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https://www.readbyqxmd.com/read/29749928/specific-eph-receptor-cytoplasmic-effector-signaling-mediated-by-sam-sam-domain-interactions
#1
Yue Wang, Yuan Shang, Jianchao Li, Weidi Chen, Gang Li, Jun Wan, Wei Liu, Mingjie Zhang
The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern...
May 11, 2018: ELife
https://www.readbyqxmd.com/read/29416010/role-of-c-abl-and-nephrin-in-podocyte-cytoskeletal-remodeling-induced-by-angiotensin-ii
#2
Yiqiong Ma, Qian Yang, Zhentong Zhong, Wei Liang, Lu Zhang, Yingjie Yang, Guohua Ding
Our previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies showed that nephrin was required for cytoskeletal remodeling in glomerular podocytes. But its specific mechanisms remain incompletely understood. As a nonreceptor tyrosine kinase involved in cytoskeletal regulation, c-Abl may be a candidate of signaling proteins interacting with Src homology 2/3 (SH2/SH3) domains of nephrin...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29234063/the-sam-sam-interaction-between-ship2-and-the-epha2-receptor-design-and-analysis-of-peptide-inhibitors
#3
Flavia Anna Mercurio, Concetta Di Natale, Luciano Pirone, Roberta Iannitti, Daniela Marasco, Emilia Maria Pedone, Rosanna Palumbo, Marilisa Leone
The lipid phosphatase Ship2 represents a drug discovery target for the treatment of different diseases, including cancer. Its C-terminal sterile alpha motif domain (Ship2-Sam) associates with the Sam domain from the EphA2 receptor (EphA2-Sam). This interaction is expected to mainly induce pro-oncogenic effects in cells therefore, inhibition of the Ship2-Sam/EphA2-Sam complex may represent an innovative route to discover anti-cancer therapeutics. In the present work, we designed and analyzed several peptide sequences encompassing the interaction interface of EphA2-Sam for Ship2-Sam...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228424/circulating-ship2-mrna-as-a-novel-biomarker-in-the-diagnosis-and-prognosis-of-gastric-cancer
#4
J-F Xie, N-S Xie, J-H Tang, Q-P Gu, Q-T Luo
OBJECTIVE: Previous studies showed the aberrant expression of Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) in GC tissue. However, the exact role of circulating SHIP2 in GC remains unclear. The aim of this manuscript was to analyze potential diagnostic and prognostic value of circulating SHIP2 levels in GC. PATIENTS AND METHODS: Circulating SHIP2 expression was detected in the plasma of 156 GC patients and 60 healthy controls by qRT-PCR. The receiver operating characteristic (ROC) curves were plotted to explore the reliability of circulating SHIP2 in detecting GC...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29068796/protein-phosphatases-and-podocyte-function
#5
Pedro Geraldes
PURPOSE OF REVIEW: Deregulation of protecting factor signaling actions in podocytes has emerged as an alternative pathway of podocyte injury mechanisms. Here, we review recent knowledge that highlighted how podocyte protecting factors are modulated by protein phosphatases. RECENT FINDINGS: Protein tyrosine kinases and phosphatases participate in many, if not all, aspects of cellular function by turning on or off multiple signaling cascades and podocytes are no exception...
January 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29030113/proteomic-analyses-of-signalling-complexes-associated-with-receptor-tyrosine-kinase-identify-novel-members-of-fibroblast-growth-factor-receptor-3-interactome
#6
Lukas Balek, Pavel Nemec, Peter Konik, Michaela Kunova Bosakova, Miroslav Varecha, Iva Gudernova, Jirina Medalova, Deborah Krakow, Pavel Krejci
Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. A single tag immunoprecipitation and phosphotyrosine protein isolation followed by mass-spectrometry was used to identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3)...
January 2018: Cellular Signalling
https://www.readbyqxmd.com/read/28916189/phosphoinositide-5-phosphatase-activities-control-cell-motility-in-glioblastoma-two-phosphoinositides-pi-4-5-p2-and-pi-3-4-p2-are-involved
#7
REVIEW
Ana Raquel Ramos, William's Elong Edimo, Christophe Erneux
Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes...
January 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28878342/inhibition-of-ship2-in-cd2ap-deficient-podocytes-ameliorates-reactive-oxygen-species-generation-but-aggravates-apoptosis
#8
Pauliina Saurus, Tuomas A Tolvanen, Sonja Lindfors, Sara Kuusela, Harry Holthöfer, Eero Lehtonen, Sanna Lehtonen
Lack of CD2-associated protein (CD2AP) in mice increases podocyte apoptosis and leads to glomerulosclerosis and renal failure. We showed previously that SHIP2, a negative regulator of the PI3K/AKT signalling pathway, interacts with CD2AP. Here, we found that the expression level and activity of SHIP2 and production of reactive oxygen species (ROS) are increased in cultured CD2AP knockout (CD2AP-/-) mouse podocytes. Oxidative stress was also increased in CD2AP-/- mouse glomeruli in vivo. We found that puromycin aminonucleoside (PA), known to increase ROS production and apoptosis, increases SHIP2 activity and reduces CD2AP expression in cultured human podocytes...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28869677/fibroblasts-derived-from-patients-with-opsismodysplasia-display-ship2-specific-cell-migration-and-adhesion-defects
#9
Somadri Ghosh, Céline Huber, Quentin Siour, Sérgio B Sousa, Michael Wright, Valérie Cormier-Daire, Christophe Erneux
The SH2 domain containing inositol phosphatase 2 (SHIP2) dephosphorylates PI(3,4,5)P3 to generate PI(3,4)P2, a lipid involved in the control of cell migration and adhesion. The INPPL1 gene that encodes SHIP2 has been found to be mutated in several cases of opsismodysplasia (OPS), a rare autosomal recessive chondrodysplasia characterized by growth plate defects and delayed bone maturation. Reported mutations often result in premature stop codons or missense mutations in SHIP2 catalytic domain. SHIP2 biochemical properties are known from studies in cancer cells; its role in endochondral ossification is unknown...
September 4, 2017: Human Mutation
https://www.readbyqxmd.com/read/28857346/zic2-promotes-viability-and-invasion-of-human-osteosarcoma-cells-by-suppressing-ship2-expression-and-activating-pi3k-akt-pathways
#10
Shuaihao Huang, Anmin Jin
Osteosarcoma is a malignant tumor of the skeletal system. The zinc finger transcription factor ZIC2 has been reported to be highly expressed in human cancers. The present study evaluated the effects of ZIC2 and the possible underlying mechanisms in the human osteosarcoma cells. The expression levels of ZIC2 in human fetal osteoblastic cell line (hFOB1.19), osteosarcoma cell lines (U-2OS, SaoS2, and MG63), normal bone tissue, and osteosarcoma tumor were analyzed by Western blot, and real-time quantitative RT-PCR (qRT-PCR)...
February 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28830894/endothelial-ship2-suppresses-nox2-nadph-oxidase-dependent-vascular-oxidative-stress-endothelial-dysfunction-and-systemic-insulin-resistance
#11
Nicole T Watt, Matthew C Gage, Peysh A Patel, Hema Viswambharan, Piruthivi Sukumar, Stacey Galloway, Nadira Y Yuldasheva, Helen Imrie, Andrew M N Walker, Kathryn J Griffin, Natalia Makava, Anna Skromna, Katherine Bridge, David J Beech, Stéphane Schurmans, Stephen B Wheatcroft, Mark T Kearney, Richard M Cubbon
Shc homology 2-containing inositol 5' phosphatase-2 (SHIP2) is a lipid phosphatase that inhibits insulin signaling downstream of phosphatidylinositol 3-kinase (PI3K); its role in vascular function is poorly understood. To examine its role in endothelial cell (EC) biology, we generated mice with catalytic inactivation of one SHIP2 allele selectively in ECs (ECSHIP2Δ/+ ). Hyperinsulinemic-euglycemic clamping studies revealed that ECSHIP2Δ/+ was resistant to insulin-stimulated glucose uptake in adipose tissue and skeletal muscle compared with littermate controls...
November 2017: Diabetes
https://www.readbyqxmd.com/read/28792888/structural-basis-for-interdomain-communication-in-ship2-providing-high-phosphatase-activity
#12
Johanne Le Coq, Marta Camacho-Artacho, José Vicente Velázquez, Clara M Santiveri, Luis Heredia Gallego, Ramón Campos-Olivas, Nicole Dölker, Daniel Lietha
SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) and play important roles in regulating the PI3K/Akt pathway in physiology and disease. Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determined crystal structures containing the 5-phosphatase and a proximal region adopting a C2 fold. This reveals an extensive interface between the two domains, which results in significant structural changes in the phosphatase domain...
August 9, 2017: ELife
https://www.readbyqxmd.com/read/28602916/structural-investigation-of-a-c-terminal-epha2-receptor-mutant-does-mutation-affect-the-structure-and-interaction-properties-of-the-sam-domain
#13
Flavia A Mercurio, Susan Costantini, Concetta Di Natale, Luciano Pirone, Stefano Guariniello, Pasqualina L Scognamiglio, Daniela Marasco, Emilia M Pedone, Marilisa Leone
Ephrin A2 receptor (EphA2) plays a key role in cancer, it is up-regulated in several types of tumors and the process of ligand-induced receptor endocytosis, followed by degradation, is considered as a potential path to diminish tumor malignancy. Protein modulators of this mechanism are recruited at the cytosolic Sterile alpha motif (Sam) domain of EphA2 (EphA2-Sam) through heterotypic Sam-Sam associations. These interactions engage the C-terminal helix of EphA2 and close loop regions (the so called End Helix side)...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28409542/inhibitory-receptor-fc%C3%AE-riib-mediates-the-effects-of-igg-on-a-phagosome-acidification-and-a-sequential-dephosphorylation-system-comprising-ships-and-inpp4a
#14
Tomohiro Segawa, Kaoru Hazeki, Kiyomi Nigorikawa, Atsuko Nukuda, Tomoki Tanizawa, Kenshiro Miyamoto, Shin Morioka, Osamu Hazeki
The relative abundance of phosphoinositide (PI) species on the phagosome membrane fluctuates over the course of phagocytosis. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 rapidly increase in the forming of the phagocytic cup, following which they disappear after sealing of the cup. In the present study, we monitored the clearance of these PI species using the enhanced green fluorescent protein-fused pleckstrin homology domain of Akt, a fluorescence probe that binds both PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in Raw 264.7 macrophages...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28302370/the-lipid-5-phoshatase-ship2-controls-renal-brush-border-ultrastructure-and-function-by-regulating-the-activation-of-erm-proteins
#15
Sufyan G Sayyed, François Jouret, Marjorie Vermeersch, David Pérez-Morga, Stéphane Schurmans
The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body homeostasis. Here, using the lipid 5-phosphatase Ship2 global knockout mice, proximal tubule-specific Ship2 knockout mice, and a proximal tubule cell model in which SHIP2 is inactivated, we show that SHIP2 is a negative regulator of microvilli formation, thereby controlling solute reabsorption by the proximal tubule...
July 2017: Kidney International
https://www.readbyqxmd.com/read/28247964/pi-3-4-p2-plays-critical-roles-in-the-regulation-of-focal-adhesion-dynamics-of-mda-mb-231-breast-cancer-cells
#16
Miki Fukumoto, Takeshi Ijuin, Tadaomi Takenawa
Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2 ) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI(3,4)P2 on focal adhesion dynamics in MDA-MB-231 basal breast cancer cells. Knockdown of SHIP2, a phosphatidylinositol 3,4,5-trisphosphatase (PIP3 ) 5-phosphatase that generates PI(3,4)P2 , in MDA-MB-231 breast cancer cells, induced the development of focal adhesions and cell spreading, leading to the suppression of invasion...
May 2017: Cancer Science
https://www.readbyqxmd.com/read/28117748/decreased-sp1-expression-mediates-downregulation-of-ship2-in-gastric-cancer-cells
#17
Yan Ye, Xue Yi Qian, Miao Miao Xiao, Yu Ling Shao, Li Mei Guo, Dong Ping Liao, Jie Da, Lin Jie Zhang, Jiegou Xu
Past studies have shown that the Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is commonly downregulated in gastric cancer, which contributes to elevated activation of PI3K/Akt signaling, proliferation and tumorigenesis of gastric cancer cells. However, the mechanisms underlying the reduced expression of SHIP2 in gastric cancer remain unclear. While gene copy number variation analysis and exon sequencing indicated the absence of genomic alterations of SHIP2, bisulfite genomic sequencing (BGS) showed promoter hypomethylation of SHIP2 in gastric cancer cells...
January 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28105255/pi3k-ship2-pten-pathway-in-cell-polarity-and-hepatitis-c-virus-pathogenesis
#18
REVIEW
Aline Awad, Ama Gassama-Diagne
Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases...
January 8, 2017: World Journal of Hepatology
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
#19
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
#20
REVIEW
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...
February 1, 2017: Chembiochem: a European Journal of Chemical Biology
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