs and development of anticancer drugs. Molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann method were applied to study binding difference of ADP and ATP to ERK2. The results prove that the binding ability of ATP to ERK2 is stronger than that of ADP. Principal component analysis performed by using MD trajectories suggest that bindings of ADP and ATP to ERK2 change motion directions of two helixes α1 and α2...
October 3, 2016: Chemical Biology & Drug Design
Wei Lei, Yuan He, Xiaorong Shui, Guoming Li, Guosen Yan, Yu Zhang, Shian Huang, Can Chen, Yuanlin Ding
Pulmonary arterial hypertension (PAH) is characterized by endothelial dysfunction and structural remodeling of the pulmonary vasculature, mediated initially by reduced oxygen availability in the lungs. Hypoxia inducible factor (HIF), consisting of the functional subunit, HIF‑1α, and the constitutively expressed HIF‑1β, is involved in the pathological processes associated with hypoxia. In the current study, the sequences of cDNAs and amino acids of HIF were characterized and analyzed using online bioinformatics tools...
September 20, 2016: Molecular Medicine Reports
Zhiwei Ang, Jun Zhi Er, Nguan Soon Tan, Jinhua Lu, Yih-Cherng Liou, Johannes Grosse, Jeak Ling Ding
Knockout mice studies implicate the mammalian short-chain fatty acid (SCFA) receptors, FFAR2 and FFAR3- in colitis, arthritis and asthma. However, the correlation with human biology is uncertain. Here, we detected FFAR2 and FFAR3 expression in human monocytes via immunohistochemistry. Upon treatment with acetate SCFA or FFAR2- and FFAR3-specific synthetic agonists, human monocytes displayed elevated p38 phosphorylation and attenuated C5, CCL1, CCL2, GM-CSF, IL-1α, IL-1β and ICAM-1 inflammatory cytokine expression...
September 26, 2016: Scientific Reports
Gabriel Nasri Marzuca-Nassr, Kaio Fernando Vitzel, Luís Gustavo De Sousa, Gilson M Murata, Amanda Rabello Crisma, Carlos Flores Rodrigues Junior, Phablo Abreu, Rosângela Pavan Torres, Jorge Mancini-Filho, Sandro M Hirabara, Philip Newsholme, Rui Curi
The effects of either eicosapentaenoic (EPA)- or docosahexaenoic (DHA)-rich fish oils on hindlimb suspension (HS)-induced muscle disuse atrophy were compared. Daily oral supplementations (0.3 mL/100 g b.w.) with mineral oil (MO) or high EPA or high DHA fish oils were performed in adult rats. After 2 weeks, the animals were subjected to HS for further 2 weeks. The treatments were maintained alongside HS At the end of 4 weeks, we evaluated: body weight gain, muscle mass and fat depots, composition of fatty acids, cross-sectional areas (CSA) of the soleus muscle and soleus muscle fibers, activities of cathepsin L and 26S proteasome, and content of carbonylated proteins in the soleus muscle...
September 2016: Physiological Reports
Mikita M Misiura, Anatoly B Kolomeisky
ERK2 are protein kinases that during the enzymatic catalysis, in contrast to traditional enzymes, utilize additional interactions with substrates outside of the active sites. It is widely believed that these docking interactions outside of the enzymatic pockets enhance the specificity of these proteins. However, the molecular mechanisms of how the docking interactions affect the catalysis remain not well understood. Here, we develop a simple theoretical approach to analyze the enzymatic catalysis in ERK2 proteins...
October 13, 2016: Journal of Physical Chemistry. B
Wonhwa Lee, Sae-Kwang Ku, Songhee Park, Kyung-Min Kim, Hyukjae Choi, Jong-Sup Bae
The nucleosomal protein high-mobility group box-1 (HMGB1), which has recently been established as a late mediator of lethal systemic inflammation, has a relatively wide therapeutic window for pharmacological interventions. Compounds produced by marine-derived microbes have been widely investigated for their potential use as bioactive natural products. Cyclic dipeptides, which are also known as diketopiperazines, are molecules that are frequently found in marine-derived microorganisms. While their pharmacological potential has been well established, their biological activities against septic responses have not yet been reported...
2016: American Journal of Chinese Medicine
Jinyue Wang, Xiaohong Wang, Weidou Feng
OBJECTIVE: The purpose of this paper was to study the effect of transforming growth factor beta (TGFβ) signaling pathway on reloading-mediated restoration of disuse muscle loss induced by hind limb suspension in rats. DESIGN: Rats were divided into 4 groups: control group (CON), HLS group (hind limb suspension for 2 weeks), HLS + R group (hind limb suspension for 2 weeks followed by 2 weeks of natural reloading), and HRS + E group (hind limb suspension for 2 weeks followed by 2 weeks of treadmill exercise)...
September 8, 2016: American Journal of Physical Medicine & Rehabilitation
M J Erb, D Camacho, W Xie, B M Maslikowski, B Fielding, R Ghosh, F-A Poujade, M Athar, S Assee, L-E Mantella, P-A Bédard
The activation of the growth-arrest specific (gas) p20K gene depends on the interaction of C/EBPβ with two elements of a 48 bp promoter region termed the quiescence-responsive unit (QRU). Here we identify the ERK2 kinase as a transcriptional repressor of the p20K QRU in cycling chicken embryo fibroblasts. ERK2 binds to repeated GAAAG sequences overlapping the C/EBPβ sites of the QRU. The recruitment of ERK2 and C/EBPβ is mutually exclusive and dictates the expression of p20K. The C/EBP Homologous Protein CHOP is associated with C/EBPβ in conditions promoting ER stress and, to a lesser extent, in cycling CEF but is not detectable when C/EBPβ ισ immunoprecipitated from contact-inhibited cells...
September 6, 2016: Molecular and Cellular Biology
Yi-Jen Liao, Yen-Hua Lee, Fu-Ling Chang, Hsun Ho, Chin-Han Huang, Yuh-Ching Twu
BACKGROUND: Phosphorylation status of the transcription factor CCAAT/enhancer binding protein α (C/EBPα) has been demonstrated in a human hematopoietic cell model to regulate the formation of branched I antigen by affecting its binding affinity to the promoter region of the IGnTC gene during erythroid and granulocytic differentiation. STUDY DESIGN AND METHODS: The K-562 cell line was induced to differentiate into red blood cells (RBCs) or granulocytes by sodium butyrate or retinoic acid, respectively, to study the involvement of three MAP kinase pathways in I antigen synthesis...
September 7, 2016: Transfusion
Rentaro Okazaki, Toru Doi, Kentaro Hayakawa, Kazuhito Morioka, Osamu Imamura, Kunio Takishima, Makoto Hamanoue, Yasuhiro Sawada, Motoshi Nagao, Sakae Tanaka, Toru Ogata
BACKGROUND: Brain inflammation is a crucial component of demyelinating diseases such as multiple sclerosis. Although the initiation of inflammatory processes by the production of cytokines and chemokines by immune cells is well characterized, the processes of inflammatory aggravation of demyelinating diseases remain obscure. Here, we examined the contribution of Erk2, one of the isoforms of the extracellular signal-regulated kinase, to demyelinating inflammation. METHODS: We used the cuprizone-induced demyelinating mouse model...
2016: Journal of Neuroinflammation
Qingxia Kong, Xia Min, Ran Sun, Jianying Gao, Ruqing Liang, Lei Li, Xu Chu
The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor)...
September 2016: Oncology Letters
Ran Du, Jia-Lin Wang, Yan-Ling Wang
PURPOSE: To determine the molecular mechanisms underlying ocular ischemic syndrome (OIS). This study uses a rat model to evaluate the role of the RhoA/MEK1/ ERK1/2/iNOS pathways in response to OIS-associated oxidative and nitrosative stress, with a long-term goal of identifying therapeutic targets for OIS. METHODS: Rats were randomly allocated to one of three groups: bilateral occlusion of the common carotid artery (BOCCA), sham surgery control, or unoperated control (n = 8/group)...
August 18, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
Benjamin Groves, Arjun Khakhar, Cory M Nadel, Richard G Gardner, Georg Seelig
Evolution has often copied and repurposed the mitogen-activated protein kinase (MAPK) signaling module. Understanding how connections form during evolution, in disease and across individuals requires knowledge of the basic tenets that govern kinase-substrate interactions. We identify criteria sufficient for establishing regulatory links between a MAPK and a non-native substrate. The yeast MAPK Fus3 and human MAPK ERK2 can be functionally redirected if only two conditions are met: the kinase and substrate contain matching interaction domains and the substrate includes a phospho-motif that can be phosphorylated by the kinase and recruit a downstream effector...
2016: ELife
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"