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Cellular Signalling

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https://www.readbyqxmd.com/read/28093267/interleukin-6-induces-cell-proliferation-of-clear-cell-renal-cell-carcinoma-by-suppressing-hepacam-via-the-stat3-dependent-up-regulation-of-dnmt1-or-dnmt3b
#1
Zhen Quan, Yunfeng He, Chunli Luo, Yang Xia, Yan Zhao, Nanjing Liu, Xiaohou Wu
Interleukin 6 (IL-6), a tumor promoting cytokine, has been largely implicated in the development of renal cell carcinoma (RCC). Hepatocyte cell adhesion molecule (hepaCAM) is a novel tumor suppressor, which is lost or down-regulated in many cancer types including RCC. In the present study, we intensively investigated the connection between IL-6 and hepaCAM in RCC. Our analysis of RCC tissues, adjacent tissues and paired serum samples from RCC patients revealed that IL-6 was elevated in patient serum and RCC tissue, whereas hepaCAM was completely lost or significantly down-regulated...
January 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28089905/nudix-type-motif-2-contributes-to-cancer-proliferation-through-the-regulation-of-rag-gtpase-mediated-mammalian-target-of-rapamycin-complex-1-localization
#2
Ohman Kwon, Dongoh Kwak, Sang Hoon Ha, Hyeona Jeon, Mangeun Park, Yeonho Chang, Pann-Ghill Suh, Sung Ho Ryu
Lysosomal localization of mammalian target of rapamycin complex 1 (mTORC1) is a critical step for activation of the molecule. Rag GTPases are essential for this translocation. Here, we demonstrate that Nudix-type motif 2 (NUDT2) is a novel positive regulator of mTORC1 activation. Activation of mTORC1 is impaired in NUDT2-silenced cells. Mechanistically, NUDT2 binds to Rag GTPase and controls mTORC1 translocation to the lysosomal membrane. Furthermore, NUDT2-dependent mTORC1 regulation is critical for proliferation of breast cancer cells, as NUDT2-silenced cells arrest in G0/G1 phases...
January 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28088389/nalfurafine-is-a-g-protein-biased-agonist-having-significantly-greater-bias-at-the-human-than-rodent-form-of-the-kappa-opioid-receptor
#3
Selena S Schattauer, Jamie R Kuhar, Allisa Song, Charles Chavkin
Nalfurafine is a moderately selective kappa opioid receptor (KOR) analgesic with low incidence of dysphoric side effects in clinical development for the treatment of uremic pruritis. The basis for its reduced dysphoric effect compared to other KOR agonists is not clear, but prior studies suggest that the aversive properties of KOR agonists require p38α MAPK activation through an arrestin-dependent mechanism. To determine whether nalfurafine is a functionally selective KOR agonist, we measured its potency to activate the G protein-dependent early phase of Extracellular Signal-Regulated Kinase (ERK1/2) phosphorylation and the arrestin-dependent late phase of p38 MAPK signaling...
January 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28089769/nuclear-translocation-of-stat3-and-nf-%C3%AE%C2%BAb-are-independent-of-each-other-but-nf-%C3%AE%C2%BAb-supports-expression-and-activation-of-stat3
#4
Antons Martincuks, Katarzyna Andryka, Andrea Küster, Hildegard Schmitz-Van de Leur, Michal Komorowski, Gerhard Müller-Newen
NF-κB and STAT3 are essential transcription factors in immunity and act at the interface of the transition from chronic inflammation to cancer. Different functional crosstalks between NF-κB and STAT3 have been recently described arguing for a direct interaction of both proteins. During a systematic analysis of NF-κB/STAT3 crosstalk we observed that appearance of the subcellular distribution of NF-κB and STAT3 in immunofluorescence heavily depends on the fixation procedure. Therefore, we established an optimized fixation protocol for the reliable simultaneous analysis of the subcellular distributions of both transcription factors...
January 9, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28077325/role-of-14-3-3-sigma-in-over-expression-of-p-gp-by-rifampin-and-paclitaxel-stimulation-through-interaction-with-pxr
#5
So Won Kim, Md Hasanuzzaman, Munju Cho, Nam Hyun Kim, Hye-Young Choi, Jung Woo Han, Hyun June Park, Ji Won Oh, Jae-Gook Shin
In this study, we presented the role of 14-3-3σ to activate CK2-Hsp90β-PXR-MDR1 pathway on rifampin and paclitaxel treated LS174T cells and in vivo LS174T cell-xenografted nude mouse model. Following several in vitro and in vivo experiments, rifampin and paclitaxel were found to be stimulated the CK2-Hsp90β-PXR-MDR1 pathway. Of the proteins in this pathway, Pregnane X receptor (PXR) is a representative transcription factor of multidrug resistance protein 1 (MDR1). We constructed FLAG-PXR-LS174T stable cell lines and discovered 22 proteins that interacted with PXR on rifampin treatment...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28077324/grk2-as-negative-modulator-of-no-bioavailability-implications-for-cardiovascular-disease
#6
REVIEW
Alessandro Cannavo, Walter J Koch
Nitric oxide (NO), initially identified as endothelium-derived relaxing factor (EDRF), is a gaso-transmitter with important regulatory roles in the cardiovascular, nervous and immune systems. In the former, this diatomic molecule and free radical gas controls vascular tone and cardiac mechanics, among others. In the cardiovascular system, it is now understood that β-adrenergic receptor (βAR) activation is a key modulator of NO generation. Therefore, it is not surprising that the up-regulation of G protein-coupled receptor kinases (GRKs), in particular GRK2, that restrains βAR activity contributes to impaired cardiovascular functions via alteration of NO bioavailability...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28077323/high-glucose-down-regulates-microrna-181a-5p-to-increase-pro-fibrotic-gene-expression-by-targeting-early-growth-response-factor-1-in-hk-2-cells
#7
Ping Xu, Mei-Ping Guan, Jian-Gang Bi, Dan Wang, Zong-Ji Zheng, Yao-Ming Xue
Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial effect of early growth response factor 1 (Egr1) on renal fibrosis in DN, but the underlying mechanisms are not entirely clear. Here, we explored the aggravating role of Egr1 and identified microRNA-181a-5p (miR-181a-5p) as an upstream regulator of Egr1 in TIF of DN. We demonstrated that overexpression of Egr1 enhanced, whereas small interfering RNA targeting Egr1 decreased the expressions of transforming growth factor β1 (TGF-β1) and fibrosis-related genes including fibronectin and collagen I in human proximal tubule cell line (HK-2) cells...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28077322/a-protein-kinase-a-ezrin-complex-regulates-connexin-43-gap-junction-communication-in-liver-epithelial-cells
#8
Aleksandra Dukic, Linda Hofstad Haugen, Guillaume Pidoux, Edward Leithe, Oddmund Bakke, Kjetil Taskén
Communication between adjacent cells can occur via gap junctions (GJ) composed of connexin (Cx) hexamers that allow passage of small molecules. One of the most widely and highly expressed Cxs in human tissues is Cx43, shown to be regulated through phosphorylation by several kinases including PKA. Ezrin is a membrane associated protein that can serve as an A kinase anchoring protein (AKAP) and hold an anchored pool of PKA. Here, we used the liver epithelial cell line IAR20, which expresses Cx43 as the predominant GJ protein, to test the hypothesis that Ezrin may associate with Cx43 in cell types that form stable GJs and serve as an AKAP...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28069442/novel-signaling-of-dynorphin-at-%C3%AE%C2%BA-opioid-receptor-bradykinin-b2-receptor-heterodimers
#9
Bingyuan Ji, Haiqing Liu, Rumin Zhang, Yunlu Jiang, Chunmei Wang, Sheng Li, Jing Chen, Bo Bai
The κ-opioid receptor (KOR) and bradykinin B2 receptor (B2R) are involved in a variety of important physiological processes and share many similar characteristics in terms of their distribution and functions in the nervous system. We first demonstrated the endogenous expression of KOR and B2R in human SH-SY5Y cells and their co-localization on the membrane of human embryonic kidney 293 (HEK293) cells. Bioluminescence and fluorescence resonance energy transfer and the proximity ligation assay were exploited to demonstrate the formation of functional KOR and B2R heteromers in transfected cells...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28069441/transcription-of-hotair-is-regulated-by-rhoc-mrtf-a-srf-signaling-pathway-in-human-breast-cancer-cells
#10
Hongpeng He, Zhaoqiang Wei, Fu Du, Chao Meng, Deliang Zheng, Yongwei Lai, Hailin Yao, Hao Zhou, Nan Wang, Xue-Gang Luo, Wenjian Ma, Tong-Cun Zhang
HOTAIR is a long non-coding RNA highly expressed in cancer tissues and is a negative prognostic factor, whereas the mechanism by which HOTAIR expression is upregulated in cancers remains elusive. In the present study, the regulation of HOTAIR transcription was investigated in breast cancer cells MCF7 and T47D. We found that, when the RhoC-ROCK signaling was disturbed by specific siRNAs or chemical inhibitors, the expression of HOTAIR would be down-regulated. Further, MRTF-A and SRF were found to affect HOTAIR expression...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28069443/the-cyclic-amp-phosphodiesterase-4d5-pde4d5-receptor-for-activated-c-kinase-1-rack1-signalling-complex-as-a-sensor-of-the-extracellular-nano-environment
#11
REVIEW
Stephen J Yarwood, Euan Parnell, Rebecca J Bird
The cyclic AMP and protein kinase C (PKC) signalling pathways regulate a wide range of cellular processes that require tight control, including cell proliferation and differentiation, metabolism and inflammation. The identification of a protein complex formed by receptor for activated C kinase 1 (RACK1), a scaffold protein for protein kinase C (PKC), and the cyclic AMP-specific phosphodiesterase, PDE4D5, demonstrates a potential mechanism for crosstalk between these two signalling routes. Indeed, RACK1-bound PDE4D5 is activated by PKCα, providing a route through which the PKC pathway can control cellular cyclic AMP levels...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28069440/inter-and-intra-cellular-mechanism-of-nf-kb-dependent-survival-advantage-and-clonal-expansion-of-radio-resistant-cancer-cells
#12
Hui Yu, Natarajan Aravindan, Ji Xu, Mohan Natarajan
Understanding the underlying mechanism by which cancer cells acquire resistance to radiation and favorably selected for its clonal expansion will provide molecular insight into tumor recurrence at the treatment site. In the present study, we investigated the molecular mechanisms prompted in MCF-7 breast cancer cells in response to clinical radiation and the associated coordination of intra- and inter-cellular signaling that orchestrate radio-resistance and tumor relapse/recurrence. Our findings showed that 2 or 10Gy of (137)Cs γ-rays at a dose rate of 1...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28069439/hakai-an-e3-ligase-for-e-cadherin-stabilizes-%C3%AE-catenin-through-src-kinase
#13
Hridaya Shrestha, Taeyong Ryu, Young-Woo Seo, So-Yeon Park, Yongfeng He, Weiye Dai, Eunsook Park, Shishli Simkhada, Hangun Kim, Keesook Lee, Kwonseop Kim
Hakai ubiquitinates and induces endocytosis of the E-cadherin complex; thus, modulating cell adhesion and regulating development of the epithelial-mesenchymal transition of metastasis. Our previous published data show that δ-catenin promotes E-cadherin processing and thereby activates β-catenin-mediated oncogenic signals. Although several published data show the interactions between δ-catenin and E-cadherin and between Hakai and E-cadherin separately, we found no published report on the relationship between δ-catenin and Hakai...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28069438/ribosomal-protein-pno40-mediates-nucleolar-sequestration-of-sr-family-splicing-factors-and-its-overexpression-impairs-mrna-metabolism
#14
Yen-Ming Lin, Pao-Hsien Chu, Yun-Zhu Li, Pin Ouyang
The nucleolus acts as a key stress sensor and responds to changes in cellular growth rate and metabolic activity. In addition to its major role as the site of ribosome biogenesis, high-throughput proteomic analyses of purified nucleoli have highlighted the multi-functional nature of these organelles, and several SR family splicing factors, including SRSF1 and SRSF2, have been detected in human nucleolar proteome analysis. Here we provide evidence that pNO40, a 60s ribosomal protein associated with nucleoli, acts as a mediator for recruitment of SR family splicing factors into nucleoli...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28065786/cisplatin-induced-necroptosis-in-tnf%C3%AE-dependent-and-independent-pathways
#15
Yanfang Xu, Hua-Bin Ma, Yu-Lu Fang, Zhi-Rong Zhang, Jing Shao, Mao Hong, Chao-Jun Huang, Jing Liu, Rui-Qing Chen
Cisplatin is a chemotherapeutic drug for treatment of many solid tumors. It has been shown to induce apoptosis and/or necrosis in different types of cancer cells. However, the underlying mechanisms remain elusive. In this study, we provide evidences that cisplatin induces necroptosis in receptor-interacting protein 3 (RIP3)-expressing cell lines, but not in cell lines lacking RIP3 protein expression. Deficiency of core components of necroptotic pathway, RIP1, RIP3, or mixed lineage kinase domain-like protein (MLKL) blocked cisplatin-induced cell death in L929 cells...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28065785/a-positive-feedback-loop-between-ros-and-mxi1-0-promotes-hypoxia-induced-vegf-expression-in-human-hepatocellular-carcinoma-cells
#16
Zhenzhen Hu, Na Dong, Dian Lu, Xiuqin Jiang, Jinjin Xu, Zhiwei Wu, Datong Zheng, Daniel S Wechsler
VEGF expression induced by hypoxia plays a critical role in promoting tumor angiogenesis. However, the molecular mechanism that modulates VEGF expression under hypoxia is still poorly understood. In this study, we found that VEGF induction in hypoxic HepG2 cells is ROS-dependent. ROS mediates hypoxia-induced VEGF by upregulation of Mxi1-0. Furthermore, PI3K/AKT/HIF-1α signaling pathway is involved in ROS-mediated Mxi1-0 and VEGF expression in hypoxic HepG2 cells. Finally, Mxi1-0 could in turn regulate ROS generation in hypoxic HepG2 cells, creating a positive feedback loop...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28065784/role-of-phosphatidylserine-in-the-activation-of-rho1-related-pkc1-signaling-in-saccharomyces-cerevisiae
#17
Wataru Nomura, Yusuke Ito, Yoshiharu Inoue
Protein kinase C (PKC) belongs to a family of serine/threonine kinases and is evolutionary conserved among eukaryotes. It contains several functional domains, with the C1 domain being identified as a membrane-targeting module. Diacylglycerol (DAG) and phorbol esters bind to the C1 domain to enhance its kinase activity. The C1 domain is conserved in PKC (Pkc1) in the budding yeast Saccharomyces cerevisiae; however, its kinase activity does not respond to DAG. Although the C1 domain of Pkc1 physically interacts with the small GTPase Rho1, the interaction between C1 domain and lipids has not yet been characterized...
January 5, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28057520/molecular-basis-for-the-regulation-of-the-circadian-clock-kinases-ck1%C3%AE-and-ck1%C3%AE%C2%B5
#18
REVIEW
Yu Yang, Tingting Xu, Yunfei Zhang, Ximing Qin
CK1δ and CK1ε are unique in the casein kinase 1 family and play critical roles in a number of physiological intracellular pathways. In particular, these kinases are involved in composing the mammalian circadian clock by phosphorylating core clock proteins. Considering that CK1δ/ε phosphorylate other key biological molecules, such as β-catenin and p53, understanding how the kinase activity is regulated would be greatly significant, since they are potential targets to develop pharmacological agents against cancer, pain, and circadian disorders...
January 3, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28038963/phosphorylated-cis-suppresses-the-epo-or-jak2-v617f-mutant-triggered-cell-proliferation-through-binding-to-epor
#19
Megumi Funakoshi-Tago, Takuro Moriwaki, Fumihito Ueda, Hiroomi Tamura, Tadashi Kasahara, Kenji Tago
The JAK2 V617F mutant-mediated aberrant signaling pathway is a hallmark of myeloproliferative neoplasms (MPNs). Although cytokine-inducible Src homology 2 protein (CIS) and suppressors of cytokine signaling (SOCS) are negative regulators of the JAK-STAT pathway, the functional role of CIS/SOCS family members in the JAK2 V617F mutant-induced oncogenic signaling pathway has not yet been elucidated. In this study, we found that the expression of CIS and SOCS1 was induced through the activation of signal transducer and activator of transcription 5 (STAT5) in not only the cells stimulated with Epo or IL-3 but also the cells transformed by the JAK2 V617F mutant...
December 28, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/28024901/cyclin-dependent-kinase-5-contributes-to-endoplasmic-reticulum-stress-induced-podocyte-apoptosis-via-promoting-mekk1-phosphorylation-at-ser280-in-diabetic-nephropathy
#20
Yue Zhang, Xiang Gao, Shuanggang Chen, Min Zhao, Jing Chen, Rui Liu, Shengyang Cheng, Mengyuan Qi, Shuo Wang, Wei Liu
Endoplasmic reticulum (ER) stress has been reported to be associated with podocyte apoptosis in diabetic nephropathy, but the mechanism of ER signaling in podocyte apoptosis hasn't been fully understood. Our previous studies have demonstrated that Cyclin-dependent kinase 5 (Cdk5) was associated with podocyte apoptosis in diabetic nephropathy. The present study was designed to examine whether and how Cdk5 activity plays a role in ER stress induced podocyte apoptosis in diabetic nephropathy. The results showed that along with induction of Cdk5 and apoptosis, GRP78 and its two sensors as well as CHOP and cleaved caspase-12 were induced in high glucose treated podocytes...
December 24, 2016: Cellular Signalling
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