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https://www.readbyqxmd.com/read/28343945/as-human-lung-microvascular-endothelia-achieve-confluence-src-family-kinases-are-activated-and-tyrosine-phosphorylated-p120-catenin-physically-couples-neu1-sialidase-to-cd31
#1
Sang W Hyun, Anguo Liu, Zhenguo Liu, Erik P Lillehoj, Joseph A Madri, Albert B Reynolds, Simeon E Goldblum
In postconfluent human pulmonary microvascular endothelial cell (HPMEC)s, NEU1 sialidase associates with and desialylates the src family kinase (SFK) substrate, CD31, and disrupts angiogenesis. We asked whether the NEU1-CD31 interaction might be SFK-driven. We found that normalized phospho-SFK (PY416) signal is increased in postconfluent HPMECs compared to subconfluent cells and prior SFK inhibition with PP2 or SU6656 completely blocked NEU1 association with and desialylation of CD31. Prior silencing of each of the four SFKs expressed in HPMECs, as well as CD31, dramatically reduced confluence-induced SFK activation...
March 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28340249/orthodontic-strain-affects-the-hippo-pathway-effector-yap-concomitant-with-proliferation-in-human-periodontal-ligament-fibroblasts
#2
Diana Huelter-Hassler, Pascal Tomakidi, Thorsten Steinberg, Britta A Jung
Objectives: During orthodontic tooth movement (OTM), human periodontal ligament fibroblasts (hPDLFs) sense, and respond to mechanical forces. Since the molecular constituents involved in these processes are not fully elucidated, the objective of the present study was to identify further key molecules of the cellular strain response. Materials and Methods: Primary hPDLFs were strained with a static equiaxial strain of 2.5 per cent for 15 minutes, 1 hour, 6 hours, and 24 hours...
March 17, 2017: European Journal of Orthodontics
https://www.readbyqxmd.com/read/28315328/tead4-yap-interaction-regulates-tumoral-growth-by-controlling-cell-cycle-arrest-at-the-g1-phase
#3
Shin Takeuchi, Atsushi Kasamatsu, Masanobu Yamatoji, Dai Nakashima, Yosuke Endo-Sakamoto, Nao Koide, Toshikazu Takahara, Toshihiro Shimizu, Manabu Iyoda, Katsunori Ogawara, Masashi Shiiba, Hideki Tanzawa, Katsuhiro Uzawa
TEA domain transcription factor 4 (TEAD4), which has critical functions in the process of embryonic development, is expressed in various cancers. However, the important role of TEAD4 in human oral squamous cell carcinomas (OSCCs) remain unclear. Here we investigated the TEAD4 expression level and the functional mechanism in OSCC using quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. Furthermore, TEAD4 knockdown model was used to evaluate cellular proliferation, cell-cycle analysis, and the interaction between TEAD4 and Yes-associated protein (YAP) which was reported to be a transcription coactivator of cellular proliferation...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28279717/yap-and-wwtr1-new-targets-for-skin-cancer-treatment
#4
Thomas Andl, Linli Zhou, Kun Yang, Ana Luisa Kadekaro, Yuhang Zhang
The core components of the Hippo signaling pathway are a cascade of kinases that govern the phosphorylation of downstream transcriptional co-activators, namely, YES-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ). The Hippo signaling pathway is considered an important tumor-suppressor pathway, and its dysregulation has been noted in a variety of human cancers, in which YAP/WWTR1 enable cancerous cells to overcome contact inhibition, and to grow and spread uncontrollably...
March 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28259899/lats1-suppresses-proliferation-and-invasion-of-cervical-cancer
#5
Jihong Deng, Wen Zhang, Shuangyue Liu, Hongmei An, Lu Tan, Lisha Ma
Loss of large tumor suppressor kinase 1 (LATS1)Y has been implicated in numerous types of human cancer. However, its involvement in human cervical cancer remains to be elucidated. The present study aimed to investigate the clinical significance and biological characteristics of LATS1 in human cervical cancer. The present study investigated the protein expression levels of LATS1 in tissues from 80 cases of cervical cancer using immunohistochemistry and demonstrated that LATS1 was downregulated in 45% (36/80) of cervical cancers...
February 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28250241/stimulation-of-ovarian-follicle-growth-following-ampk-inhibition
#6
Xiaowei Lu, Song Guo, Yuan Cheng, Jae-Hong Kim, Yi Feng, Yun Feng
Previous studies showed that the protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and Hippo signaling-Yes associated protein (YAP) pathways play important roles in promoting follicle growth. Additionally, other studies demonstrated that 5' adenosine monophosphate-activated protein kinase (AMPK) is an upstream regulatory element of mTOR and YAP. Here, we used AMPK inhibitor (Compound C) to in vitro culture ovaries from 10-day-old mice followed by in vivo grafting into adult hosts, or to in situ treat ovaries of 3-week-old mice by intrabursal injection followed by gonadotropin stimulation...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28196718/the-neuropeptide-galanin-is-up-regulated-during-cholestasis-and-contributes-to-cholangiocyte-proliferation
#7
Matthew McMillin, Gabriel Frampton, Stephanie Grant, Sharon DeMorrow
During the course of cholestatic liver diseases, mitotically dormant cholangiocytes proliferate and subsequently acquire a neuroendocrine phenotype. Galanin is a neuroendocrine factor responsible for regulation of physiological responses, such as feeding behavior and mood, and has been implicated in the development of fatty liver disease, although its role in biliary hyperplasia is unknown. Biliary hyperplasia was induced in rats via bile duct ligation (BDL) surgery, and galanin was increased in serum and liver homogenates from BDL rats...
April 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28154141/the-nonreceptor-tyrosine-kinase-c-src-attenuates-scf-%C3%AE-trcp-e3-ligase-activity-abrogating-taz-proteasomal-degradation
#8
Matan Shanzer, Julia Adler, Inna Ricardo-Lax, Nina Reuven, Yosef Shaul
The polyomavirus middle T antigen (PyMT) oncogene activates the cellular nonreceptor tyrosine kinase c-Src and recruits the Hippo pathway effectors, Yap (yes-associated protein) and Taz (transcriptional coactivator with PDZ-binding motif), as key steps in oncogenesis. Yap and Taz are transcription coactivators shuttling from the cytoplasm to the nucleus. The Hippo pathway kinase Lats1/2 (large tumor suppressor homolog) reduces Yap/Taz nuclear localization and minimizes their cytoplasmic levels by facilitating their ubiquitination by the E3 ligase SCF(β-TrCP)...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28115535/vinculin-promotes-nuclear-localization-of-taz-to-inhibit-ecm-stiffness-dependent-differentiation-into-adipocytes
#9
Mito Kuroda, Hiroki Wada, Yasuhisa Kimura, Kazumitsu Ueda, Noriyuki Kioka
Extracellular matrix (ECM) stiffness regulates the lineage commitment of mesenchymal stem cells (MSCs). Although cells sense ECM stiffness through focal adhesion, how cells sense ECM stiffness and regulate ECM stiffness-dependent differentiation remains largely unclear. In this study, we show that cytoskeletal focal adhesion protein vinculin plays a critical role in the ECM stiffness-dependent adipocyte differentiation of MSCs. ST2 mouse MSCs differentiate into adipocytes and osteoblasts in an ECM stiffness-dependent manner...
January 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28065575/multiparametric-analysis-of-cell-shape-demonstrates-that-%C3%AE-pix-directly-couples-yap-activation-to-extracellular-matrix-adhesion
#10
Julia E Sero, Chris Bakal
Mechanical signals from the extracellular matrix (ECM) and cellular geometry regulate the nuclear translocation of transcriptional regulators such as Yes-associated protein (YAP). Elucidating how physical signals control the activity of mechanosensitive proteins poses a technical challenge, because perturbations that affect cell shape may also affect protein localization indirectly. Here, we present an approach that mitigates confounding effects of cell-shape changes, allowing us to identify direct regulators of YAP localization...
January 25, 2017: Cell Systems
https://www.readbyqxmd.com/read/28049763/the-receptor-tyrosine-kinase-axl-mediates-nuclear-translocation-of-the-epidermal-growth-factor-receptor
#11
Toni M Brand, Mari Iida, Kelsey L Corrigan, Cara M Braverman, John P Coan, Bailey G Flanigan, Andrew P Stein, Ravi Salgia, Jana Rolff, Randall J Kimple, Deric L Wheeler
The epidermal growth factor receptor (EGFR) is a therapeutic target in patients with various cancers. Unfortunately, resistance to EGFR-targeted therapeutics is common. Previous studies identified two mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Nuclear translocation of EGFR bypasses the inhibitory effects of cetuximab, and the receptor tyrosine kinase AXL mediates cetuximab resistance by maintaining EGFR activation and downstream signaling. Thus, we hypothesized that AXL mediated the nuclear translocation of EGFR in the setting of cetuximab resistance...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28028053/mrtf-potentiates-tead-yap-transcriptional-activity-causing-metastasis
#12
Tackhoon Kim, Daehee Hwang, Dahye Lee, Jeong-Hwan Kim, Seon-Young Kim, Dae-Sik Lim
Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF) play similar roles and exhibit significant crosstalk in directing transcriptional responses to chemical and physical extracellular cues. The mechanism underlying this crosstalk, however, remains unclear. Here, we show MRTF family proteins bind YAP via a conserved PPXY motif that interacts with the YAP WW domain. This interaction allows MRTF to recruit NcoA3 to the TEAD-YAP transcriptional complex and potentiate its transcriptional activity...
December 27, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28003126/emerging-role-of-hippo-signalling-in-pancreatic-biology-yap-re-expression-and-plausible-link-to-islet-cell-apoptosis-and-replication
#13
REVIEW
Anjana Sharma, Veera Ganesh Yerra, Ashutosh Kumar
Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size...
February 2017: Biochimie
https://www.readbyqxmd.com/read/28003097/hippo-signaling-in-the-liver-regulates-organ-size-cell-fate-and%C3%A2-carcinogenesis
#14
REVIEW
Sachin H Patel, Fernando D Camargo, Dean Yimlamai
The Hippo signaling pathway, also known as the Salvador-Warts-Hippo pathway, is a regulator of organ size. The pathway takes its name from the Drosophila protein kinase, Hippo (STK4/MST1 and STK3/MST2 in mammals), which, when inactivated, leads to considerable tissue overgrowth. In mammals, MST1 and MST2 negatively regulate the transcriptional co-activators yes-associated protein 1 and WW domain containing transcription regulator 1 (WWTR1/TAZ), which together regulate expression of genes that control proliferation, survival, and differentiation...
February 2017: Gastroenterology
https://www.readbyqxmd.com/read/27979972/phosphorylation-by-nlk-inhibits-yap-14-3-3-interactions-and-induces-its-nuclear-localization
#15
Sungho Moon, Wantae Kim, Soyoung Kim, Youngeun Kim, Yonghee Song, Oleksii Bilousov, Jiyoung Kim, Taebok Lee, Boksik Cha, Minseong Kim, Hanjun Kim, Vladimir L Katanaev, Eek-Hoon Jho
Hippo signaling controls organ size by regulating cell proliferation and apoptosis. Yes-associated protein (YAP) is a key downstream effector of Hippo signaling, and LATS-mediated phosphorylation of YAP at Ser127 inhibits its nuclear localization and transcriptional activity. Here, we report that Nemo-like kinase (NLK) phosphorylates YAP at Ser128 both in vitro and in vivo, which blocks interaction with 14-3-3 and enhances its nuclear localization. Depletion of NLK increases YAP phosphorylation at Ser127 and reduces YAP-mediated reporter activity...
January 2017: EMBO Reports
https://www.readbyqxmd.com/read/27901498/targeting-the-vegf-c-vegfr3-axis-suppresses-slug-mediated-cancer-metastasis-and-stemness-via-inhibition-of-kras-yap1-signaling
#16
REVIEW
Yu-Wen Yeh, Ching-Chia Cheng, Shu-Ting Yang, Chi-Feng Tseng, Ting-Yu Chang, Sin-Ying Tsai, Earl Fu, Chien-Ping Chiang, Li-Chuan Liao, Pei-Wen Tsai, Yung-Luen Yu, Jen-Liang Su
Vascular endothelial growth factor-C (VEGF-C) has been implicated in epithelial-mesenchymal transition (EMT) processes and various human cancers, including skin cancer. Skin cancer is an aggressive human malignancy with increasing incidence worldwide; however, the underlying mechanisms involved in VEGF-C-induced skin cancer stemness and metastasis remain unclear. Here, we report that VEGF-C enhances skin cancer migration, invasion and stemness through Slug up-regulation. Oncomine database analysis indicated that the KRAS/MAPK (mitogen-activated protein kinases) pathway and YAP1 (yes-associated protein 1) expression are positively correlated with metastatic skin cancer...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27869648/hippo-signaling-interactions-with-wnt-%C3%AE-catenin-and-notch-signaling-repress-liver-tumorigenesis
#17
Wantae Kim, Sanjoy Kumar Khan, Jelena Gvozdenovic-Jeremic, Youngeun Kim, Jason Dahlman, Hanjun Kim, Ogyi Park, Tohru Ishitani, Eek-Hoon Jho, Bin Gao, Yingzi Yang
Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/β-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC)...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27835600/yap1-enhances-cell-proliferation-migration-and-invasion-of-gastric-cancer-in-vitro-and-in-vivo
#18
Dan Sun, Xiaoting Li, Yingjian He, Wenhui Li, Ying Wang, Huan Wang, Shanshan Jiang, Yan Xin
Yes-associated protein 1 (YAP1) plays an important role in the development of carcinomas such as breast, colorectal, and gastric (GC) cancers, but the role of YAP1 in GC has not been investigated comprehensively. The present study strongly suggests that YAP1 and P62 were significantly up-regulated in GC specimens, compared with normal gastric mucosa. In addition, the YAP1high P62high expression was independently associated with poor prognosis in GC (hazard ratio: 1.334, 95% confidence interval: 1.045-1.704, P = 0...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27765911/integrin-%C3%AE-2%C3%AE-1-inhibits-mst1-kinase-phosphorylation-and-activates-yes-associated-protein-oncogenic-signaling-in-hepatocellular-carcinoma
#19
Kwong-Fai Wong, Angela M Liu, Wanjin Hong, Zhi Xu, John M Luk
The Hippo pathway regulates the down-stream target Yes-associated protein (YAP) to maintain organ homeostasis, which is commonly inactivated in many types of cancers. However, how cell adhesion dysregulates the Hippo pathway activating YAP oncogene in hepatocellular carcinoma (HCC) remains unclear. Our findings demonstrate that α2β1 integrin (but not other β1 integrins) expressed in HCC cells, after binding to collagen extracellular matrix, could inhibit MST1 kinase phosphorylation and activate YAP pro-oncogenic activities...
October 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27756880/lyn-expression-predicts-the-response-to-dasatinib-in-a-subpopulation-of-lung-adenocarcinoma-patients
#20
Yu Jin Kim, Sungyoul Hong, Minjung Sung, Min Jeong Park, Kyungsoo Jung, Ka-Won Noh, Doo-Yi Oh, Mi-Sook Lee, Ensel Oh, Young Kee Shin, Yoon-La Choi
Therapies targeting SRC family kinases (SFKs) have shown efficacy in treating non-small cell lung cancer (NSCLC). However, recent clinical trials have found that the SFK inhibitor dasatinib is ineffective in some patient cohorts. Regardless, dasatinib treatment may benefit some NSCLC patient subgroups. Here, we investigated whether expression of LYN, a member of the SFK family, is associated with patient survival, the efficacy of dasatinib, and/or NSCLC cell viability. LYN expression was associated with poor overall survival in a multivariate analysis, and this association was strongest in non-smoker female patients with adenocarcinoma (ADC)...
October 14, 2016: Oncotarget
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