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https://www.readbyqxmd.com/read/29552181/monopolar-spindle-one-binder-protein-2-regulates-the-activity-of-large-tumor-suppressor-yes-associated-protein-to-inhibit-the-motility-of-smmc-7721-hepatocellular-carcinoma-cells
#1
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
https://www.readbyqxmd.com/read/29545474/pi3k-regulates-yap-taz-in-mammary-tumorigenesis-through-multiple-signaling-pathways
#2
Yulei Zhao, Tess Montminy, Taha Azad, Elizabeth Lightbody, Yawei Hao, Sandip SenGupta, Eric Asselin, Christopher Jb Nicol, Xiaolong Yang
Breast cancer (BC) 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 occur in many BC cases. In recent years, activation of the Transcriptional coactivator with PDZ binding motif (TAZ) and its paralog Yes-associated protein (YAP) have been found to be important for BC development and progression. However, there is no evidence that PI3K interacts with YAP/TAZ in mammary tumorigenesis. Using a systematic gain-of-function screen for kinases involved in mammary tumorigenesis, PIK3CB was identified as a transformation inducing kinase...
March 15, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29535838/targeting-loss-of-the-hippo-signaling-pathway-in-nf2-deficient-papillary-kidney-cancers
#3
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
https://www.readbyqxmd.com/read/29511023/loss-of-mob1a-b-in-mice-results-in-chondrodysplasia-due-to-yap1-taz-teads-dependent-repression-of-sox9
#4
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, or rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and have important effects on 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 6, 2018: Development
https://www.readbyqxmd.com/read/29487715/biophysical-studies-and-nmr-structure-of-yap2-ww-domain-lats1-ppxy-motif-complexes-reveal-the-basis-of-their-interaction
#5
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
https://www.readbyqxmd.com/read/29487002/overexpression-of-yap1-in-egfr-mutant-lung-adenocarcinoma-prior-to-tyrosine-kinase-inhibitor-therapy-is-associated-with-poor-survival
#6
Soon Auck Hong, Si-Hyong Jang, Mee-Hye Oh, Sung Joon Kim, Jin-Hyung Kang, Sook-Hee Hong
EGFR tyrosine kinase inhibitor (EGFR TKI) is approved as first-line treatment for advanced-stage EGFR mutant lung adenocarcinoma (LADC). Yes-associated protein 1 (YAP1), a main effector of the Hippo pathway, is associated with adverse prognosis and disruption of EGFR TKI modulation of non-small cell lung cancer. In this study, we demonstrated a prognostic role of YAP1 in EGFR mutant LADC and efficacy of EGFR TKI therapy. A total of 63 patients, including 41 with paired lung cancer specimens before and after EGFR TKI therapy and 22 with non-paired lung cancer specimens prior to EGFR TKI, were enrolled for examination...
February 3, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29473166/capillary-morphogenesis-protein-2-is-a-novel-prognostic-biomarker-and-plays-oncogenic-roles-in-glioma
#7
Juan Tan, Mei Liu, Jun-Ying Zhang, Yue-Liang Yao, Yan-Xia Wang, Yong Lin, Kang Song, Jiao Tan, Jin-Rong Wu, You-Hong Cui, Yan Wang, Xiu-Wu Bian
Capillary morphogenesis protein 2 (CMG2) was originally identified through its participation in capillary morphogenesis, and subsequently identified as the second receptor for anthrax toxin (ANTXR2). Although tumor-associated functions of CMG2 have also been reported, the clinical significance and functional mechanism of CMG2 in glioma remain to be elucidated. We assessed the clinicopathological relevance of CMG2 in a cohort of 48 glioma patients as well as through public glioma databases, and explored the function of CMG2 using glioblastoma (GBM) models in vitro and in vivo...
February 23, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29457552/reciprocal-regulation-of-yap-taz-by-the-hippo-pathway-and-the-small-gtpase-pathway
#8
Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae
Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#9
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29416763/dysregulation-of-yap-by-the-hippo-pathway-is-involved-in-intervertebral-disc-degeneration-cell-contact-inhibition-and-cell-senescence
#10
Cong Zhang, Feng Wang, Zhiyang Xie, Lu Chen, Arjun Sinkemani, Haomin Yu, Kun Wang, Lu Mao, Xiaotao Wu
The Hippo pathway plays important roles in wound healing, tissue repair and regeneration, and in the treatment of degenerative diseases, by regulating cell proliferation and apoptosis in mammals. Intervertebral disc degeneration (IDD) is one of the major causes of low back pain, a widespread issue associated with a heavy economic burden. However, the mechanism underlying how the Hippo pathway regulates IDD is not well understood. Here, we demonstrate that the Hippo pathway is involved in natural IDD. Activation and dephosphorylation of yes-associated protein (YAP) were observed in younger rat discs, and decreased gradually with age...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29403552/downregulation-of-yap-inhibits-proliferation-and-induces-apoptosis-in-eca-109-cells
#11
Mu Cui, Zhen Li
A previous study reported that Yes-associated protein (YAP) gene was overexpressed in esophageal squamous cell carcinoma (ESCC); however, the exact role of YAP in ESCC remains largely unclear. The present study aimed to investigate the effects of YAP inhibition on ESCC. In order to investigate the exact role of YAP in ESCC cells, a stable YAP low-expression ESCC cell line was established using YAP-small interfering RNA. MTT assay was performed to examine the cell proliferation ability, while flow cytometry were used to detect the cell apoptosis and cell cycle distribution...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29400695/claudin-18-mediated-yap-activity-regulates-lung-stem-and-progenitor-cell-homeostasis-and-tumorigenesis
#12
Beiyun Zhou, Per Flodby, Jiao Luo, Dan R Castillo, Yixin Liu, Fa-Xing Yu, Alicia McConnell, Bino Varghese, Guanglei Li, Nyam-Osor Chimge, Mitsuhiro Sunohara, Michael N Koss, Wafaa Elatre, Peter Conti, Janice M Liebler, Chenchen Yang, Crystal N Marconett, Ite A Laird-Offringa, Parviz Minoo, Kunliang Guan, Barry R Stripp, Edward D Crandall, Zea Borok
Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice...
February 5, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29366445/clinical-implications-of-the-hippo-yap-pathway-in-multiple-cancer-contexts
#13
Han-Byul Kim, Seung-Jae Myung
The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy...
January 25, 2018: BMB Reports
https://www.readbyqxmd.com/read/29344656/liraglutide-suppresses-proliferation-and-induces-adipogenic-differentiation-of-3t3-l1-cells-via-the-hippo-yap-signaling-pathway
#14
Yongmei Li, Jianying Du, Endong Zhu, Juanjuan Zhang, Jie Han, Wei Zhao, Bei Sun, Derun Tian
Liraglutide, as a glucagon-like peptide‑1 analogue, is used to treat type 2 diabetes mellitus and obesity. Previous findings have demonstrated the effects of liraglutide on adipogenesis; however, the underlying mechanism involved in this process remains to be elucidated. In the present study, to certify the effect of liraglutide on adipogenesis and explore the possible underlying mechanism involved in this process, preadipocyte 3T3‑L1 cells were cultured in adipocyte‑inducing medium and treated with liraglutide...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29321482/enhanced-yap-expression-leads-to-egfr-tki-resistance-in-lung-adenocarcinomas
#15
Ting-Fang Lee, Yu-Chi Tseng, Phung Anh Nguyen, Yu-Chuan Li, Chao-Chi Ho, Cheng-Wen Wu
Epidermal growth factor receptor (EGFR) mutation is prevalently expressed in lung adenocarcinoma cases and acts as one of the major driving oncogenes. EGFR tyrosine kinase inhibitors (TKIs) have been used in patients with EGFR-mutant as an effective targeted therapy in lung adenocarcinoma, but drug resistance and tumor recurrence inevitably occurs. Recently, Yes-associate protein (YAP) has been reported to promote multiple cancer cell properties, such as promoting cell proliferation, epithelial-mesenchymal transition and drug resistance...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316729/wnt-rspo-and-hippo-signalling-in-the-intestine-and-intestinal-stem-cells
#16
REVIEW
Vitezslav Kriz, Vladimir Korinek
In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling...
January 8, 2018: Genes
https://www.readbyqxmd.com/read/29228123/role-of-yes-associated-protein-1-angiomotin-and-mitogen-activated-kinase-kinase-1-2-in-development-of-the-bovine-blastocyst
#17
Verónica M Negrón-Pérez, Peter J Hansen
The morula-stage embryo is transformed into a blastocyst composed of epiblast, hypoblast, and trophectoderm (TE) through mechanisms that, in the mouse, involve the Hippo signaling and mitogen-activated kinase (MAPK) pathways. Using the cow as an additional model, we tested the hypotheses that TE and hypoblast differentiation were regulated by the Hippo pathway regulators, yes-associated protein 1 (YAP1) and angiomotin (AMOT), and MAPK kinase 1/2 (MAPK1/2). The presence of YAP1 and CDX2 in the nucleus and cytoplasm of MII oocytes and embryos was evaluated by immunofluorescence labeling...
February 1, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29206651/novel-therapeutic-strategies-and-targets-in-advanced-uveal-melanoma
#18
Vivian Chua, Andrew E Aplin
PURPOSE OF REVIEW: Currently, there are no U.S. Food and Drug Administration-approved or effective treatment options for advanced-stage uveal melanoma. In this article, we focus on therapeutic targets in pathways/mechanisms associated with common mutations in uveal melanoma. We review the challenges associated with targeting of these pathways and novel treatment strategies. RECENT FINDINGS: Common mutations that promote uveal melanoma initiation and progression include alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1-associated protein 1 (BAP1)...
March 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29184109/activation-of-erk-in-ileal-epithelial-cells-engaged-in-ischemic-injury-repair
#19
Haruna Takeda, Etsuko Kiyokawa
Intestinal epithelial cells function as a barrier to protect our body from various agents; therefore, any damage to these cells must be immediately repaired. Several in vivo and vitro studies have shown the involvement of Erk (extracellular signal-regulated kinase) in the regeneration process; however, the spatial regulation of Erk related to tissue morphology has not been well documented. Using two-photon microscopy and mice carrying a Förster resonance energy transfer-based biosensor, we here monitored the Erk activity in the ileal epithelial cells of living mice...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29175418/src-family-kinase-tyrosine-phosphorylates-toll-like-receptor-4-to-dissociate-myd88-and-mal-tirap-suppressing-lps-induced-inflammatory-responses
#20
Jonathon Mitchell, Su Jin Kim, Alexandra Seelmann, Brendan Veit, Brooke Shepard, Eunok Im, Sang Hoon Rhee
Src family kinases (SFKs) are a family of protein tyrosine kinases containing nine members: Src, Lyn, Fgr, Hck, Lck, Fyn, Blk, Yes, and Ylk. Although SFK activation is a major immediate signaling event in LPS/Toll-like receptor 4 (TLR4) signaling, its precise role has remained elusive due to various contradictory results obtained from a certain SFK member-deficient mice or cells. The observed inconsistencies may be due to the compensation or redundancy by other SFKs upon a SFK deficiency. The chemical rescuing approach was suggested to induce temporal and precise SFK activation in living cells, thereby limiting the chance of cellular adaption to a SFK-deficient condition...
January 2018: Biochemical Pharmacology
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