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https://www.readbyqxmd.com/read/28727830/the-receptor-tyrosine-kinase-axl-promotes-migration-and-invasion-in-colorectal-cancer
#1
Diana J Uribe, Edward K Mandell, Adam Watson, Jesse D Martinez, Jonathan A Leighton, Sourav Ghosh, Carla V Rothlin
The receptor tyrosine kinases (RTKs) TYRO3, AXL and MERTK (TAM) have well-described oncogenic functions in a number of cancers. Notwithstanding, TAM RTKs are also potent and indispensable inhibitors of inflammation. The combined deletion of Axl and Mertk in mice enhances chronic inflammation and autoimmunity, including increased inflammation in the gut and colitis-associated cancer. On the other hand, deletion of Tyro3 increases the risk of allergic responses. Therefore, the indiscriminate inhibition of these TAM RTKs could result in undesirable immunological diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28710321/correction-unc2025-a-mertk-small-molecule-inhibitor-is-therapeutically-effective-alone-and-in-combination-with-methotrexate-in-leukemia-models
#2
(no author information available yet)
No abstract text is available yet for this article.
July 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28626217/irf8-regulates-the-progression-of-myeloproliferative-neoplasm-mpn-like-syndrome-via-mertk-signaling-in-zebrafish
#3
F Zhao, Y Shi, Y Huang, Y Zhan, L Zhou, Y Li, Y Wan, H Li, H Huang, H Ruan, L Luo, L Li
Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8 mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28621419/tam-receptor-signaling-in-development
#4
Tal Burstyn-Cohen
TYRO3, AXL and MERTK comprise the TAM family of receptor protein tyrosine kinases. Activated by their ligands, protein S (PROS1) and growth-arrest-specific 6 (GAS6), they mediate numerous cellular functions throughout development and adulthood. Expressed by a myriad of cell types and tissues, they have been implicated in homeostatic regulation of the immune, nervous, vascular, bone and reproductive systems. The loss-of-function of TAM signaling in adult tissues culminates in the destruction of tissue homeostasis and diseased states, while TAM gain-of-function in various tumors promotes cancer phenotypes...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28605477/mertk-as-a-therapeutic-target-in-glioblastoma
#5
Jing Wu, Lauren N Frady, Ryan E Bash, Stephanie M Cohen, Allison N Schorzman, Yu-Ting Su, David M Irvin, William C Zamboni, Xiaodong Wang, Stephen V Frye, Matthew G Ewend, Erik P Sulman, Mark R Gilbert, H Shelton Earp, C Ryan Miller
Background: Glioma-associated macrophages and microglia (GAMs) are components of the glioblastoma (GBM) microenvironment that express MerTK, a receptor tyrosine kinase that triggers efferocytosis and can suppress innate immune responses. The aim of the study was to define MerTK as a therapeutic target using an orally bioavailable inhibitor, UNC2025. Methods: We examined MerTK expression in tumor cells and macrophages in matched patient GBM samples by double-label immunohistochemistry...
June 12, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28601603/enhanced-classical-complement-pathway-activation-and-altered-phagocytosis-signaling-molecules-in-human-epilepsy
#6
Season K Wyatt, Thomas Witt, Nicholas M Barbaro, Aaron A Cohen-Gadol, Amy L Brewster
Microglia-mediated neuroinflammation is widely associated with seizures and epilepsy. Although microglial cells are professional phagocytes, less is known about the status of this phenotype in epilepsy. Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in microglia-mediated synaptic pruning. Interestingly, in human and experimental epilepsy, altered mRNA levels of complement molecules were reported. Therefore, to identify a potential role for complement and microglia in the synaptodendritic pathology of epilepsy, we determined the protein levels of classical complement proteins (C1q-C3) along with other phagocytosis signaling molecules in human epilepsy...
June 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28599271/mtorc1-autophagy-regulated-mertk-in-mutant-brafv600-melanoma-with-acquired-resistance-to-braf-inhibition
#7
Gongda Xue, Reto Kohler, Fengyuan Tang, Debby Hynx, Yuhua Wang, Francesca Orso, Vincent Prêtre, Reto Ritschard, Petra Hirschmann, Peter Cron, Tim Roloff, Reinhard Dummer, Mario Mandalà, Sandrine Bichet, Christel Genoud, Alexandra G Meyer, Manuele G Muraro, Giulio C Spagnoli, Daniela Taverna, Curzio Rüegg, Taha Merghoub, Daniela Massi, Huifang Tang, Mitchell P Levesque, Stephan Dirnhofer, Alfred Zippelius, Brian A Hemmings, Andreas Wicki
BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors (MEKi) were recently approved for therapy of metastatic melanomas harbouring the oncogenic BRAFV600 mutation. Although these therapies have shown pronounced therapeutic efficacy, the limited durability of the response indicates an acquired drug resistance that still remains mechanistically poorly understood at the molecular level. We conducted transcriptome gene profiling in BRAFi-treated melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically upregulated...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28539349/sleep-loss-promotes-astrocytic-phagocytosis-and-microglial-activation-in-mouse-cerebral-cortex
#8
Michele Bellesi, Luisa de Vivo, Mattia Chini, Francesca Gilli, Giulio Tononi, Chiara Cirelli
We previously found that Mertk and its ligand Gas6, astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested that astrocytes may engage in phagocytic activity during extended wake, but direct evidence was lacking. Studies in humans and rodents also found that sleep loss increases peripheral markers of inflammation, but whether these changes are associated with neuroinflammation and/or activation of microglia, the brain's resident innate immune cells, was unknown...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28528507/mertk-does-not-mediate-phagocytosis-of-staphylococcus-aureus-but-attenuates-inflammation-induced-by-staphylococcal-lipoteichoic-acid-through-blocking-nf-%C3%AE%C2%BAb-activation
#9
Bing Zhang, Huimei Wu, Lei Fang, Peishan Ding, Ke Xu, Qingbin Yang, Rongyu Liu
Mer receptor tyrosine kinase (MerTK) expressed in macrophages is essential for phagocytosis of apoptotic cells. Here, we investigate whether MerTK is involved in the phagocytosis of Staphylococcus aureus (S. aureus) and regulation of staphylococcal lipoteichoic acid (LTA)-induced inflammatory response in macrophages. We found that stimulating RAW264.7 macrophages with S. aureus activated multiple signaling pathways including toll-like receptor 2 (TLR2), scavenger receptor A (SR-A), and MerTK. Meanwhile, S. aureus stimulation also induced activation of proteins focal adhesion kinase (FAK) and Rac1, which are related to phagocytosis...
May 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28500071/activated-microglia-desialylate-and-phagocytose-cells-via-neuraminidase-galectin-3-and-mer-tyrosine-kinase
#10
Koji Nomura, Anna Vilalta, David H Allendorf, Tamara C Hornik, Guy C Brown
Activated microglia can phagocytose dying, stressed, or excess neurons and synapses via the phagocytic receptor Mer tyrosine kinase (MerTK). Galectin-3 (Gal-3) can cross-link surface glycoproteins by binding galactose residues that are normally hidden below terminal sialic acid residues. Gal-3 was recently reported to opsonize cells via activating MerTK. We found that LPS-activated BV-2 microglia rapidly released Gal-3, which was blocked by calcineurin inhibitors. Gal-3 bound to MerTK on microglia and to stressed PC12 (neuron-like) cells, and it increased microglial phagocytosis of PC12 cells or primary neurons, which was blocked by inhibition of MerTK...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28476232/genetics-of-pheochromocytomas-and-paragangliomas-an-overview-on-the-recently-implicated-genes-mertk-met-fibroblast-growth-factor-receptor-1-and-h3f3a
#11
REVIEW
Rodrigo Almeida Toledo
Genomic studies conducted by different centers have uncovered various new genes mutated in pheochromocytomas and paragangliomas (PPGLs) at germline, mosaic, and/or somatic levels, greatly expanding our knowledge of the genetic events occurring in these tumors. The current review focuses on very new findings and discusses the previously not recognized role of MERTK, MET, fibroblast growth factor receptor 1, and H3F3A genes in syndromic and nonsyndromic PPGLs. These 4 new genes were selected because although their association with PPGLs is very recent, mounting evidence was generated that rapidly consolidated the prominence of these genes in the molecular pathogenesis of PPGLs...
June 2017: Endocrinology and Metabolism Clinics of North America
https://www.readbyqxmd.com/read/28473436/dba-2j-haplotype-on-distal-chromosome-2-reduces-mertk-expression-restricts-efferocytosis-and-increases-susceptibility-to-atherosclerosis
#12
COMPARATIVE STUDY
Yukako Kayashima, Natalia Makhanova, Nobuyo Maeda
OBJECTIVE: Arch atherosclerosis 4 (Aath4) is a quantitative trait locus for atherosclerotic plaque formation in the inner curve of the aortic arch previously identified in an F2 cross of Apoe(-/-) mice on DBA/2J and 129S6 backgrounds. C-mer proto-oncogene tyrosine kinase (Mertk), coding for a ligand-activated transmembrane tyrosine kinase, is a candidate gene within the same chromosomal region. Our objective was to determine whether strain differences in Mertk influence plaque formation...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28462455/a-novel-mertk-mutation-causing-retinitis-pigmentosa
#13
Hasenin Al-Khersan, Kaanan P Shah, Segun C Jung, Alex Rodriguez, Ravi K Madduri, Michael A Grassi
PURPOSE: Retinitis pigmentosa (RP) is a genetically heterogeneous inherited retinal dystrophy. To date, over 80 genes have been implicated in RP. However, the disease demonstrates significant locus and allelic heterogeneity not entirely captured by current testing platforms. The purpose of the present study was to characterize the underlying mutation in a patient with RP without a molecular diagnosis after initial genetic testing. METHODS: Whole-exome sequencing of the affected proband was performed...
May 1, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28450389/mertk-expressing-hepatic-macrophages-promote-the-resolution-of-inflammation-in-acute-liver-failure
#14
Evangelos Triantafyllou, Oltin T Pop, Lucia A Possamai, Annika Wilhelm, Evaggelia Liaskou, Arjuna Singanayagam, Christine Bernsmeier, Wafa Khamri, Gemma Petts, Rebecca Dargue, Scott P Davies, Joseph Tickle, Muhammed Yuksel, Vishal C Patel, Robin D Abeles, Zania Stamataki, Stuart M Curbishley, Yun Ma, Ian D Wilson, Muireann Coen, Kevin J Woollard, Alberto Quaglia, Julia Wendon, Mark R Thursz, David H Adams, Chris J Weston, Charalambos G Antoniades
OBJECTIVE: Acute liver failure (ALF) is characterised by overwhelming hepatocyte death and liver inflammation with massive infiltration of myeloid cells in necrotic areas. The mechanisms underlying resolution of acute hepatic inflammation are largely unknown. Here, we aimed to investigate the impact of Mer tyrosine kinase (MerTK) during ALF and also examine how the microenvironmental mediator, secretory leucocyte protease inhibitor (SLPI), governs this response. DESIGN: Flow cytometry, immunohistochemistry, confocal imaging and gene expression analyses determined the phenotype, functional/transcriptomic profile and tissue topography of MerTK+ monocytes/macrophages in ALF, healthy and disease controls...
April 27, 2017: Gut
https://www.readbyqxmd.com/read/28423319/tam-receptors-are-not-required-for-zika-virus-infection-in-mice
#15
Andrew K Hastings, Laura J Yockey, Brett W Jagger, Jesse Hwang, Ryuta Uraki, Hallie F Gaitsch, Lindsay A Parnell, Bin Cao, Indira U Mysorekar, Carla V Rothlin, Erol Fikrig, Michael S Diamond, Akiko Iwasaki
Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl(-/-), Mertk(-/-), Axl(-/-)Mertk(-/-), and Axl(-/-)Tyro3(-/-) mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28398482/cerkl-gene-knockout-disturbs-photoreceptor-outer-segment-phagocytosis-and-causes-rod-cone-dystrophy-in-zebrafish
#16
Shanshan Yu, Chang Li, Lincoln Biswas, Xuebin Hu, Fei Liu, James Reilly, Xiliang Liu, Ying Liu, Yuwen Huang, Zhaojing Lu, Shanshan Han, Lei Wang, Jing Yu Liu, Tao Jiang, Xinhua Shu, Fulton Wong, Zhaohui Tang, Mugen Liu
In humans, CERKL mutations cause widespread retinal degeneration: early dysfunction and loss of rod and cone photoreceptors in the outer retina and, progressively, death of cells in the inner retina. Despite intensive efforts, the function of CERKL remains obscure and studies in animal models have failed to clarify the disease mechanism of CERKL mutations. To address this gap in knowledge, we have generated a stable CERKL knockout zebrafish model by TALEN technology and a 7bp deletion in CERKL cDNA that caused the premature termination of CERKL...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28398481/mertk-rs4374383-variant-predicts-incident-nonalcoholic-fatty-liver-disease-and-diabetes-role-of-mononuclear-cell-activation-and-adipokine-response-to-dietary-fat
#17
Giovanni Musso, Maurizio Cassader, Franco De Michieli, Elena Paschetta, Silvia Pinach, Francesca Saba, Daria Bongiovanni, Luciana Framarin, Mara Berrutti, Nicola Leone, Stefania Corvisieri, Renato Parente, Federica Molinaro, Antonio Sircana, Simona Bo, Roberto Gambino
No abstract text is available yet for this article.
May 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28369510/antagonistic-coevolution-of-mer-tyrosine-kinase-expression-and-function
#18
Amanda L Evans, Jack W D Blackburn, Kyle Taruc, Angela Kipp, Brennan S Dirk, Nina R Hunt, Stephen D Barr, Jimmy D Dikeakos, Bryan Heit
TYRO3, AXL, and MERTK (TAM) receptors are a family of receptor tyrosine kinases that maintain homeostasis through the clearance of apoptotic cells, and when defective, contribute to chronic inflammatory and autoimmune diseases such as atherosclerosis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and Crohn's disease. In addition, certain enveloped viruses utilize TAM receptors for immune evasion and entry into host cells, with several viruses preferentially hijacking MERTK for these purposes...
July 1, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28338112/pnpla3-and-rnf7-gene-variants-are-associated-with-the-risk-of-developing-liver-fibrosis-and-cirrhosis-in-an-eastern-european-population
#19
Juozas Kupcinskas, Irena Valantiene, Greta Varkalaitė, Ruta Steponaitiene, Jurgita Skieceviciene, Jolanta Sumskiene, Vitalija Petrenkiene, Jurate Kondrackiene, Gediminas Kiudelis, Frank Lammert, Limas Kupcinskas
BACKGROUND AND AIMS: Genome-wide association studies have revealed an association between the risk of developing liver fibrosis or cirrhosis and the single nucleotide polymorphisms (SNPs) of the PNPLA3, RNF7, MERTK and PCSK7 genes. We aimed to validate these results in an Eastern European population. METHODS: We evaluated the associations between the PNPLA3 (rs738409), RNF7 (rs16851720), MERTK (rs4374383) and PCSK7 (rs236918) variants and liver fibrosis and cirrhosis in a series of consecutive patients recruited at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital, during the period 2012-2015...
March 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28334911/mertk-rs4374383-variant-predicts-incident-nonalcoholic-fatty-liver-disease-and-diabetes-role-of-mononuclear-cell-activation-and-adipokine-response-to-dietary-fat
#20
Giovanni Musso, Maurizio Cassader, Franco De Michieli, Elena Paschetta, Silvia Pinach, Francesca Saba, Daria Bongiovanni, Luciana Framarin, Mara Berrutti, Nicola Leone, Stefania Corvisieri, Renato Parente, Federica Molinaro, Antonio Sircana, Simona Bo, Roberto Gambino
The loss-of-function rs4374383 G > A variant in Myeloid-epithelial-reproductive Tyrosine Kinase (MERTK) gene has been linked to hepatic fibrosis in chronic liver diseases. MERTK is expressed by immune and non-immune cells involved in inflammation, metabolism and vascular homeostasis. We assessed the impact of MERTK rs4374383 G > A variant on nonalcoholic fatty liver disease (NAFLD) incidence and severity and on glucose and lipid metabolism. We followed-up 305 healthy nonobese nondiabetic, metabolic syndrome-free insulin sensitive participants in a population-based study, characterized for MERTK G > A polymorphism, adipokine profile and inflammatory markers...
May 1, 2017: Human Molecular Genetics
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