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Girdin

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https://www.readbyqxmd.com/read/29630055/use-of-anti-phospho-girdin-antibodies-to-visualize-intestinal-tuft-cells-in-free-floating-mouse-jejunum-cryosections
#1
Yuka Mizutani, Daisuke Kuga, Machiko Iida, Kaori Ushida, Tsuyoshi Takagi, Yoshihito Tokita, Masahide Takahashi, Masato Asai
The actin binding protein girdin is a cytosolic protein that is required for actin remodeling to trigger cell migration in various tissues. Girdin is phosphorylated by both receptor and non-receptor tyrosine kinases at tyrosine 1798. Omori et al. developed site- and phosphorylation status-specific antibodies against human girdin at tyrosine-1798 (pY1798), which specifically bind to phosphorylated tyrosine-1798, but not to unphosphorylated tyrosine-1798. pY1798 antibodies have been used to specifically label tuft cells (TCs) that are present in mammalian gastrointestinal tissues, but the function of these cells is unclear...
March 21, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29538402/negative-regulation-of-amino-acid-signaling-by-mapk-regulated-4f2hc-girdin-complex
#2
Liang Weng, Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi
Amino acid signaling mediated by the activation of mechanistic target of rapamycin complex 1 (mTORC1) is fundamental to cell growth and metabolism. However, how cells negatively regulate amino acid signaling remains largely unknown. Here, we show that interaction between 4F2 heavy chain (4F2hc), a subunit of multiple amino acid transporters, and the multifunctional hub protein girders of actin filaments (Girdin) down-regulates mTORC1 activity. 4F2hc interacts with Girdin in mitogen-activated protein kinase (MAPK)- and amino acid signaling-dependent manners to translocate to the lysosome...
March 2018: PLoS Biology
https://www.readbyqxmd.com/read/29456687/girdin-protein-a-potential-metastasis-predictor-associated-with-prognosis-in-lung-cancer
#3
Zhaoyang Yang, Fang Yang, Yingli Zhang, Xin Wang, Jiong Shi, Hongjiao Wei, Fengwei Sun, Yan Yu
The present study explored the relationship between Girdin protein expression and the survival rate of patients with lung carcinoma. A total of 334 lung cancer specimens, 20 benign lung disease tissue sections and 24 fresh tissues from patients with lung carcinoma were analyzed by immunohistochemistry and western blotting. Girdin protein was expressed in 130/334 (38.93%) of the cases examined. Girdin protein expression was correlated with tumor/node/metastasis stage (P<0.001), lymph node metastasis (P=0...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29403565/cell-migration-in-microfabricated-3d-collagen-microtracks-is-mediated-through-the-prometastatic-protein-girdin
#4
Aniqua Rahman-Zaman, Shuo Shan, Cynthia A Reinhart-King
Introduction: In vivo, cancer cells can utilize tube-like microtracks formed within the extracellular matrix (ECM) of the stroma as 'highways' to escape the primary tumor, however very little is known about the molecular mechanisms that govern cell migration through these microtracks. Cell polarization and actin organization are both essential for efficient cell migration and cells are known to migrate very unidirectionally in confined spaces. In this study, we focused on understanding the role of Girdin during unidirectional migration...
February 2018: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/29259035/combination-of-cytoplasmic-and-nuclear-girdin-expression-is-an-independent-prognosis-factor-of-breast-cancer
#5
Huikun Zhang, Feng Yu, Fengxia Qin, Ying Shao, Wei Chong, Zhifang Guo, Xiaoli Liu, Li Fu, Feng Gu, Yongjie Ma
Girdin is an actin-binding protein playing key roles in the development of various carcinomas. Although online tools have predicted nuclear localization of girdin with a high probability, convincing proof has rarely been provided until now. The purpose of this study was to discover girdin's precise subcellular distribution and the potential prognostic value corresponding to its localization. The subcellular distribution of girdin was detected in a human breast cancer cell line and in >800 samples of human breast tissue by clinical pathologic analysis...
January 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29035513/when-heterotrimeric-g-proteins-are-not-activated-by-g-protein-coupled-receptors-structural-insights-and-evolutionary-conservation
#6
Vincent DiGiacomo, Arthur Marivin, Mikel Garcia-Marcos
Heterotrimeric G proteins are signal-transducing switches conserved across eukaryotes. In humans, they work as critical mediators of intercellular communication in the context of virtually any physiological process. While G protein regulation by G protein-coupled receptors (GPCRs) is well-established and has received much attention, it has become recently evident that heterotrimeric G proteins can also be activated by cytoplasmic proteins. However, this alternative mechanism of G protein regulation remains far less studied than GPCR-mediated signaling...
January 23, 2018: Biochemistry
https://www.readbyqxmd.com/read/28964333/rapid-kinetic-bret-measurements-to-monitor-g-protein-activation-by-gpcr-and-non-gpcr-proteins
#7
Marcin Maziarz, Mikel Garcia-Marcos
Heterotrimeric G proteins are central hubs of signal transduction whose activity is controlled by G protein-coupled receptors (GPCRs) as well as by a complex network of regulatory proteins. Recently, bioluminescence resonance energy transfer (BRET)-based assays have been used to monitor real-time activation of heterotrimeric G proteins in cells. Here we describe the use of a previously established BRET assay to monitor G protein activation upon GPCR stimulation and its adaptation to measure G protein activation by non-GPCR proteins, such as by cytoplasmic guanine nucleotide exchange factors (GEFs) like GIV/Girdin...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28964332/fluorescence-polarization-assays-to-measure-interactions-between-g%C3%AE-subunits-of-heterotrimeric-g-proteins-and-regulatory-motifs
#8
Marcin Maziarz, Mikel Garcia-Marcos
Fluorescence polarization (FP) is a simple and sensitive method allowing for the quantification of interactions between proteins and fluorescently tagged small molecules like peptides. Heterotrimeric G proteins are critical signal transducing molecules and their activity is controlled by a complex network of regulatory proteins. Some of these regulators have defined short motifs (<40 amino acids) that are sufficient to bind G proteins and subsequently modulate their activity. For these cases, FP represents a robust and quantitative method to characterize the G protein regulator interaction...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28819150/the-g%C3%AE-i-giv-binding-interface-is-a-druggable-protein-protein-interaction
#9
Vincent DiGiacomo, Alain Ibáñez de Opakua, Maria P Papakonstantinou, Lien T Nguyen, Nekane Merino, Juan B Blanco-Canosa, Francisco J Blanco, Mikel Garcia-Marcos
Heterotrimeric G proteins are usually activated by the guanine-nucleotide exchange factor (GEF) activity of GPCRs. However, some non-receptor proteins are also GEFs. GIV (a.k.a Girdin) was the first non-receptor protein for which the GEF activity was ascribed to a well-defined protein sequence that directly binds Gαi. GIV expression promotes metastasis and disruption of its binding to Gαi blunts the pro-metastatic behavior of cancer cells. Although this suggests that inhibition of the Gαi-GIV interaction is a promising therapeutic strategy, protein-protein interactions (PPIs) are considered poorly "druggable" targets requiring case-by-case validation...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818465/girdin-protein-expression-is-associated-with-poor-prognosis-in-patients-with-invasive-breast-cancer
#10
Jong-Sun Choi, Kyung Hee Kim, Ensel Oh, Young Kee Shin, Jinwon Seo, Seok-Hyung Kim, Sarah Park, Yoon-La Choi
Girdin is an actin-binding Akt substrate that is an integral component of the PI3K/Akt signalling pathway. However, the clinicopathological significance of Girdin expression in breast cancer has not been clarified. The purpose of this study was to characterise the clinicopathological implication of Girdin expression in breast cancer. Immunohistochemistry-based protein expression analyses of 892 human breast cancer tissues showed that Girdin was expressed in 289 (32.4%) cases. Girdin expression was significantly associated with larger tumour size, frequent lymph node invasion, advanced cancer stage, and expression of oestrogen and progesterone receptors...
August 14, 2017: Pathology
https://www.readbyqxmd.com/read/28810896/silencing-the-girdin-gene-enhances-radio-sensitivity-of-hepatocellular-carcinoma-via-suppression-of-glycolytic-metabolism
#11
Li Yu, Yifan Sun, Jingjing Li, Yan Wang, Yuxing Zhu, Yong Shi, Xiaojun Fan, Jianda Zhou, Ying Bao, Jie Xiao, Ke Cao, Peiguo Cao
BACKGROUND: Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear. METHODS: A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression...
August 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28713924/a-systematic-study-of-girdin-on-cell-proliferation-migration-and-angiogenesis-in-different-breast-cancer-subtypes
#12
Hongbin Wang, Jiajun Zhang, Ming Zhang, Li Wei, Hong Chen, Zhigao Li
Breast cancer has one of the highest incidences in females worldwide. Girdin is a novel actin‑binding protein, that induces cell migration and angiogenesis. However, a systematic study of Girdin function in distinct subtypes of breast cancer has not been reported to date. Therefore, the present study aimed to investigate the role of Girdin on cell proliferation, migration and angiogenesis in different subtypes of breast cancer. For this purpose, the breast epithelial MCF‑7, breast ductal T47D and breast metastatic MDA‑MB‑231 cancer cell lines were selected...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28390157/discs-large-homolog-5-decreases-formation-and-function-of-invadopodia-in-human-hepatocellular-carcinoma-via-girdin-and-tks5
#13
Yang Ke, Tianhao Bao, Qixin Zhou, Yan Wang, Jiayun Ge, Bimang Fu, Xuesong Wu, Haoran Tang, Zhitian Shi, Xuefen Lei, Cheng Zhang, Yuqi Tan, Haotian Chen, Zhitang Guo, Lin Wang
Invadopodium formation is a crucial early event of invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying regulation of invadopodia remain elusive. This study aimed to investigate the potential role of discs large homolog 5 (Dlg5) in invadopodium formation and function in HCC. We found that Dlg5 expression was significantly lower in human HCC tissues and cell lines than adjacent nontumor tissues and liver cells. Lower Dlg5 expression was associated with advanced stages of HCC, and poor overall and disease-free survival of HCC patients...
July 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28375676/tyrosine-phosphorylation-of-an-actin-binding-protein-girdin-specifically-marks-tuft-cells-in-human-and-mouse-gut
#14
Daisuke Kuga, Kaori Ushida, Shinji Mii, Atsushi Enomoto, Naoya Asai, Masato Nagino, Masahide Takahashi, Masato Asai
Tuft cells (TCs) are minor components of gastrointestinal epithelia, characterized by apical tufts and spool-shaped somas. The lack of reliable TC-markers has hindered the elucidation of its role. We developed site-specific and phosphorylation-status-specific antibodies against Girdin at tyrosine-1798 (pY1798) and found pY1798 immunostaining of mouse jejunum clearly depicted epithelial cells closely resembling TCs. This study aimed to validate pY1798 as a TC-marker. Double-fluorescence staining of intestines was performed with pY1798 and known TC-markers, for example, hematopoietic-prostaglandin-D-synthase (HPGDS), or doublecortin-like kinase 1 (DCLK1)...
June 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28287365/the-gaps-gefs-gdis-and%C3%A2-now-gems-new-kids-on-the-heterotrimeric-g-protein-signaling-block
#15
REVIEW
Pradipta Ghosh, Padmini Rangamani, Irina Kufareva
The canonical process of activation of heterotrimeric G proteins by G protein coupled receptors (GPCRs) is well studied. Recently, a rapidly emerging paradigm has revealed the existence of a new, non-canonical set of cytosolic G protein modulators, guanine exchange modulators (GEMs). Among G proteins regulators, GEMs are uniquely capable of initiating pleiotropic signals: these bifunctional modulators can activate cAMP inhibitory (Gi) proteins and inhibit cAMP-stimulatory (Gs) proteins through a single short evolutionarily conserved module...
April 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28218901/girdin-maintains-the-stemness-of-glioblastoma-stem-cells
#16
A Natsume, T Kato, S Kinjo, A Enomoto, H Toda, S Shimato, F Ohka, K Motomura, Y Kondo, T Miyata, M Takahashi, T Wakabayashi
No abstract text is available yet for this article.
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28209925/the-stress-polarity-pathway-ampk-giv-es-protection-against-metabolic-insults
#17
REVIEW
Pradipta Ghosh
Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis...
February 15, 2017: Aging
https://www.readbyqxmd.com/read/27998773/scutellarin-suppresses-migration-and-invasion-of-human-hepatocellular-carcinoma-by-inhibiting-the-stat3-girdin-akt-activity
#18
Yang Ke, Tianhao Bao, Xuesong Wu, Haoran Tang, Yan Wang, Jiayun Ge, Bimang Fu, Xu Meng, Li Chen, Cheng Zhang, Yuqi Tan, Haotian Chen, Zhitang Guo, Fan Ni, Xuefen Lei, Zhitian Shi, Dong Wei, Lin Wang
Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27925669/biochemical-biophysical-and-cellular-techniques-to-study-the-guanine-nucleotide-exchange-factor-giv-girdin
#19
Pradipta Ghosh, Nicolas Aznar, Lee Swanson, I-Chung Lo, Inmaculada Lopez-Sanchez, Jason Ear, Cristina Rohena, Nicholas Kalogriopoulos, Linda Joosen, Ying Dunkel, Nina Sun, Peter Nguyen, Deepali Bhandari
Canonical signal transduction via heterotrimeric G proteins is spatiotemporally restricted, i.e., triggered exclusively at the plasma membrane, only by agonist activation of G protein-coupled receptors via a finite process that is terminated within a few hundred milliseconds. Recently, a rapidly emerging paradigm has revealed a noncanonical pathway for activation of heterotrimeric G proteins via the nonreceptor guanidine-nucleotide exchange factor, GIV/Girdin. Biochemical, biophysical, and functional studies evaluating this pathway have unraveled its unique properties and distinctive spatiotemporal features...
December 7, 2016: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/27864364/membrane-recruitment-of-the-non-receptor-protein-giv-girdin-g%C3%AE-interacting-vesicle-associated-protein-girdin-is-sufficient-for-activating-heterotrimeric-g-protein-signaling
#20
Kshitij Parag-Sharma, Anthony Leyme, Vincent DiGiacomo, Arthur Marivin, Stefan Broselid, Mikel Garcia-Marcos
GIV (aka Girdin) is a guanine nucleotide exchange factor that activates heterotrimeric G protein signaling downstream of RTKs and integrins, thereby serving as a platform for signaling cascade cross-talk. GIV is recruited to the cytoplasmic tail of receptors upon stimulation, but the mechanism of activation of its G protein regulatory function is not well understood. Here we used assays in humanized yeast models and G protein activity biosensors in mammalian cells to investigate the role of GIV subcellular compartmentalization in regulating its ability to promote G protein signaling...
December 30, 2016: Journal of Biological Chemistry
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