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Yes kinase

Takaaki Sugihara, Nathan W Werneburg, Matthew C Hernandez, Lin Yang, Ayano Kabashima, Petra Hirsova, Lavanya Yohanathan, Carlos Sosa, Mark Joseph Truty, George Vasmatzis, Gregory J Gores, Rory L Smoot
The hippo pathway effector, Yes-associated protein (YAP) is a transcriptional co-activator implicated in cholangiocarcinoma (CCA) pathogenesis. YAP is known to be regulated by a serine/threonine kinase relay module (MST1/2 - LATS1/2) culminating in phosphorylation of YAP at Serine 127 (S127) and cytoplasmic sequestration. However, YAP also undergoes tyrosine phosphorylation, and the role of tyrosine phosphorylation in YAP regulation remains unclear. Herein, YAP regulation by tyrosine phosphorylation was examined in human and mouse CCA cells, as well as patient-derived xenograft (PDX) models...
June 14, 2018: Molecular Cancer Research: MCR
Chengyong Lei, Shidong Lv, Hongyi Wang, Chuan Liu, Qiliang Zhai, Shanci Wang, Guixing Cai, Dingheng Lu, Zhen Sun, Qiang Wei
The role of leukemia inhibitory factor receptor (LIFR), which is important in the signal transduction of the interleukin-6 cytokine family, is still undefined in clear cell renal cell carcinoma (ccRCC). Thus, we examined the function and mechanism of LIFR in ccRCC. Low LIFR expression correlated with a poor prognosis and an aggressive tumor phenotype. Moreover, integrated LIFR DNA and mRNA analysis revealed that promoter methylation and copy number variation contributed to the reduced LIFR expression. LIFR knockdown increased 786-O and Caki-2 cell invasion and migration...
June 14, 2018: DNA and Cell Biology
Qingping Guo, Jiale Wang, Zeyu Cao, Yongchang Tang, Chao Feng, Feizhou Huang
Despite advances in surgery and chemotherapy, the prognosis of patients with hepatocellular carcinoma (HCC) remains poor. In the present study, the role of S100A1 in the progression of HCC was investigated. Immunohistochemical staining was used to measure the expression of S100A1 in HCC tissues. S100A1 was knocked down by siRNA. A battery of experiments was used to evaluate the biology functions of S100A1. It was found that S100A1 was upregulated in HCC tissues, and its upregulation was associated with a large tumor size, low differentiation and shorter survival time...
June 5, 2018: International Journal of Oncology
Shiyuan Huang, Xiaona Wang, Xinmei Wu, Jiale Yu, JinJing Li, Xiaoyuan Huang, Chunfang Zhu, Hongshan Ge
Yes-associated protein (Yap) was the core transcriptional co-activator in the downstream Hippo pathway that regulated cell proliferation and tissue growth. However, its role in the regulation of myoblast differentiation remains unclear. Regulation of mitochondrial networks by dynamin-related protein 1 (Drp1) and mitofusion 2 (Mfn2) is crucial for the activation of myoblast differentiation. In the present study, we investigated the interplay between the Hippo-Yap pathway and protein contents of Mfn2 and Drp1 during myoblast differentiation...
June 13, 2018: American Journal of Physiology. Cell Physiology
Ying Shi, Xue Lv, Yanan Liu, Bochuan Li, Mingming Liu, Meng Yan, Yajin Liu, Qi Li, Xuejiao Zhang, Shuang He, Mason Zhu, Jinlong He, Yan Zhu, Yi Zhu, Ding Ai
Endothelial progenitor cell (EPC) dysfunction contributes to diabetes-induced delay in endothelium repair after vessel injury, prominently associated with diabetic cardiovascular complications such as neointima formation. ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux to HDL, which may favorably affect EPC function. However, whether ABCG1 improves EPC function, especially in diabetes, remains unknown. Here we investigated the role of ABCG1 in EPCs by using Tie2-mediated ABCG1 transgenic (Tie2- ABCG1Tg ) mice...
June 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
JingJing Zhang, Yi Lu
While biocomputing is recognized to provide intelligent solution to complex biosensing projects, it remains challenging to transform biomolecular logic gates into a convenient, portable, resettable and quantitative sensing system for point-of-care (POC) diagnostics in a low-resource setting. To overcome these limitations, we herein report the first design and demonstration of biocomputing on personal glucose meters (PGM) by utilizing glucose and nicotinamide adenine dinucleotide as signal outputs, DNAzyme and protein enzymes as building blocks and demonstrating a general platform for installing logic-gate responses (YES, NOT, INHIBIT and OR) to a variety of biological species, such as cations (sodium), anions (citrate), organic metabolites (ADP, ATP) and enzymes (pyruvate kinase, alkaline phosphatase, alcohol dehydrogenases)...
June 12, 2018: Angewandte Chemie
Yusuke Oku, Naoyuki Nishiya, Shuhei Sugiyama, Haruka Sato, Yoshimasa Uehara
BACKGROUND: Transcriptional co-activators YES-associated protein (YAP) and transcriptional coactivator with PDZ-motif (TAZ) stimulate the expression of cell cycle-related genes to permit for tumour cell growth. MLN8237 is a potent aurora-A kinase inhibitor; however, patients responding to MLN8237 are limited. Therefore, rational combination therapy could enhance their response. MATERIALS AND METHODS: YAP and TAZ were depleted using siRNA and then treated with MLN8237 in YAP/TAZ-dependent OVCAR-8 and MDA-MB-231 cell lines...
June 2018: Anticancer Research
Peter D Jones, Michael A Kaiser, Maryam Ghaderi Najafabadi, Simon Koplev, Yuqi Zhao, Gillian Douglas, Theodosios Kyriakou, Sarah Andrews, Rathinasabapathy Rajmohan, Hugh Watkins, Keith M Channon, Shu Ye, Xia Yang, Johan L M Björkegren, Nilesh J Samani, Tom R Webb
OBJECTIVE: A large number of genetic loci have been associated with risk of coronary artery disease (CAD) through genome-wide association studies, however, for most loci the underlying biological mechanism is unknown. Determining the molecular pathways and cellular processes affected by these loci will provide new insights into CAD pathophysiology and may lead to new therapies. The CAD-associated variants at 10p11.23 fall in JCAD , which encodes an endothelial junction protein, however, its molecular function in endothelial cells is not known...
May 24, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Xiaoling Liu, Xinyu Long, Weiwei Liu, Yeli Zhao, Toshihiko Hayashi, Masayuki Yamato, Kazunori Mizuno, Hitomi Fujisaki, Shunji Hattori, Shin-Ichi Tashiro, Takaaki Ogura, Yuji Atsuzawa, Takashi Ikejima
In organ fibrosis, mechanical stress and transforming growth factor beta-1 (TGF-β1) promote differentiation into myofibroblast from mesenchymal cells, leading to extracellular matrix (ECM) remodeling or active synthesis, deposition or degradation of ECM components. A major component of ECM, type I collagen (col I) triple helical molecules assemble into fibrils or are denatured to gelatin without triple-helicity in remodeling. However, whether changes of ECM components in remodeling have influence on mesenchymal cell differentiation remains elusive...
July 2018: Biochimie
Cyril Thouverey, Serge Ferrari, Joseph Caverzasio
Mice deficient in the non-receptor tyrosine kinase Src exhibit high bone mass due to impaired bone resorption and increased bone formation. Although several Src family kinase inhibitors inhibit bone resorption in vivo, they display variable effects on bone formation. SU6656 is a selective Src family kinase inhibitor with weaker activity towards the non-receptor tyrosine kinase Abl and receptor tyrosine kinases which are required for appropriate osteoblast proliferation, differentiation and function. Therefore, we sought to determine whether SU6656 could increase bone mass by inhibiting bone resorption and by stimulating bone formation, and to explore its mechanisms of action...
May 8, 2018: Bone
Yusuke Takehara, Toshiko Yamochi, Tasuku Nagumo, Tomonari Cho, Fumihiko Urushibara, Kohei Ono, Tomonori Fujii, Naoko Okamoto, Yosuke Sasaki, Sakiko Tazawa, Mayumi Honma, Tomoko Norose, Eisuke Shiozawa, Genshu Tate, Masafumi Takimoto
Gene mutations are involved in the development of malignant mesothelioma. Important mutations have been identified in the genes for cyclin-dependent kinase inhibitor 2A (p16) alternative reading frame, breast cancer-associated protein 1 ( BAP1 ) and neurofibromatosis type 2 ( NF2 ). Previously, the utility of detecting the loss of BAP1 by immunohistochemistry (IHC) and p16-deletion by fluorescence in situ hybridization has been identified in several studies. However, NF2 -associated examinations have not been performed...
May 2018: Oncology Letters
Shuai Liu, Peng Chen, Yan-Wei Liu, Xue-Nan Gu, Xiao-Guang Qiu, Bo Li
Background: The role of postradiation systemic therapy in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) was controversial. Thus, we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) and graded prognostic assessment (GPA) in identifying population who may benefit from postradiation systemic therapy. Methods: The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively...
May 20, 2018: Chinese Medical Journal
Yao Xiao, Wei-Wei Deng, Lei-Lei Yang, Hao Li, Guang-Tao Yu, Wen-Feng Zhang, Zhi-Jun Sun
AIM: p21-activated kinase 2 (PAK2) is overexpressed in several tumors but the expression of PAK2 in oral squamous cell carcinomas (OSCCs) remains unclear. MATERIALS & METHODS: Immunohistochemistry was performed on human tissue microarrays containing 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa. RESULTS: PAK2 expression was increased in primary OSCC compared with normal mucosa and significantly increased in primary OSCC grade III compared with grade I, but independent of overall survival rate...
May 1, 2018: Future Oncology
Suman Dalal, Barbara Connelly, Mahipal Singh, Krishna Singh
METHODS AND RESULTS: Treatment of adult rat ventricular myocytes (ARVMs) with β-AR agonist (isoproterenol) for 15 min increased phosphorylation (serine-518) and sumoylation of NF2. Co-immunoprecipitation assay confirmed β-AR-stimulated sumoylation of NF2. β-AR stimulation enhanced nuclear translocation of phosphorylated and sumoylated NF2. Specific inhibition of β1-AR and protein kinase A (PKA) decreased β-AR-stimulated increase in NF2 post-translational modifications, while inhibition of β2-AR had no effect...
2018: PloS One
Somi Park, Museog Choe, Hancheol Yeo, Hojae Han, Joongsun Kim, Woocheol Chang, Seungpil Yun, Hojin Lee, Minyoung Lee
Unlike mature cardiomyocytes, human pluripotent stem cell-derived cardiomyocytes exhibit higher proliferative capacity; however, the underlying mechanisms involved are yet to be elucidated. Here, we revealed that the Yes-associated protein (YAP) plays a critical role in regulating cell proliferation in association with epidermal growth factor receptor (EGFR) in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). Our results show that low-density culture significantly promotes the proliferation of hESC-CMs via YAP...
April 25, 2018: Journal of Cellular Physiology
Weicheng Zhang, Jingyuan Shen, Fengming Gu, Ying Zhang, Wenjuan Wu, Jiachun Weng, Yuexia Liao, Zijing Deng, Qing Yuan, Lu Zheng, Yu Zhang, Weigan Shen
Accumulating evidence implicates monopolar spindle-one-binder protein (MOB)2 as an inhibitor of nuclear-Dbf2-related kinase (NDR) by competing with MOB1 for interaction with NDR1/2. NDR/large tumor suppressor (LATS) kinases may function similarly to yes-associated protein (YAP) kinases and be considered as members of the Hippo core cassette. MOB2 appears to serve roles in cell survival, cell cycle progression, responses to DNA damage and cell motility. However, the underlying mechanisms involved remain unclarified...
April 2018: Oncology Letters
Yulei Zhao, Tess Montminy, Taha Azad, Elizabeth Lightbody, Yawei Hao, Sandip SenGupta, Eric Asselin, Christopher Nicol, Xiaolong Yang
Breast cancer is a leading cause of death in women worldwide. Active mutations of PI3K catalytic subunit PIK3CA (e.g., H1047R) and amplification of its homolog PIK3CB are observed in a large number of breast cancers. In recent years, aberrant activation of Transcriptional coactivator with PDZ binding motif (TAZ) and its paralog Yes-associated protein (YAP) have also been found to be important for breast cancer development and progression. However, whether PI3K interacts with YAP/TAZ during mammary tumorigenesis is unknown...
March 15, 2018: Molecular Cancer Research: MCR
Carole Sourbier, Pei-Jyun Liao, Christopher J Ricketts, Darmood Wei, Youfeng Yang, Sarah M Baranes, Benjamin K Gibbs, Lernik Ohanjanian, L Spencer Krane, Bradley T Scroggins, J Keith Killian, Ming-Hui Wei, Toshiki Kijima, Paul S Meltzer, Deborah E Citrin, Len Neckers, Cathy D Vocke, W Marston Linehan
Papillary renal cell carcinomas (PRCC) are a histologically and genetically heterogeneous group of tumors that represent 15-20% of all kidney neoplasms and may require diverse therapeutic approaches. Alteration of the NF2 tumor suppressor gene, encoding a key regulator of the Hippo signaling pathway, is observed in 22.5% of PRCC. The Hippo signaling pathway controls cell proliferation by regulating the transcriptional activity of Yes-Associated Protein, YAP1. Loss of NF2 results in aberrant YAP1 activation...
February 13, 2018: Oncotarget
Hiroki Goto, Miki Nishio, Yoko To, Tatsuya Oishi, Yosuke Miyachi, Tomohiko Maehama, Hiroshi Nishina, Haruhiko Akiyama, Tak Wah Mak, Yuma Makii, Taku Saito, Akihiro Yasoda, Noriyuki Tsumaki, Akira Suzuki
Hippo signaling is modulated in response to cell density, external mechanical forces, and rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and influence Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown...
March 16, 2018: Development
Apoorva Verma, Fan Jing-Song, Megan L Finch-Edmondson, Adrian Velazquez-Campoy, Shanker Balasegaran, Marius Sudol, Jayaraman Sivaraman
YES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1...
January 30, 2018: Oncotarget
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