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https://www.readbyqxmd.com/read/27926875/ship2-regulates-lumen-generation-cell-division-and-ciliogenesis-through-the-control-of-basolateral-to-apical-lumen-localization-of-aurora-a-and-hef-1
#1
Ola Hamze-Komaiha, Sokavuth Sarr, Yannick Arlot-Bonnemains, Didier Samuel, Ama Gassama-Diagne
Lumen formation during epithelial morphogenesis requires the creation of a luminal space at cell interfaces named apical membrane-initiation sites (AMISs). This is dependent upon integrated signaling from mechanical and biochemical cues, vesicle trafficking, cell division, and processes tightly coupled to ciliogenesis. Deciphering relationships between polarity determinants and lumen or cilia generation remains a fundamental issue. Here, we report that Src homology 2 domain-containing inositol 5-phosphatase 2 (SHIP2), a basolateral determinant of polarity, regulates RhoA-dependent actin contractility and cell division to form AMISs...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27907247/ship2-structure-function-and-inhibition
#2
Mark P Thomas, Christophe Erneux, Barry V L Potter
SHIP2 is a phosphatase that acts at the 5-position of phosphatidylinositol 3,4,5-trisphosphate. It is one of several enzymes that catalyse dephosphorylation at the 5-position of phosphoinositides or inositol phosphates. SHIP2 has a confirmed role in opsismodysplasia, a disease of bone development, but also interacts with proteins involved in insulin signalling, cytoskeletal function (thus having an impact on endocytosis, adhesion, proliferation and apoptosis) and immune system function. The structure of three domains (constituting about 38% of the protein) is known...
November 30, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27834631/fc%C3%AE-riib-ship2-axis-links-a%C3%AE-to-tau-pathology-by-disrupting-phosphoinositide-metabolism-in-alzheimer-s-disease-model
#3
Tae-In Kam, Hyejin Park, Youngdae Gwon, Sungmin Song, Seo-Hyun Kim, Seo Won Moon, Dong-Gyu Jo, Yong-Keun Jung
Amyloid-β (Aβ)-containing extracellular plaques and hyperphosphorylated tau-loaded intracellular neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease (AD). Although Aβ exerts neuropathogenic activity through tau, the mechanistic link between Aβ and tau pathology remains unknown. Here, we showed that the FcγRIIb-SHIP2 axis is critical in Aβ1-42-induced tau pathology. Fcgr2b knockout or antagonistic FcγRIIb antibody inhibited Aβ1-42-induced tau hyperphosphorylation and rescued memory impairments in AD mouse models...
November 11, 2016: ELife
https://www.readbyqxmd.com/read/27804871/the-sam-domain-of-epha2-receptor-and-its-relevance-to-cancer-a-novel-challenge-for-drug-discovery
#4
Flavia Mercurio, Marilisa Leone
BACKGROUND: Eph receptors play important functions in developmental processes and diseases and among them EphA2 is well known for its controversial role in cancer. Drug discovery strategies are mainly centered on EphA2 extracellular ligand-binding domain however, the receptor also contains a largely unexplored cytosolic Sam (Sterile alpha motif) domain at the C-terminus. EphA2-Sam binds the Sam domain from the lipid phosphatase Ship2 and the first Sam domain of Odin. Sam-Sam interactions may be important to regulate ligand-induced receptor endocytosis and degradation i...
November 1, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27716613/lipid-phosphatase-ship2-functions-as-oncogene-in-colorectal-cancer-by-regulating-pkb-activation
#5
Elmer Hoekstra, Asha M Das, Marcella Willemsen, Marloes Swets, Peter J K Kuppen, Christien J van der Woude, Marco J Bruno, Jigisha P Shah, Timo L M Ten Hagen, John D Chisholm, William G Kerr, Maikel P Peppelenbosch, Gwenny M Fuhler
Colorectal cancer (CRC) is the second most common cause of cancer-related death, encouraging the search for novel therapeutic targets affecting tumor cell proliferation and migration. These cellular processes are under tight control of two opposing groups of enzymes; kinases and phosphatases. Aberrant activity of kinases is observed in many forms of cancer and as phosphatases counteract such "oncogenic" kinases, it is generally assumed that phosphatases function as tumor suppressors. However, emerging evidence suggests that the lipid phosphatase SH2-domain-containing 5 inositol phosphatase (SHIP2), encoded by the INPPL1 gene, may act as an oncogene...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27708270/inppl1-gene-mutations-in-opsismodysplasia
#6
Anaïs Fradet, Jamie Fitzgerald
The INPPL1 (inositol polyphosphate phosphatase-like 1) gene encodes the inositol phosphatase, SHIP2 (for src homology 2 domain-containing inositol phosphatase 2). SHIP2 functions to dephosphorylate, and negatively regulate, the lipid second messenger phosphatidylinositol (3,4,5)P3. SHIP2 has been well studied in the area of insulin resistance and obesity but has roles in cancer and other disorders. Recently, it was reported that mutations in INPPL1 cause opsismodysplasia, a rare, autosomal recessive severe skeletal dysplasia...
October 6, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27597754/5-inositol-phosphatase-ship2-recruits-mena-to-stabilize-invadopodia-for-cancer-cell-invasion
#7
Charles V Rajadurai, Serhiy Havrylov, Paula P Coelho, Colin D H Ratcliffe, Kossay Zaoui, Bruce H Huang, Anie Monast, Naila Chughtai, Veena Sangwan, Frank B Gertler, Peter M Siegel, Morag Park
Invadopodia are specialized membrane protrusions that support degradation of extracellular matrix (ECM) by cancer cells, allowing invasion and metastatic spread. Although early stages of invadopodia assembly have been elucidated, little is known about maturation of invadopodia into structures competent for ECM proteolysis. The localized conversion of phosphatidylinositol(3,4,5)-triphosphate and accumulation of phosphatidylinositol(3,4)-bisphosphate at invadopodia is a key determinant for invadopodia maturation...
September 12, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27246739/the-ship2-interactor-myo1c-is-required-for-cell-migration-in-1321-n1-glioblastoma-cells
#8
William's Elong Edimo, Ana Raquel Ramos, Somadri Ghosh, Jean-Marie Vanderwinden, Christophe Erneux
The phosphoinositide 5-phosphatases consist of several enzymes that have been shown to modulate cell migration and invasion. SHIP2, one family member, is known to interact with growth factor receptors and cytoskeletal proteins. In a human model of glioblastoma 1321 N1 cells, we recently identified Myo1c as a new interactor of SHIP2. This was shown in a complex of proteins also containing filamin A. We show here that SHIP2 localization at lamellipodia and ruffles is impaired in Myo1c depleted cells. In the absence of Myo1c, N1 cells tend to associate to form clusters...
August 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27233067/novel-compound-heterozygous-mutations-in-inositol-polyphosphate-phosphatase-like-1-in-a-family-with-severe-opsismodysplasia
#9
Cori Feist, Paul Holden, Jamie Fitzgerald
This study aimed to identify the genetic basis of a severe skeletal lethal dysplasia. The main clinical features of two affected fetuses included short limbs with flared metaphyses, bowed radii, femora and tibiae, irregular ossification of hands and feet, and marked platyspondyly. Affected and nonaffected family members were subjected to whole-exome sequencing, followed by immunoblot analysis on amniocytes isolated from one of the affected individuals. Unique compound heterozygous variants in the inositol polyphosphate phosphatase-like 1 (INPPL1) gene encoding the SHIP2 protein were identified in both affected individuals...
October 2016: Clinical Dysmorphology
https://www.readbyqxmd.com/read/27170292/expression-purification-crystallisation-and-x-ray-crystallographic-analysis-of-a-truncated-form-of-human-src-homology-2-containing-inositol-5-phosphatase-2
#10
Johanne Le Coq, Luis Heredia Gallego, Daniel Lietha
The Src homology 2 containing inositol 5-phosphatase 2 (SHIP2) catalyses the dephosphorylation of the phospholipid phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3) to form PI(3,4)P2. PI(3,4,5)P3 is a key lipid second messenger, which can recruit signalling proteins to the plasma membrane and subsequently initiate numerous downstream signalling pathways responsible for the regulation of a plethora of cellular events such as proliferation, growth, apoptosis and cytoskeletal rearrangements. SHIP2 has been heavily implicated with several serious diseases such as cancer and type 2 diabetes but its regulation remains poorly understood...
June 2016: Protein Journal
https://www.readbyqxmd.com/read/26910424/dissociation-of-a-dynamic-protein-complex-studied-by-all-atom-molecular-simulations
#11
Liqun Zhang, Susmita Borthakur, Matthias Buck
The process of protein complex dissociation remains to be understood at the atomic level of detail. Computers now allow microsecond timescale molecular-dynamics simulations, which make the visualization of such processes possible. Here, we investigated the dissociation process of the EphA2-SHIP2 SAM-SAM domain heterodimer complex using unrestrained all-atom molecular-dynamics simulations. Previous studies on this system have shown that alternate configurations are sampled, that their interconversion can be fast, and that the complex is dynamic by nature...
February 23, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/26510503/angiotensin-ii-down-regulates-nephrin-akt-signaling-and-induces-podocyte-injury-roleof-c-abl
#12
Qian Yang, Yiqiong Ma, Yipeng Liu, Wei Liang, Xinghua Chen, Zhilong Ren, Huiming Wang, Pravin C Singhal, Guohua Ding
Recent studies have shown that nephrin plays a vital role in angiotensin II (Ang II)-induced podocyte injury and thus contributes to the onset of proteinuria and the progression of renal diseases, but its specific mechanism remains unclear. c-Abl is an SH2/SH3 domain-containing nonreceptor tyrosine kinase that is involved in cell survival and regulation of the cytoskeleton. Phosphorylated nephrin is able to interact with molecules containing SH2/SH3 domains, suggesting that c-Abl may be a downstream molecule of nephrin signaling...
January 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/26456051/sh2-domain-containing-inositol-5-phosphatase-ship2-inhibition-ameliorates-high-glucose-induced-de-novo-lipogenesis-and-vldl-production-through-regulating-ampk-mtor-srebp1-pathway-and-ros-production-in-hepg2-cells
#13
Sattar Gorgani-Firuzjaee, Reza Meshkani
Hepatic de-novo lipogenesis and production of triglyceride rich very low density lipoprotein (VLDL) is increased in the state of insulin resistance, however, the role of a negative regulator of the insulin signaling pathway, the SH2 domain-containing inositol 5-phosphatase (SHIP2) in this process, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to metabolic dyslipidemia using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to high glucose (33 mM)...
December 2015: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/26337385/ptp1b-dependent-regulation-of-receptor-tyrosine-kinase-signaling-by-the-actin-binding-protein-mena
#14
Shannon K Hughes, Madeleine J Oudin, Jenny Tadros, Jason Neil, Amanda Del Rosario, Brian A Joughin, Laila Ritsma, Jeff Wyckoff, Eliza Vasile, Robert Eddy, Ulrike Philippar, Alisha Lussiez, John S Condeelis, Jacco van Rheenen, Forest White, Douglas A Lauffenburger, Frank B Gertler
During breast cancer progression, alternative mRNA splicing produces functionally distinct isoforms of Mena, an actin regulator with roles in cell migration and metastasis. Aggressive tumor cell subpopulations express Mena(INV), which promotes tumor cell invasion by potentiating EGF responses. However, the mechanism by which this occurs is unknown. Here we report that Mena associates constitutively with the tyrosine phosphatase PTP1B and mediates a novel negative feedback mechanism that attenuates receptor tyrosine kinase signaling...
November 1, 2015: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/26201869/suppression-of-ship2-contributes-to-tumorigenesis-and-proliferation-of-gastric-cancer-cells-via-activation-of-akt
#15
Yan Ye, Yan Mei Ge, Miao Miao Xiao, Li Mei Guo, Qun Li, Ji Qing Hao, Jie Da, Wang Lai Hu, Xu Dong Zhang, Jiegou Xu, Lin Jie Zhang
BACKGROUND: The Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is implicated in diabetes, arthrosclerosis, and cancer. However, the role of SHIP2 in human gastric cancer remains unclear. METHODS: The expression levels of SHIP2 in gastric cancer tissues, a panel of gastric cancer cell lines, and normal gastric epithelial cells were analyzed by immunohistochemistry (IHC), Western blot, and real-time quantitative RT-PCR (qRT-PCR). Gastric cancer cells with either overexpressed SHIP2 or co-overexpressed SHIP2 and Akt were analyzed to determine cell proliferation, colony formation, apoptosis, cell migration, and invasion assays...
March 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/26188518/sh2-domain-containing-inositol-5-phosphatase-ship2-regulates-de-novo-lipogenesis-and-secretion-of-apob100-containing-lipoproteins-in-hepg2-cells
#16
Sattar Gorgani-Firuzjaee, Shohreh Khatami, Khosrow Adeli, Reza Meshkani
Hepatic de-novo lipogenesis and production of triglyceride rich VLDL are regulated via the phosphoinositide 3-kinase cascade, however, the role of a negative regulator of this pathway, the SH2 domain-containing inositol 5-phosphatase (SHIP2) in this process, remains unknown. In the present study, we investigated the molecular link between SHIP2 expression and metabolic dyslipidemia using overexpression or suppression of SHIP2 gene in HepG2 cells. The results showed that overexpression of the wild type SHIP2 gene (SHIP2-WT) led to a higher total lipid content (28%) compared to control, whereas overexpression of the dominant negative SHIP2 gene (SHIP2-DN) reduced total lipid content in oleate treated cells by 40%...
September 4, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26123392/inhibition-of-sh2-domain-containing-inositol-5-phosphatase-ship2-ameliorates-palmitate-induced-apoptosis-through-regulating-akt-foxo1-pathway-and-ros-production-in-hepg2-cells
#17
Sattar Gorgani-Firuzjaee, Khosrow Adeli, Reza Meshkani
The serine-threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome c and poly (ADP-ribose) polymerase...
August 21, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26064210/ship2-on-pi3k-akt-pathway-in-palmitic-acid-stimulated-islet-%C3%AE-cell
#18
Qingjuan Liu, Ruiying Wang, Hong Zhou, Lihui Zhang, Yanping Cao, Xianjuan Wang, Yongmei Hao
This study is to investigate the influence of SHIP2 on palmitic acid stimulated islet β cell and insulin secretion, as well as its role in pI3K/Akt pathway. We defined four groups: control, acid group, acid + NC siRNA group and acid + siRNA transfection group. The control was neither treated by palmitic acid nor transfection. The acid group was subjected to palmitic acid incubation. The acid + NC siRNA group was transiently transfected by NC siRNA, then was stimulated by palmitic acid. The acid + siRNA group was transiently transfected by siRNA, then was stimulated by palmitic acid...
2015: International Journal of Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/25635986/single-nucleotide-polymorphisms-on-ship2-is-associated-with-type-2-diabetes-mellitus-in-chinese-han-population
#19
Y-M Hao, Q-J Liu, R-Y Wang, Y-P Cao, Y Zhang, L-F Zuo
OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance in the target tissue of insulin with insufficient insulin secretion in pancreatic β-cells. Src homology 2-containing 5'-inositol phosphatase 2 (SHIP2) is a lipid phosphatase that hydrolyzes PI3-kinase product PI(3,4,5)P3 to PI(3,4)P2, which contributes to the negative regulation of insulin signaling both in vitro and in vivo. Some polymorphisms of SHIP2 have been reported to be associated with the metabolic syndrome including T2DM and hypertension in British, French and Japanese T2DM population...
January 2015: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/25525286/high-ship2-expression-indicates-poor-survival-in-colorectal-cancer
#20
Ju Yang, Maoying Fu, Yaoguang Ding, Yajing Weng, Weifei Fan, Xiaolin Pu, Zhijun Ge, Feng Zhan, Huihui Ni, Wei Zhang, Feng Jin, Ning Xu, Jiang Li, Liang Qiu, Jun Wang, Xuefeng Gu
SH2-containing inositol 5'-phosphatase 2 (SHIP2), which generally regulates insulin signaling, cytoskeleton remodeling, and receptor endocytosis, has been suggested to play a significant role in tumor development and progression. However, the associations between SHIP2 expression and the clinical features to evaluate its clinicopathologic significance in colorectal cancer (CRC) have not been determined yet. In the present study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with CRC tissue microarrays (TMA) were employed to evaluate the mRNA and protein expression of SHIP2 in CRC...
2014: Disease Markers
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