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Protein Kinase

Xiuqing Tian, Rui Guo, Yujiao Zhang, Lingling Xu, Xianbing Liu, Yinglong Hou
OBJECTIVE: To observe the effects of sympathetic overactivity on the immune system involved in the imbalance of T helper (Th) lymphocytes, we investigated the correlation between autonomic dysregulation and the generation of regulatory T (Treg) and Th1 chemokines in patients with acute coronary syndrome (ACS). METHODS: Blood samples obtained from patients with coronary artery disease and controls were analyzed for levels of Th1 and Treg cells and their associated cytokines by flow cytometry...
October 21, 2016: Neuroimmunomodulation
Vivek Subbiah, Oliver Holmes, Kyle Gowen, Daniel Spritz, Behrang Amini, Wei-Lien Wang, Alexa B Schrock, Funda Meric-Bernstam, Ralph Zinner, Sarina Piha-Paul, Maria Zarzour, Julia A Elvin, Rachel L Erlich, David L Stockman, Jo-Anne Vergilio, James H Suh, Philip J Stephens, Vincent Miller, Jeffrey S Ross, Siraj M Ali
Malignant gastrointestinal neuroectodermal tumor (GNET) is an aggressive rare tumor, primarily occurring in young adults with frequent local-regional metastases and recurrence after local control. The tumor is characterized by the presence of EWSR1-ATF1 or EWSR1-CREB1 and immunohistochemical positivity for S-100 protein without melanocytic marker positivity. Due to poor responses to standard sarcoma regimens, GNET has a poor prognosis, and development of effective systemic therapy is desperately needed to treat these patients...
October 21, 2016: Oncology
Laura M Divine, Mai R Nguyen, Eric Meller, Riva A Desai, Batool Arif, Erinn B Rankin, Katherine H Bligard, Cherise Meyerson, Ian S Hagemann, Maria Massad, Premal H Thaker, Andrea R Hagemann, Carolyn K McCourt, Matt A Powell, David G Mutch, Katherine C Fuh
The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9...
October 13, 2016: Oncotarget
Hua-Wen Li, Tang-Bin Zou, Qing Jia, En-Qin Xia, Wen-Jun Cao, Wen Liu, Tai-Ping He, Qin Wang
BACKGROUND: Increasing evidence supports the anticancer effects of morin in vitro and in vivo. However, the role of morin-7-sulphate sodium (NaMoS), a water-soluble flavonoid derivative synthesized from morin remains unclear. The present study investigated the tumor suppression by NaMoS in mouse melanoma cells. MATERIALS AND METHODS: We synthesized the flavonoid derivative morin-7-sulphate sodium according to the method described for quercetin-sulphate derivative, and further isolated, purified and identified the compound...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sumihiro Maeda, Lennart Mucke
Lasagna-Reeves et al. (2016) demonstrate that preventing the kinase Nuak1 from phosphorylating the microtubule-associated protein tau reduces the level of potentially pathogenic tau species in brain, a novel therapeutic strategy that could help counteract Alzheimer's disease and several other neurological disorders.
October 19, 2016: Neuron
Jin Kyung Kim, Hye-Mi Lee, Ki-Sun Park, Dong-Min Shin, Tae Sung Kim, Yi Sak Kim, Hyun-Woo Suh, Soo Yeon Kim, In Soo Kim, Jin-Man Kim, Ji-Woong Son, Kyung Mok Sohn, Sung Soo Jung, Chaeuk Chung, Sang-Bae Han, Chul-Su Yang, Eun-Kyeong Jo
Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages...
October 20, 2016: Autophagy
H Jęśko, R P Strosznajder
Sirtuins (SIRT1 to -7) are unique histone deacetylases (HDACs) whose activity depends on NAD+, thus making them capable of sensing the cellular metabolic status. Sirtuins orchestrate the stress response and damage repair, and are able to modulate the course of ageing and neurodegenerative diseases. Despite their classification as HDACs, sirtuins deacetylate a vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-B, and DNA-PK (DNA-dependent protein kinase)...
2016: Folia Neuropathologica
E Matyja, W Grajkowska, K Stępień, E Naganska
Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection...
2016: Folia Neuropathologica
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
Felix Ulbrich, Kai B Kaufmann, Alexander Meske, Wolf A Lagrèze, Michael Augustynik, Hartmut Buerkle, Carlos C Ramao, Julia Biermann, Ulrich Goebel
PURPOSE: Ischemia and reperfusion injury may induce apoptosis and lead to sustained tissue damage and loss of function, especially in neuronal organs. While carbon monoxide is known to exert protective effects after various harmful events, the mechanism of carbon monoxide releasing molecules in neuronal tissue has not been investigated yet. We hypothesize that the carbon monoxide releasing molecule (CORM) ALF-186, administered after neuronal ischemia-reperfusion injury (IRI), counteracts retinal apoptosis and its involved signaling pathways and consecutively reduces neuronal tissue damage...
2016: PloS One
Ryo Kamata, Batmunkh Bumdelger, Hiroki Kokubo, Masayuki Fujii, Koichi Yoshimura, Takafumi Ishida, Mari Ishida, Masao Yoshizumi
Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture with a high mortality rate. Although eicosapentaenoic acid (EPA) has been reported to prevent AAA formation, the mechanism by which EPA works on vascular smooth muscle cells is unknown. This study aimed to investigate the mechanism by which orally-administered EPA prevents the formation of severe AAAs that develop in Osteoprotegerin (Opg) knockout (KO) mice. In the CaCl2-induced AAA model, EPA attenuated the enhanced progression of AAAs in Opg-KO mice, including the increase in aortic diameter with destruction of elastic fibers in the media...
2016: PloS One
Ruijie Liu, Hadi Khalil, Suh-Chin J Lin, Michelle A Sargent, Allen J York, Jeffery D Molkentin
Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice...
2016: PloS One
Pieter Uvin, Maarten Albersen, Ine Bollen, Maarten Falter, Emmanuel Weyne, Loes Linsen, Hanna Tinel, Peter Sandner, Trinity J Bivalacqua, Dirk Jmk De Ridder, Frank Van der Aa, Bert Brône, Koenraad Van Renterghem
OBJECTIVES: To evaluate the expression of the Rho/Rho associated protein kinase (ROCK) pathway in corpus cavernosum of patients with severe erectile dysfunction (ED) compared to healthy human corpus cavernosum, and to test the functional effects of two Rho Kinase Inhibitors (RKI) on erectile tissue of patients with severe ED, not responding to phosphodiesterase type 5 inhibitors (PDE5-i). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from individuals undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for qPCR)...
October 20, 2016: BJU International
Sang-Jin Lee, Jeongmi Hwang, Hyeon-Ju Jeong, Miran Yoo, Ga-Yeon Go, Jae-Rin Lee, Young-Eun Leem, Jong Woo Park, Dong-Wan Seo, Yong Kee Kim, Myong-Joon Hahn, Jeung-Whan Han, Jong-Sun Kang, Gyu-Un Bae
Skeletal myogenesis is coordinated by multiple signaling pathways that control cell adhesion/migration, survival and differentiation accompanied by muscle-specific gene expression. A cell surface protein Cdo is involved in cell contact-mediated promyogenic signals through activation of p38MAPK and AKT. Protein kinase C-related kinase 2 (PKN2/PRK2) is implicated in regulation of various biological processes, including cell migration, adhesion and death. It has been shown to interact with and inhibit AKT thereby inducing cell death...
October 20, 2016: Cell Death & Disease
Qiao-Li Lv, Yuan-Tao Huang, Gui-Hua Wang, Yan-Ling Liu, Jin Huang, Qiang Qu, Bao Sun, Lei Hu, Lin Cheng, Shu-Hui Chen, Hong-Hao Zhou
Emerging studies show that dysregulation of the receptor of activated protein kinase C1 (RACK1) plays a crucial role in tumorigenesis and progression of various cancers. However, the biological function and underlying mechanism of RACK1 in glioma remains poorly defined. Here, we found that RACK1 was significantly up-regulated in glioma tissues compared with normal brain tissues, being closely related to clinical stage of glioma both in mRNA and protein levels. Moreover, Kaplan-Meier analysis demonstrated that patients with high RACK1 expression had a poor prognosis (p = 0...
October 18, 2016: International Journal of Environmental Research and Public Health
Jeanne Durendale Chiadak, Tatjana Arsenijevic, Francoise Gregoire, Nargis Bolaky, Valerie Delforge, Jason Perret, Christine Delporte
Aquaglyceroporins, belonging to the family of aquaporins (AQPs), are integral plasma membrane proteins permeable to water and glycerol that have emerged as key players in obesity. The aim of this study was to investigate the expression profile of AQPs in undifferentiated and differentiated 3T3-L1 cells and to investigate the changes in expression of aquaglyceroporins in 3T3-L1 cells differentiated into adipocytes and subjected to lipopolysaccharide (LPS) mimicking inflammation occurring during obesity. Furthermore, the study aimed at identifying the signaling cascade involved in the regulation of aquaglyceroporins expression upon LPS stimulation...
October 18, 2016: International Journal of Molecular Sciences
Katherine D Shives, Aaron R Massey, Nicholas A May, Thomas E Morrison, J David Beckham
West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an (m7)GpppNm 5' cap with 2'-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown...
October 18, 2016: Viruses
Demin Cai, Mengjie Yuan, Haoyu Liu, Shifeng Pan, Wenqiang Ma, Jian Hong, Ruqian Zhao
Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets...
October 18, 2016: Nutrients
Erik Richter, Manuela Harms, Katharina Ventz, Rolf Nölker, Martin J Fraunholz, Jörg Mostertz, Falko Hochgräfe
Internalization of Staphylococcus aureus by non-professional phagocytic cells is a major suspected cause of persistent and difficult-to-treat infections, including pneumonia. In this study, we established an infection model with 16HBE14o- human bronchial epithelial cells and demonstrated internalization, escape from phagosomal clearance and intracellular replication of S. aureus HG001 within the first four hours post-infection. We used quantitative phosphoproteomics to identify characteristic signaling networks in the host at different infection stages...
October 20, 2016: Journal of Proteome Research
Xiaoye Liu, Shuangyang Ding, Peijie Shi, Richard Dietrich, Erwin Märtlbauer, Kui Zhu
Bacillus cereus is an opportunistic pathogen that often causes foodborne infectious diseases and food poisoning. Non-haemolytic enterotoxin (Nhe) is the major toxin found in almost all enteropathogenic B. cereus and B. thuringiensis isolates. However, little is known about the cellular response after Nhe triggered pore formation on cell membrane. Here we demonstrate that Nhe induced cell cycle arrest at G0 /G1 phase and provoked apoptosis in Vero cells, most likely associated with mitogen-activated protein kinase (MAPK) and death receptor pathways...
October 20, 2016: Cellular Microbiology
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