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Protein Kinase

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https://www.readbyqxmd.com/read/29925063/targeting-shp-1-2-and-ship-pathways-a-novel-strategy-for-cancer-treatment
#1
REVIEW
Wolfram C M Dempke, Peter Uciechowski, Klaus Fenchel, Timothy Chevassut
Well-balanced levels of tyrosine phosphorylation, maintained by the reversible and coordinated actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), are critical for a wide range of cellular processes including growth, differentiation, metabolism, migration, and survival. Aberrant tyrosine phosphorylation, as a result of a perturbed balance between the activities of PTKs and PTPs, is linked to the pathogenesis of numerous human diseases, including cancer, suggesting that PTPs may be innovative molecular targets for cancer treatment...
June 20, 2018: Oncology
https://www.readbyqxmd.com/read/29925000/the-pp2a-like-protein-phosphatase-ppg1-and-the-far-complex-cooperatively-counteract-ck2-mediated-phosphorylation-of-atg32-to-inhibit-mitophagy
#2
Kentaro Furukawa, Tomoyuki Fukuda, Shun-Ichi Yamashita, Tetsu Saigusa, Yusuke Kurihara, Yutaka Yoshida, Hiromi Kirisako, Hitoshi Nakatogawa, Tomotake Kanki
Mitophagy plays an important role in mitochondrial quality control. In yeast, phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 (CK2) upon induction of mitophagy is a prerequisite for interaction of Atg32 with Atg11 (an adaptor protein for selective autophagy) and following delivery of mitochondria to the vacuole for degradation. Because CK2 is constitutively active, Atg32 phosphorylation must be precisely regulated to prevent unrequired mitophagy. We found that the PP2A (protein phosphatase 2A)-like protein phosphatase Ppg1 was essential for dephosphorylation of Atg32 and inhibited mitophagy...
June 19, 2018: Cell Reports
https://www.readbyqxmd.com/read/29924982/a-modified-pectic-polysaccharide-from-turmeric-curcuma-longa-with-antiulcer-effects-via-anti-secretary-mucoprotective-and-il-10-mediated-anti-inflammatory-mechanisms
#3
Harsha Mysore Rajagopal, Srikanta Belagihalli Manjegowda, Chandraprakash Serkad, Shylaja Mallaiah Dharmesh
Antiulcer potency of structurally defined low molecular weight modified pectin from turmeric (MTrPP) including inhibitory effects on H. pylori has been demonstrated previously by us. Given that ulcer is a disorder characterized by inflammatory responses leading to initiation, aggravation and perpetuation of disease conditions, the present study aims to understand the possible anti-inflammatory mechanisms through which MTrPP delivered antiulcer effects. Rats triggered with early phase gastric inflammation (LPS) followed by ulcer induction (swim-stress) were pretreated with MTrPP (150 mg/kg b...
June 17, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29924958/overexpression-of-mir-361-5p-in-triple-negative-breast-cancer-tnbc-inhibits-migration-and-invasion-by-targeting-rqcd1-and-inhibiting-the-egfr-pi3k-akt-pathway
#4
Jianjun Han, Jingjing Yu, Yuna Dai, Jumei Li, Meiyan Guo, Jingzhen Song, Xuefeng Zhou
Triple-negative breast cancer (TNBC) is the leading cause of cancer-related death in women. Previous studies indicated that miR-361-5p was downregulated in breast cancer, however, the exact effect of miR-361-5p on TNBC requires further investigation. In the present study, we investigated whether miR-361-5p can act as a tumor suppressor by targeting required for cell differentiation 1 homolog (RQCD1) and inhibiting epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway in TNBC...
June 20, 2018: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29924867/arq-197-a-small-molecule-inhibitor-of-c-met-reduces-tumour-burden-and-prevents-myeloma-induced-bone-disease-in-vivo
#5
Darren L Lath, Clive H Buckle, Holly R Evans, Matthew Fisher, Jenny M Down, Michelle A Lawson, Andrew D Chantry
The receptor tyrosine kinase c-Met, its ligand HGF, and components of the downstream signalling pathway, have all been implicated in the pathogenesis of myeloma, both as modulators of plasma cell proliferation and as agents driving osteoclast differentiation and osteoblast inhibition thus, all these contribute substantially to the bone destruction typically caused by myeloma. Patients with elevated levels of HGF have a poor prognosis, therefore, targeting these entities in such patients may be of substantial benefit...
2018: PloS One
https://www.readbyqxmd.com/read/29924862/identification-of-hepatic-protein-protein-interaction-targets-for-betaine-homocysteine-s-methyltransferase
#6
Francisco Garrido, María Pacheco, Rocío Vargas-Martínez, Roberto Velasco-García, Inmaculada Jorge, Horacio Serrano, Francisco Portillo, Jesús Vázquez, María Ángeles Pajares
Protein-protein interactions are an important mechanism for the regulation of enzyme function allowing metabolite channeling, crosstalk between pathways or the introduction of post-translational modifications. Therefore, a number of high-throughput studies have been carried out to shed light on the protein networks established under different pathophysiological settings. Surprisingly, this type of information is quite limited for enzymes of intermediary metabolism such as betaine homocysteine S-methyltransferase, despite its high hepatic abundancy and its role in homocysteine metabolism...
2018: PloS One
https://www.readbyqxmd.com/read/29924817/a-component-of-the-tor-target-of-rapamycin-nutrient-sensing-pathway-plays-a-role-in-circadian-rhythmicity-in-neurospora-crassa
#7
Lalanthi Ratnayake, Keyur K Adhvaryu, Elizabeth Kafes, Kamyar Motavaze, Patricia Lakin-Thomas
The TOR (Target of Rapamycin) pathway is a highly-conserved signaling pathway in eukaryotes that regulates cellular growth and stress responses. The cellular response to amino acids or carbon sources such as glucose requires anchoring of the TOR kinase complex to the lysosomal/vacuolar membrane by the Ragulator (mammals) or EGO (yeast) protein complex. Here we report a connection between the TOR pathway and circadian (daily) rhythmicity. The molecular mechanism of circadian rhythmicity in all eukaryotes has long been thought to be transcription/translation feedback loops (TTFLs)...
June 20, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29924765/increased-expression-of-p16-in-both-oral-and-genital-lichen-planus
#8
K Danielsson, J Olah, R Zohori-Zangeneh, E Nylander, M Ebrahimi
BACKGROUND: Lichen Planus, LP, is an inflammatory disease of possible autoimmune origin affecting mainly oral and genital mucosa and skin. According to the WHO oral LP is considered a potentially malignant disorders. The p16 tumour suppressor protein can act as an inhibitor of cyclin dependent kinases 4 and 6 and thus down regulate cell cycle progression. Since the discovery of p16 several studies have evaluated its expression in various forms of human cancers. The aim of this study was to evaluate and compare the expression of p16 in oral and genital LP and corresponding healthy mucosa...
June 20, 2018: Medicina Oral, Patología Oral y Cirugía Bucal
https://www.readbyqxmd.com/read/29924731/il-37-affects-the-occurrence-and-development-of-endometriosis-by-regulating-the-biological-behavior-of-endometrial-stromal-cells-through-multiple-signaling-pathways
#9
Jianfa Jiang, Kenan Yu, Zhaoying Jiang, Min Xue
Endometriosis (EMs) is a chronic inflammatory condition. Interleukin (IL)-37 is a member of the IL-1 family and an anti-inflammatory cytokine. This study aimed to evaluate the possible role of IL-37 in the EMs pathogenesis. We investigated the in vivo effect of IL-37 on EMs by injection with recombinant human IL-37 (rhIL-37) into EMs mice. Furthermore, we evaluated the in-vitro effects of IL-37 on proliferation, adhesion, migration, and invasiveness of endometrial stromal cells (ESCs), and explored whether Wnt/β-catenin and mitogen-activated protein kinase (MAPK) pathways were involved in this process...
June 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29924655/genetic-mutations-and-demographic-clinical-and-morphological-aspects-of-myofibrillar-myopathy-in-a-french-cohort
#10
Alzira Alves de Siqueira Carvalho, Emmanuele Lacene, Guy Brochier, Clémance Labasse, Angeline Madelaine, Vinicius Gomes da Silva, Roseli Corazzini, Konstantinos Papadopoulos, Anthony Behin, Pascal Laforêt, Tania Stojkovic, Bruno Eymard, Michel Fardeau, Norma Romero
BACKGROUND: Protein aggregate myopathies (PAM) represent a group of familial or sporadic neuromuscular conditions with marked clinical and genetic heterogeneity that occur in children and adults. Familial PAM includes myofibrillar myopathies defined by the presence of desmin-positive protein aggregates and degenerative intermyofibrillar network changes. PAM is often caused by dysfunctional genes, such as DES, PLEC 1, CRYAB, FLNC, MYOT, ZASP, BAG3, FHL1, and DNAJB6. OBJECTIVE: To retrospectively analyze genetic mutations and demographic, clinical, and morphological aspects of PAM in a French population...
June 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29924419/induction-of-endoplasmic-reticulum-stress-under-endotoxin-tolerance-increases-inflammatory-responses-and-decreases-pseudomonas-aeruginosa-pneumonia
#11
Sena Kim, Yeonsoo Joe, Se-Ung Park, Sun Oh Jeong, Jin-Kyung Kim, Seong Hoon Park, Hyun-Ock Pae, Young-Joon Surh, Jaekyoon Shin, Hun Taeg Chung
Endotoxin tolerance develops in the late phase of sepsis to protect cells from an early hyperinflammatory response. Nonetheless, because it induces an immunosuppressive environment, patients with sepsis in its late phase are affected by secondary infections, particularly bacterial pneumonia. Here, we showed that induction of endoplasmic reticulum (ER) stress leads to activation of glycogen synthase kinase 3β (GSK-3β) and X-box-binding protein 1 (XBP-1) in an inositol-requiring enzyme 1α (IRE1α)-mediated manner, which in turn restores the inflammatory response in endotoxin-tolerant macrophages...
June 20, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29924299/the-rasopathy-family-consequences-of-germline-activation-of-the-ras-mapk-pathway
#12
Mylène Tajan, Romain Paccoud, Sophie Branka, Thomas Edouard, Armelle Yart
Noonan syndrome (NS; Mendelian Inheritance in Men (MIM) ♯163950) and related syndromes (Noonan syndrome with multiple lentigines (NS-ML, formerly called LEOPARD syndrome; MIM ♯151100), Noonan-like syndrome with loose anagen hair (NS-LAH; MIM ♯607721), Costello syndrome (CS; MIM ♯218040), Cardio-Facio-Cutaneous syndrome (CFCS; MIM ♯115150), type I Neurofibromatosis (NF1; MIM ♯162200), and Legius syndrome (LS; MIM ♯611431)) are a group of related genetic disorders, associating distinctive facial features, cardiopathies, growth and skeletal abnormalities, developmental delay/mental retardation, and tumor predisposition...
June 18, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29924131/synthesis-and-molecular-modelling-studies-of-pyrimidinones-and-pyrrolo-3-4-d-pyrimidinodiones-as-new-antiplasmodial-compounds
#13
Kamilla Rodrigues Rogerio, Leonardo J M Carvalho, Luiza Helena Pinto Domingues, Bruno Junior Neves, José Teófilo Moreira Filho, Rosane Nora Castro, Cesare Bianco Júnior, Claudio Tadeu Daniel-Ribeiro, Carolina Horta Andrade, Cedric Stephan Graebin
BACKGROUND Malaria is responsible for 429,000 deaths per year worldwide, and more than 200 million cases were reported in 2015. Increasing parasite resistance has imposed restrictions to the currently available antimalarial drugs. Thus, the search for new, effective and safe antimalarial drugs is crucial. Heterocyclic compounds, such as dihydropyrimidinones (DHPM), synthesised via the Biginelli multicomponent reaction, as well as bicyclic compounds synthesised from DHPMs, have emerged as potential antimalarial candidates in the last few years...
2018: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/29923766/wnk-spak-osr1-signaling-lessons-learned-from-an-insect-renal-epithelium
#14
Aylin R Rodan
WNK (With No Lysine (K)) kinases regulate renal epithelial ion transport to maintain homeostasis of electrolyte concentrations, extracellular volume and blood pressure. The SLC12 cation-chloride cotransporters, including the sodium-potassium-2-chloride (NKCC) and sodium-chloride (NCC) cotransporters, are targets of WNK regulation via the intermediary kinases SPAK (Ste20-related proline/alanine-rich kinase) and OSR1 (oxidative stress response). The pathway is activated by low dietary potassium intake, resulting in increased phosphorylation and activity of NCC...
June 20, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29923654/the-tri-snrnp-specific-protein-fgsnu66-is-functionally-related-to-fgprp4-kinase-in-fusarium-graminearum
#15
Manli Sun, Yimei Zhang, Qinhu Wang, Chunlan Wu, Cong Jiang, Jin-Rong Xu
Deletion of Prp4, the only kinase among spliceosome components, is not lethal in Fusarium graminearum but Fgprp4 mutants have severe growth defects and produced spontaneous suppressors. To identify novel suppressor mutations of Fgprp4, we sequenced the genome of suppressor S37 that was normal in growth but only partially recovered for intron splicing and identified a tandem duplication of 9-aa in the tri-snRNP component FgSNU66. Among the 19 additional suppressor strains found to have mutations in FgSNU66 (out of 260 screened), five had the same 9-aa duplication event with S37 and another five had the R477H/C mutation...
June 20, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29923635/two-cases-of-dabrafenib-and-trametinib-therapy-failed-advanced-melanoma-successfully-controlled-by-nivolumab-monotherapy
#16
Yota Sato, Taku Fujimura, Yumi Kambayashi, Kayo Tanita, Hisayuki Tono, Akira Hashimoto, Setsuya Aiba
Although therapies for advanced melanoma have been greatly improved by the development of immune checkpoint inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors, there are still many concerns about the administration of these novel drugs. Therefore, to combine these therapies sequentially at appropriate time points of the disease is important. In this report, we report two cases in which dabrafenib and trametinib therapy for advanced melanoma failed but were successfully controlled by nivolumab monotherapy, and investigated the sera sCD163, CCL22 and CXCL10 as biomarkers for tumor progression...
June 20, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29923456/transcription-independent-expression-of-pkm%C3%AE-in-the-anterior-cingulate-cortex-contributes-to-chronically-maintained-neuropathic-pain
#17
Hyoung-Gon Ko, Sanghyun Ye, Dae-Hee Han, Pojeong Park, Chae-Seok Lim, Kyungmin Lee, Min Zhuo, Bong-Kiun Kaang
Protein kinase M ζ is well known for its role in maintaining memory and pain. Previously, we revealed that the activation of protein kinase M ζ in the anterior cingulate cortex plays a role in sustaining neuropathic pain. However, the mechanism by which protein kinase M ζ is expressed in the anterior cingulate cortex by peripheral nerve injury, and whether blocking of protein kinase M ζ using its inhibitor, zeta inhibitory peptide, produces analgesic effects in neuropathic pain maintained chronically after injury, have not previously been resolved...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29923200/egfl7-master-regulator-of-cancer-pathogenesis-angiogenesis-and-an-emerging-mediator-of-bone-homeostasis
#18
REVIEW
Guoju Hong, Vincent Kuek, Jiaxi Shi, Lin Zhou, Xiaorui Han, Wei He, Jennifer Tickner, Heng Qiu, Qiushi Wei, Jiake Xu
Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion...
June 19, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29923153/black-tea-affects-obesity-by-reducing-nutrient-intake-and-activating-amp-activated-protein-kinase-in-mice
#19
Shunshun Pan, Xuming Deng, Shili Sun, Xingfei Lai, Lingli Sun, Qiuhua Li, Limin Xiang, Lingzhi Zhang, Yahui Huang
The effects of certain tea components on the prevention of obesity in humans have been reported recently. However, whether Yinghong NO. 9 black tea consumption has beneficial effects on obesity are not known. Here, we obtained a Yinghong NO. 9 black tea infusion (Y9 BTI) and examined the anti-obesity effects of its oral administration. ICR mice were fed a standard diet supplemented with Y9 BTI at 0.5, 1.0, or 2.0 g/kg body weight for two weeks, and the body weight were recorded. HE staining was used to evaluate the effect of Y9 BTI on mice liver...
June 19, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29923116/cardiospecific-deletion-of-%C3%AE-e-catenin-leads-to-heart-failure-and-lethality-in-mice
#20
Volodymyr V Balatskyi, Larysa L Macewicz, Ana-Maria Gan, Sergii V Goncharov, Paulina Pawelec, Georgiy V Portnichenko, Tetiana Yu Lapikova-Bryginska, Viktor O Navrulin, Victor E Dosenko, Adam Olichwier, Pawel Dobrzyn, Oksana O Piven
αE-catenin is a component of adherens junctions that link the cadherin-catenin complex to the actin cytoskeleton. The signaling function of this protein was recently revealed. In the present study, we investigated the role of αE-catenin in the pathogenesis of heart failure. We mated αE-catenin conditional knockout mice with αMHC-Cre mice and evaluated their mutant offspring. We found that αE-catenin knockout caused enlargement of the heart and atria, fibrosis, the upregulation of hypertrophic genes, and the dysregulation of fatty acid metabolism via the transcriptional activity of Yap and β-catenin...
June 20, 2018: Pflügers Archiv: European Journal of Physiology
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