The Experts below are selected from a list of 102 Experts worldwide ranked by ideXlab platform
Hong-chen Chen - One of the best experts on this subject based on the ideXlab platform.
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Phosphorylation of moesin by Jun N-terminal kinase is important for podosome Rosette Formation in Src-transformed fibroblasts
Journal of Cell Science, 2013Co-Authors: Yi-ru Pan, Wei-shan Tseng, Po-wei Chang, Hong-chen ChenAbstract:Summary Podosomes are actin-based membrane protrusions that facilitate extracellular matrix degradation and motility of invasive cells. Podosomes can self-organize into large Rosette-like structures in Src-transformed fibroblasts, osteoclasts and some highly invasive cancer cells. However, the mechanism of this assembly remains obscure. In this study, we show that the suppression of Jun N-terminal kinase (JNK) by the JNK inhibitor SP600125 or short-hairpin RNA inhibited podosome Rosette Formation in SrcY527F-transformed NIH3T3 fibroblasts. In addition, SrcY527F was less able to induce podosome Rosettes in JNK1-null or JNK2-null mouse embryo fibroblasts than in wild-type counterparts. The kinase activity of JNK was essential for promoting podosome Rosette Formation but not for its localization to podosome Rosettes. Moesin, a member of the ERM (ezrin, radixin and moesin) protein family, was identified as a substrate of JNK. We show that the phosphorylation of moesin at Thr558 by JNK was important for podosome Rosette Formation in SrcY527F-transformed NIH3T3 fibroblasts. Taken together, our results unveil a novel role of JNK in podosome Rosette Formation through the phosphorylation of moesin.
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Protein tyrosine phosphatase SHP2 suppresses podosome Rosette Formation in Src-transformed fibroblasts.
Journal of Cell Science, 2012Co-Authors: Yi-ru Pan, Ke-huan Cho, Hsiao-hui Lee, Zee-fen Chang, Hong-chen ChenAbstract:Podosomes are actin-enriched membrane protrusions that play important roles in extracellular matrix degradation and invasive cell motility. Podosomes undergo self-assembly into large Rosette-like structures in Src-transformed fibroblasts, osteoclasts and certain highly invasive cancer cells. Several protein tyrosine kinases have been shown to be important for the Formation of podosome Rosettes, but little is known regarding the role of protein tyrosine phosphatases in this process. We found that knockdown of the Src homolog domain-containing phosphatase 2 (SHP2) significantly increased podosome Rosette Formation in Src-transformed fibroblasts. By contrast, SHP2 overexpression suppressed podosome Rosette Formation in these cells. The phosphatase activity of SHP2 was essential for the suppression of podosome Rosette Formation. SHP2 selectively suppressed the tyrosine phosphorylation of Tks5, a scaffolding protein required for podosome Formation. The inhibitory effect of SHP2 on podosome Rosette Formation was associated with the increased activation of Rho-associated kinase (ROCK) and the enhanced polymerization of vimentin filaments. A higher content of polymerized vimentin filaments was correlated with a lower content of podosome Rosettes. Taken together, our findings indicate that SHP2 serves as a negative regulator of podosome Rosette Formation through the dephosphorylation of Tks5 and the activation of ROCK-mediated polymerization of vimentin in Src-transformed fibroblasts.
Yi-ru Pan - One of the best experts on this subject based on the ideXlab platform.
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Phosphorylation of moesin by Jun N-terminal kinase is important for podosome Rosette Formation in Src-transformed fibroblasts
Journal of Cell Science, 2013Co-Authors: Yi-ru Pan, Wei-shan Tseng, Po-wei Chang, Hong-chen ChenAbstract:Summary Podosomes are actin-based membrane protrusions that facilitate extracellular matrix degradation and motility of invasive cells. Podosomes can self-organize into large Rosette-like structures in Src-transformed fibroblasts, osteoclasts and some highly invasive cancer cells. However, the mechanism of this assembly remains obscure. In this study, we show that the suppression of Jun N-terminal kinase (JNK) by the JNK inhibitor SP600125 or short-hairpin RNA inhibited podosome Rosette Formation in SrcY527F-transformed NIH3T3 fibroblasts. In addition, SrcY527F was less able to induce podosome Rosettes in JNK1-null or JNK2-null mouse embryo fibroblasts than in wild-type counterparts. The kinase activity of JNK was essential for promoting podosome Rosette Formation but not for its localization to podosome Rosettes. Moesin, a member of the ERM (ezrin, radixin and moesin) protein family, was identified as a substrate of JNK. We show that the phosphorylation of moesin at Thr558 by JNK was important for podosome Rosette Formation in SrcY527F-transformed NIH3T3 fibroblasts. Taken together, our results unveil a novel role of JNK in podosome Rosette Formation through the phosphorylation of moesin.
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Protein tyrosine phosphatase SHP2 suppresses podosome Rosette Formation in Src-transformed fibroblasts.
Journal of Cell Science, 2012Co-Authors: Yi-ru Pan, Ke-huan Cho, Hsiao-hui Lee, Zee-fen Chang, Hong-chen ChenAbstract:Podosomes are actin-enriched membrane protrusions that play important roles in extracellular matrix degradation and invasive cell motility. Podosomes undergo self-assembly into large Rosette-like structures in Src-transformed fibroblasts, osteoclasts and certain highly invasive cancer cells. Several protein tyrosine kinases have been shown to be important for the Formation of podosome Rosettes, but little is known regarding the role of protein tyrosine phosphatases in this process. We found that knockdown of the Src homolog domain-containing phosphatase 2 (SHP2) significantly increased podosome Rosette Formation in Src-transformed fibroblasts. By contrast, SHP2 overexpression suppressed podosome Rosette Formation in these cells. The phosphatase activity of SHP2 was essential for the suppression of podosome Rosette Formation. SHP2 selectively suppressed the tyrosine phosphorylation of Tks5, a scaffolding protein required for podosome Formation. The inhibitory effect of SHP2 on podosome Rosette Formation was associated with the increased activation of Rho-associated kinase (ROCK) and the enhanced polymerization of vimentin filaments. A higher content of polymerized vimentin filaments was correlated with a lower content of podosome Rosettes. Taken together, our findings indicate that SHP2 serves as a negative regulator of podosome Rosette Formation through the dephosphorylation of Tks5 and the activation of ROCK-mediated polymerization of vimentin in Src-transformed fibroblasts.
Rachanee Udomsangpetch - One of the best experts on this subject based on the ideXlab platform.
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effects of sevuparin on Rosette Formation and cytoadherence of plasmodium falciparum infected erythrocytes
PLOS ONE, 2017Co-Authors: Somporn Saiwaew, Rachanee Udomsangpetch, Juntima Sritabal, Nattaporn Piaraksa, Srisuda Keayarsa, Ronnatrai Ruengweerayut, Chirapong Utaisin, Patima Sila, Rangsan Niramis, Prakaykaew CharunwatthanaAbstract:In severe falciparum malaria cytoadherence of parasitised red blood cells (PRBCs) to vascular endothelium (causing sequestration) and to uninfected red cells (causing Rosette Formation) contribute to microcirculatory flow obstruction in vital organs. Heparin can reverse the underlying ligand-receptor interactions, but may increase the bleeding risks. As a heparin-derived polysaccharide, sevuparin has been designed to retain anti-adhesive properties, while the antithrombin-binding domains have been eliminated, substantially diminishing its anticoagulant activity. Sevuparin has been evaluated recently in patients with uncomplicated falciparum malaria, and is currently investigated in a clinical trial for sickle cell disease. The effects of sevuparin on Rosette Formation and cytoadherence of Plasmodium falciparum isolates from Thailand were investigated. Trophozoite stages of P. falciparum-infected RBCs (Pf-iRBCs) were cultured from 49 patients with malaria. Pf-iRBCs were treated with sevuparin at 37°C and assessed in rosetting and in cytoadhesion assays with human dermal microvascular endothelial cells (HDMECs) under static and flow conditions. The proportion of Pf-iRBCs forming Rosettes ranged from 6.5% to 26.0% (median = 12.2%). Rosetting was dose dependently disrupted by sevuparin (50% disruption by 250 μg/mL). Overall 57% of P. falciparum isolates bound to HDMECs under static conditions; median (interquartile range) Pf-iRBC binding was 8.5 (3.0-38.0) Pf-iRBCs/1000 HDMECs. Sevuparin in concentrations ≥ 100 μg/mL inhibited cytoadherence. Sevuparin disrupts P. falciparum Rosette Formation in a dose dependent manner and inhibits cytoadherence to endothelial cells. The data support assessment of sevuparin as an adjunctive treatment to the standard therapy in severe falciparum malaria.
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short report Rosette Formation in plasmodium ovale infection
American Journal of Tropical Medicine and Hygiene, 1996Co-Authors: Brian Angus, Kamolrat Silamut, Nicholas J. White, Kesinee Thanikkul, Rachanee UdomsangpetchAbstract:Red blood cells infected by mature stages of Plasmodium ovale obtained from a 56-year-old Thai patient formed Rosettes readily with uninfected erythrocytes. Ex vivo, the ring stage-infected erythrocytes matured well under the in vitro conditions used for P. falciparum culture, and the infected erythrocytes formed Rosettes when the parasites became mature trophozoites. These Rosettes were stable and remained intact until completion of schizogony. Plasmodium ovale Rosettes were similar to those formed by P. falciparum- and P. vivax-infected erythrocytes. Rosette Formation appears to be a common property of three species of human plasmodia.
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Rosette Formation by plasmodium coatneyi infected red blood cells
American Journal of Tropical Medicine and Hygiene, 1991Co-Authors: Rachanee Udomsangpetch, Arthur Brown, C D Smith, H K WebsterAbstract:Animal models are needed for the study of cytoadherence in falciparum malaria. Red blood cell (RBC) Rosette Formation is one type of cytoadherence and appears to be associated with knob Formation, endothelial cell adhesion and sequestration of Plasmodium-infected RBCs. Since Plasmodium coatneyi-infected RBCs develop knobs and sequester, we hypothesized that they also form Rosettes. RBCs from P. coatneyi-infected rhesus monkeys (Macaca-mulatta) were collected, allowed to mature overnight in vitro and found to form Rosettes as hypothesized. This observation adds to the known falciparum-like characteristics of P. coatneyi, and suggests that the Macaca mulatta-P. coatneyi model may be appropriate for pathophysiologic studies of cytoadherence.
Christopher E. Turner - One of the best experts on this subject based on the ideXlab platform.
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Hic-5 regulates Src-induced invadopodia Rosette Formation and organization.
Molecular Biology of the Cell, 2019Co-Authors: Anushree C. Gulvady, Ian J. Forsythe, Christopher E. TurnerAbstract:Fibroblasts transformed by the proto-oncogene Src form individual invadopodia that can spontaneously self-organize into large matrix-degrading superstructures called Rosettes. However, the mechanisms by which the invadopodia can spatiotemporally reorganize their architecture is not well understood. Here, we show that Hic-5, a close relative of the scaffold protein paxillin, is essential for the Formation and organization of Rosettes in active Src-transfected NIH3T3 fibroblasts and cancer-associated fibroblasts. Live cell imaging, combined with domain-mapping analysis of Hic-5, identified critical motifs as well as phosphorylation sites that are required for the Formation and dynamics of Rosettes. Using pharmacological inhibition and mutant expression, we show that FAK kinase activity, along with its proximity to and potential interaction with the LD2,3 motifs of Hic-5, is necessary for Rosette Formation. Invadopodia dynamics and their coalescence into Rosettes were also dependent on Rac1, formin, and myosin II activity. Superresolution microscopy revealed the presence of formin FHOD1 and INF2-mediated unbranched radial F-actin fibers emanating from invadopodia and Rosettes, which may facilitate Rosette Formation. Collectively, our data highlight a novel role for Hic-5 in orchestrating the organization of invadopodia into higher-order Rosettes, which may promote the localized matrix degradation necessary for tumor cell invasion.
Nicholas J. White - One of the best experts on this subject based on the ideXlab platform.
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short report Rosette Formation in plasmodium ovale infection
American Journal of Tropical Medicine and Hygiene, 1996Co-Authors: Brian Angus, Kamolrat Silamut, Nicholas J. White, Kesinee Thanikkul, Rachanee UdomsangpetchAbstract:Red blood cells infected by mature stages of Plasmodium ovale obtained from a 56-year-old Thai patient formed Rosettes readily with uninfected erythrocytes. Ex vivo, the ring stage-infected erythrocytes matured well under the in vitro conditions used for P. falciparum culture, and the infected erythrocytes formed Rosettes when the parasites became mature trophozoites. These Rosettes were stable and remained intact until completion of schizogony. Plasmodium ovale Rosettes were similar to those formed by P. falciparum- and P. vivax-infected erythrocytes. Rosette Formation appears to be a common property of three species of human plasmodia.
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Rosette Formation of Plasmodium falciparum-infected erythrocytes from patients with acute malaria.
Infection and immunity, 1991Co-Authors: T. M. E. Davis, Kamolrat Silamut, Danai Bunnag, Nicholas J. WhiteAbstract:Noninfected erythrocytes form Rosettes around those infected with trophozoites and schizonts of Plasmodium falciparum in vitro. These Rosettes are thought to contribute to the microvascular obstruction which underlies the pathophysiology of severe falciparum malaria. To determine whether the percentage of infected erythrocytes forming Rosettes for a parasite isolates in vitro correlates with the in vivo severity of disease, we studied the Rosette Formation behavior of 35 isolates of P. falciparum from patients with uncomplicated, severe, and cerebral malaria. There was a wide variation in the degree of Rosette Formation (0 to 53%). Four parasite isolates formed Rosettes well (30 to 53%), and seven isolates formed Rosettes poorly or not at all (0 to 5%), while the majority of the isolates formed Rosettes to various degrees between these two extremes. In this relatively small sample of patients, we were unable to demonstrate a significant association between in vitro Rosette Formation and patients with cerebral malaria or conscious patients with significant renal (serum creatinine greater than 200 mumol/liter) or hepatic dysfunction (serum bilirubin greater than 50 mumol/liter and aspartate aminotransferase greater than 50 Reitman-Frankel units). However, there was an inverse relationship between Rosette Formation and cytoadherence (r = -0.575, P less than 0.01) which could not be explained on the basis of steric hindrance. This finding suggests that cytoadherence and Rosette Formation properties are intrinsic to the parasites, with isolates having a greater propensity for one or the other but not both. Further studies are required to establish the occurrence and pathophysiological role of Rosette Formation in vivo.
