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https://www.readbyqxmd.com/read/28346224/mutant-%C3%AE-2-chimaerin-signals-via-bidirectional-ephrin-pathways-in-duane-retraction-syndrome
#1
Alicia A Nugent, Jong G Park, Yan Wei, Alan P Tenney, Nicole M Gilette, Michelle M DeLisle, Wai-Man Chan, Long Cheng, Elizabeth C Engle
Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1KI/KI) that models DRS. Whole embryo imaging of Chn1KI/KI mice revealed stalled abducens nerve growth and selective trochlear and first cervical spinal nerve guidance abnormalities. Stalled abducens nerve bundles did not reach the orbit, resulting in secondary aberrant misinnervation of the lateral rectus muscle by the oculomotor nerve...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28341121/activation-of-epha1-epha-receptor-axis-attenuates-diabetic-nephropathy-in-mice
#2
Yihui Li, Hongdan Yan, Feng Wang, Shanying Huang, Yun Zhang, Zhihao Wang, Ming Zhong, Wei Zhang
The Eph family of receptor tyrosine kinases serves as key modulators of various cellular functions, including inflammation, hypertrophy and fibrosis. Recent analyses have revealed that a member of the Eph family, EphA1, plays a pivotal role in regulating insulin metabolism and kidney injury. However, the importance of EphA1 in diabetic nephropathy has not been recognized. We established a diabetic nephropathy mouse model using a high-fat diet and streptozotocin (STZ) injection. Then, the recombinant adeno-associated virus type 9 (AAV9) overexpressing EphA1 or a negative control was injected locally into the kidney...
March 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28338017/a-role-of-the-sam-domain-in-epha2-receptor-activation
#3
Xiaojun Shi, Vera Hapiak, Ji Zheng, Jeannine Muller-Greven, Deanna Bowman, Ryan Lingerak, Matthias Buck, Bing-Cheng Wang, Adam W Smith
Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322822/asymmetry-at-cell-cell-interfaces-direct-cell-sorting-boundary-formation-and-tissue-morphogenesis
#4
REVIEW
Rosa Ventrella, Nihal Kaplan, Spiro Getsios
During development, cells of seemingly homogenous character sort themselves out into distinct compartments in order to generate cell types with specialized features that support tissue morphogenesis and function. This process is often driven by receptors at the cell membrane that probe the extracellular microenvironment for specific ligands and alter downstream signaling pathways impacting transcription, cytoskeletal organization, and cell adhesion to regulate cell sorting and subsequent boundary formation...
March 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28294115/phosphorylation-of-rab-coupling-protein-by-lmtk3-controls-rab14-dependent-epha2-trafficking-to-promote-cell-cell-repulsion
#5
Christine Gundry, Sergi Marco, Elena Rainero, Bryan Miller, Emmanuel Dornier, Louise Mitchell, Patrick T Caswell, Andrew D Campbell, Anna Hogeweg, Owen J Sansom, Jennifer P Morton, Jim C Norman
The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28276447/ascl1-promotes-tangential-migration-and-confines-migratory-routes-by-induction-of-ephb2-in-the-telencephalon
#6
Yuan-Hsuan Liu, Jin-Wu Tsai, Jia-Long Chen, Wan-Shan Yang, Pei-Ching Chang, Pei-Lin Cheng, David L Turner, Yuchio Yanagawa, Tsu-Wei Wang, Jenn-Yah Yu
During development, cortical interneurons generated from the ventral telencephalon migrate tangentially into the dorsal telencephalon. Although Achaete-scute family bHLH transcription factor 1 (Ascl1) plays important roles in the developing telencephalon, whether Ascl1 regulates tangential migration remains unclear. Here, we found that Ascl1 promoted tangential migration along the ventricular zone/subventricular zone (VZ/SVZ) and intermediate zone (IZ) of the dorsal telencephalon. Distal-less homeobox 2 (Dlx2) acted downstream of Ascl1 in promoting tangential migration along the VZ/SVZ but not IZ...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28262839/loss-of-the-eph-receptor-b6-contributes-to-colorectal-cancer-metastasis
#7
Silvia Mateo-Lozano, Sarah Bazzocco, Paulo Rodrigues, Rocco Mazzolini, Elena Andretta, Higinio Dopeso, Yolanda Fernández, Edgar Del Llano, Josipa Bilic, Lucía Suárez-López, Irati Macaya, Fernando Cartón-García, Rocio Nieto, Lizbeth M Jimenez-Flores, Priscila Guimarães de Marcondes, Yaiza Nuñez, Elsa Afonso, Karina Cacci, Javier Hernández-Losa, Stefania Landolfi, Ibane Abasolo, Santiago Ramón Y Cajal, John M Mariadason, Simo Schwartz, Toshimitsu Matsui, Diego Arango
Although deregulation of EPHB signaling has been shown to be an important step in colorectal tumorigenesis, the role of EPHB6 in this process has not been investigated. We found here that manipulation of EPHB6 levels in colon cancer cell lines has no effect on their motility and growth on a solid substrate, soft agar or in a xenograft mouse model. We then used an EphB6 knockout mouse model to show that EphB6 inactivation does not efficiently initiate tumorigenesis in the intestinal tract. In addition, when intestinal tumors are initiated genetically or pharmacologically in EphB6(+/+) and EphB6(-/-) mice, no differences were observed in animal survival, tumor multiplicity, size or histology, and proliferation of intestinal epithelial cells or tumor cells...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255696/reconstitution-of-tcr-signaling-using-supported-lipid-bilayers
#8
Xiaolei Su, Jonathon A Ditlev, Michael K Rosen, Ronald D Vale
Biochemical reconstitution has served as an important tool for understanding the mechanisms of many cellular processes including DNA replication, transcription, translation, vesicle trafficking, and ubiquitin-mediated proteolysis. Here, we demonstrate that biochemical reconstitution can be applied to studying a complex signaling pathway involving as many as 12 proteins or protein complexes acting at the surface of model membranes. We show that a temporal sequence of events in activated T cells beginning with phosphorylation of the T cell receptor and culminating in the activation of actin polymerization can be replicated in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28214829/ephb4-regulates-self-renewal-proliferation-and-neuronal-differentiation-of-human-embryonic-neural-stem-cells-in-vitro
#9
Tingting Liu, Xianwei Zeng, Fangling Sun, Hongli Hou, Yunqian Guan, Deyu Guo, Houxi Ai, Wen Wang, Guojun Zhang
BACKGROUND/AIMS: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. METHODS: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs...
February 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28194092/paradoxes-of-the-ephb1-receptor-in-malignant-brain-tumors
#10
REVIEW
Wenqiang Wei, Hongju Wang, Shaoping Ji
Eph receptors are a subfamily of receptor tyrosine kinases. Eph receptor-mediated forward and ephrin ligand-mediated reverse signalings are termed bidirectional signaling. Increasing evidence shows that Eph/ephrin signaling regulates cell migration, adhesion, morphological changes, differentiation, proliferation and survival through cell-cell communication. Some recent studies have started to implicate Eph/ephrin signaling in tumorigenesis, metastasis, and angiogenesis. Previous studies have shown that EphB1 receptor and its ephrin ligands are expressed in the central nervous system...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28171762/ephs-and-ephrins
#11
Hannah Taylor, Jessica Campbell, Catherine D Nobes
Eph receptors comprise the largest family of receptor tyrosine kinases (RTKs), with fourteen receptors divided into two subfamilies - EphAs and EphBs. Yet, despite their multitude of functions in almost all tissues of the body, these receptors represent one of the most underappreciated RTK families. What makes Eph receptors unique is that their cognate ligands, the ephrins, are tethered to the cell surface, in contrast to other RTKs whose ligands are generally soluble. This phenomenon means that signalling through Eph receptors is largely dependent on cell-cell contact...
February 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28169277/investigation-of-the-role-of-tyrosine-kinase-receptor-epha3-in-colorectal-cancer
#12
Elena Andretta, Fernando Cartón-García, Águeda Martínez-Barriocanal, Priscila Guimarães de Marcondes, Lizbeth M Jimenez-Flores, Irati Macaya, Sarah Bazzocco, Josipa Bilic, Paulo Rodrigues, Rocio Nieto, Stefania Landolfi, Santiago Ramon Y Cajal, Simo Schwartz, Arthur Brown, Higinio Dopeso, Diego Arango
EPH signaling deregulation has been shown to be important for colorectal carcinogenesis and genome-wide sequencing efforts have identified EPHA3 as one of the most frequently mutated genes in these tumors. However, the role of EPHA3 in colorectal cancer has not been thoroughly investigated. We show here that ectopic expression of wild type EPHA3 in colon cancer cells did not affect their growth, motility/invasion or metastatic potential in vivo. Moreover, overexpression of mutant EPHA3 or deletion of the endogenous mutant EPHA3 in colon cancer cells did not affect their growth or motility...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28165374/evaluation-of-epha2-and-ephb4-as-targets-for-image-guided-colorectal-cancer-surgery
#13
Marieke A Stammes, Hendrica A J M Prevoo, Meyke C Ter Horst, Stéphanie A Groot, Cornelis J H Van de Velde, Alan B Chan, Lioe-Fee de Geus-Oei, Peter J K Kuppen, Alexander L Vahrmeijer, Elena B Pasquale, Cornelis F M Sier
Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH...
February 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28145630/specific-photothermal-ablation-therapy-of-endometriosis-by-targeting-delivery-of-gold-nanospheres
#14
Xiaomeng Guo, Wei Li, Jialin Zhou, Wanqing Hou, Xue Wen, Hanbo Zhang, Fenfen Kong, Lihua Luo, Qingpo Li, Yongzhong Du, Jian You
Endometriosis is difficult to treat since the side effects of the current therapeutic method and the high recurrence rate; thus, newer and safer therapeutic approaches are urgently needed. This work investigates the enhanced permeability and retention effect of CdTe quantum dots (QDs) and hollow gold nanospheres (HAuNS) in endometriosis to increase the delivery of HAuNS into lesion cells. The surface of HAuNS is successfully conjugated with a TNYL peptide that has specific affinity for the EphB4 receptor, which is a member of the Eph family of receptor tyrosine kinases...
February 1, 2017: Small
https://www.readbyqxmd.com/read/28143955/the-eph-related-tyrosine-kinase-ligand-ephrin-b1-marks-germinal-center-and-memory-precursor-b-cells
#15
Brian J Laidlaw, Timothy H Schmidt, Jesse A Green, Christopher D C Allen, Takaharu Okada, Jason G Cyster
Identification of germinal center (GC) B cells is typically reliant on the use of surface activation markers that exhibit a wide range of expression. Here, we identify Ephrin-B1, a ligand for Eph-related receptor tyrosine kinases, as a specific marker of mature GC B cells. The number of Ephrin-B1(+) GC B cells increases during the course of an immune response with Ephrin-B1(+) GC B cells displaying elevated levels of Bcl6, S1pr2, and Aicda relative to their Ephrin-B1(-) counterparts. We further identified a small proportion of recently dividing, somatically mutated Ephrin-B1(+) GC B cells that have begun to down-regulate Bcl6 and S1pr2 and express markers associated with memory B cells, such as CD38 and EBI2...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28140668/a-family-with-craniofrontonasal-syndrome-the-first-report-of-familial-cases-of-craniofrontonasal-syndrome-with-bilateral-cleft-lip-and-palate
#16
Yoshikazu Inoue, Yoshiaki Sakamoto, Masanori Sugimoto, Hidehito Inagaki, Hiroko Boda, Masafumi Miyata, Hideteru Kato, Hiroki Kurahashi, Takayuki Okumoto
Craniofrontonasalsyndrome (CFNS) is a very rare genetic disorder, the common physical malformations of which include coronal synostosis, widely spaced eyes, clefting of the nasal tip, and various skeletal anomalies. Mutations of EFNB1, which encodes a member of the ephrin family of transmembrane ligands for Eph receptor tyrosine kinases, is the cause of CFNS. Although familial CFNS cases have been reported, no studies in the literature describe familial cases of CFNS expressing bilateral cleft lip and palate...
January 31, 2017: Cleft Palate-craniofacial Journal
https://www.readbyqxmd.com/read/28120491/ephb3-protein-is-associated-with-histological-grade-and-figo-stage-in-ovarian-serous-carcinomas
#17
Weiwei Gao, Qin Zhang, Yan Wang, Jiandong Wang, Shu Zhang
Eph (Erythropoietin-producing human hepatocellular carcinoma cell) is the largest subfamily of receptor tyrosine kinases. Eph receptors and their ephrin ligands are involved in embryonic development and physiological processes. Aberrant expression of Eph/ephrin may contribute to a variety of diseases including cancer. EphB3 is a member of Eph receptors and has been found to play roles in carcinogenesis of some types of human cancer. But, its expression and clinical significance in ovarian serous carcinoma have not been well investigated and are unknown...
February 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28108514/somatic-ephrin-receptor-mutations-are-associated-with-metastasis-in-primary-colorectal-cancer
#18
Lucy Mathot, Snehangshu Kundu, Viktor Ljungström, Jessica Svedlund, Lotte Moens, Tom Adlerteg, Elin Falk-Sörqvist, Verónica Rendo, Claudia Bellomo, Markus Mayrhofer, Carme Cortina, Magnus Sundström, Patrick Micke, Johan Botling, Anders Isaksson, Aristidis Moustakas, Eduard Batlle, Helgi Birgisson, Bengt Glimelius, Mats Nilsson, Tobias Sjöblom
The contribution of somatic mutations to metastasis of colorectal cancers (CRC) is currently unknown. To find mutations involved in the CRC metastatic process, we performed deep mutational analysis of 676 genes in 107 stages II-IV primary CRC, of which half had metastasized. The mutation prevalence in the ephrin (Eph) family of tyrosine kinase receptors was ten-fold higher in primary tumors of metastatic CRC than in non-metastatic cases and preferentially occurred in stage III and IV tumours. Mutational analyses in situ confirmed expression of mutant Eph receptors...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28096261/tuning-collective-cell-migration-by-cell-cell-junction-regulation
#19
Peter Friedl, Roberto Mayor
Collective cell migration critically depends on cell-cell interactions coupled to a dynamic actin cytoskeleton. Important cell-cell adhesion receptor systems implicated in controlling collective movements include cadherins, immunoglobulin superfamily members (L1CAM, NCAM, ALCAM), Ephrin/Eph receptors, Slit/Robo, connexins and integrins, and an adaptive array of intracellular adapter and signaling proteins. Depending on molecular composition and signaling context, cell-cell junctions adapt their shape and stability, and this gradual junction plasticity enables different types of collective cell movements such as epithelial sheet and cluster migration, branching morphogenesis and sprouting, collective network migration, as well as coordinated individual-cell migration and streaming...
January 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28095646/a-frog-s-view-of-ephrinb-signaling
#20
REVIEW
Yoo-Seok Hwang, Ira O Daar
Cell-cell and cell-substrate adhesion are essential to the proper formation and maintenance of tissue patterns during development, and deregulation of these processes can lead to invasion and metastasis of cancer cells. Cell surface adhesion and signaling molecules are key players in both normal development and cancer progression. One set of cell surface proteins, the Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, are significant regulators of these processes. During embryonic development, the Eph/ephrin signaling system is involved in cell-cell contact events that result in cell sorting and boundary formation between receptor and ligand bearing cells...
January 2017: Genesis: the Journal of Genetics and Development
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