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rho kinase and endoplasmic reticulum

Jacey H Ma, Joshua J Wang, Junhua Li, Bruce A Pfeffer, Yiming Zhong, Sarah X Zhang
Purpose: The retinal pigment epithelium (RPE) tight junctions play a pivotal role in maintaining the homeostatic environment of the neural retina. Herein, we investigated the role of X-box binding protein 1 (XBP1), an endoplasmic reticulum (ER) stress-responsive transcription factor, in regulation of RPE tight junctions. Methods: Human RPE cell line (ARPE-19) and primary primate RPE cells were used for in vitro experiments and RPE-specific XBP1 knockout (KO) mice were used for in vivo study...
October 1, 2016: Investigative Ophthalmology & Visual Science
Chao Li, Fang-Ling Yeh, Alice Y Cheung, Qiaohong Duan, Daniel Kita, Ming-Che Liu, Jacob Maman, Emily J Luu, Brendan W Wu, Laura Gates, Methun Jalal, Amy Kwong, Hunter Carpenter, Hen-Ming Wu
The Arabidopsis receptor kinase FERONIA (FER) is a multifunctional regulator for plant growth and reproduction. Here we report that the female gametophyte-expressed glycosylphosphatidylinositol-anchored protein (GPI-AP) LORELEI and the seedling-expressed LRE-like GPI-AP1 (LLG1) bind to the extracellular juxtamembrane region of FER and show that this interaction is pivotal for FER function. LLG1 interacts with FER in the endoplasmic reticulum and on the cell surface, and loss of LLG1 function induces cytoplasmic retention of FER, consistent with transport of FER from the endoplasmic reticulum to the plasma membrane in a complex with LLG1...
2015: ELife
Ga Bin Park, Dae Young Hur, Daejin Kim
BACKGROUND: Phosphoinositide-3 kinase (PI3K) inhibition attenuates proliferation and survival in B-cell malignancies. Celecoxib induces endoplasmic reticulum (ER) stress-induced apoptosis via a cyclo-oxgenase-2 (COX2)-independent manner in certain types of cancer cells. In the present study, we assessed the effects of combinations of drugs with a p110δ-specific inhibitor, CAL-101, and celecoxib to induce apoptosis in Epstein-Barr virus (EBV)-transformed B-cells and non-Hodgkin's lymphoma (NHL) cells...
May 2015: Anticancer Research
Qiang Li, Bo Chen, Chong Zeng, Aihui Fan, Yongjun Yuan, Xiaohua Guo, Xuliang Huang, Qiaobing Huang
What is the central question of this study? Why do different doses of sphingosine-1-phosphate (S1P) induce distinct biological effects in endothelial cells? What is the main finding and its importance? S1P at physiological concentrations preserved endothelial barrier function by binding to S1P receptor 1, then triggering Ca(2+) release from endoplasmic reticulum through phosphoinositide phospholipase C and inositol triphosphate, and consequently strengthening tight junction and F-actin assembly through Rac1 activation...
January 2015: Experimental Physiology
Jisheng Chen, Zhenbiao Yang
ROP GTPases (Rho-like GTPase from plants), plant counterparts of animal and fungal Rho-family GTPases, have recently been shown to be key components of a novel signaling pathway activated by the plant hormone auxin. Auxin (indole acetic acid) is a key regulator of virtually every aspect of plant growth and development, yet the molecular mechanisms of auxin responses remain largely unknown. AUXIN BINDING PROTEIN1 (ABP1) is an ancient protein that binds auxin and has been implied as a receptor for a number of auxin responses, but its precise mechanism remains unresolved...
June 30, 2014: Small GTPases
Natalia V Oleinik, Kristi L Helke, Emily Kistner-Griffin, Natalia I Krupenko, Sergey A Krupenko
Folate, an important nutrient in the human diet, has been implicated in cancer, but its role in metastasis is not established. We have shown previously that the withdrawal of medium folate leads to the inhibition of migration and invasion of A549 lung carcinoma cells. Here we have demonstrated that medium folate regulates the function of Rho GTPases by enabling their carboxyl methylation and translocation to plasma membrane. Conversely, the lack of folate leads to the retention of these proteins in endoplasmic reticulum...
September 19, 2014: Journal of Biological Chemistry
Jisheng Chen, Zhenbiao Yang
ROP GTPases (Rho-like GTPase from plants), plant counterparts of animal and fungal Rho-family GTPases, have recently been shown to be key components of a novel signaling pathway activated by the plant hormone auxin. Auxin (indole acetic acid) is a key regulator of virtually every aspect of plant growth and development, yet the molecular mechanisms of auxin responses remain largely unknown. AUXIN BINDING PROTEIN1 (ABP1) is an ancient protein that binds auxin and has been implied as a receptor for a number of auxin responses, but its precise mechanism remains unresolved...
June 30, 2014: Small GTPases
Ronit Sharon-Friling, Thomas Shenk
The human cytomegalovirus immediate-early protein pUL37x1 induces the release of Ca(2+) stores from the endoplasmic reticulum into the cytosol. This release causes reorganization of the cellular actin cytoskeleton with concomitant cell rounding. Here we demonstrate that pUL37x1 activates Ca(2+)-dependent protein kinase Cα (PKCα). Both PKCα and Rho-associated protein kinases are required for actin reorganization and cell rounding; however, only PKCα is required for the efficient production of virus progeny, arguing that HCMV depends on the kinase for a second function...
March 25, 2014: Proceedings of the National Academy of Sciences of the United States of America
Ana Griciuc, Michel J Roux, Juliane Merl, Angela Giangrande, Stefanie M Hauck, Liviu Aron, Marius Ueffing
Inherited mutations that lead to misfolding of the visual pigment rhodopsin (Rho) are a prominent cause of photoreceptor neuron (PN) degeneration and blindness. How Rho proteotoxic stress progressively impairs PN viability remains unknown. To identify the pathways that mediate Rho toxicity in PNs, we performed a comprehensive proteomic profiling of retinas from Drosophila transgenics expressing Rh1(P37H), the equivalent of mammalian Rho(P23H), the most common Rho mutation linked to blindness in humans. Profiling of young Rh1(P37H) retinas revealed a coordinated upregulation of energy-producing pathways and attenuation of energy-consuming pathways involving target of rapamycin (TOR) signaling, which was reversed in older retinas at the onset of PN degeneration...
February 19, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Olga S Sizova, Vishal M Shinde, Austin R Lenox, Marina S Gorbatyuk
We previously reported activation of the unfolded protein response (UPR) in P23H rhodopsin (RHO) retinas with autosomal dominant retinitis pigmentosa (ADRP). Knowing that the UPR can trigger Ca(2+) release from the endoplasmic reticulum and regulate cellular signaling we examined the level of Ca(2+)-regulated proteins. We also looked for changes in the expression of Bcl2 family proteins, autophagy proteins and the mTOR/AKT pathways, as well as for the induction of mitochondria-associated apoptosis in the P23H RHO retina...
April 2014: Cellular Signalling
Carlos O Arregui, Ángela González, Juan E Burdisso, Ana E González Wusener
Cell migration requires a highly coordinated interplay between specialized plasma membrane adhesion complexes and the cytoskeleton. Protein phosphorylation/dephosphorylation modifications regulate many aspects of the integrin-cytoskeleton interdependence, including their coupling, dynamics, and organization to support cell movement. The endoplasmic reticulum-bound protein tyrosine phosphatase PTP1B has been implicated as a regulator of cell adhesion and migration. Recent results from our laboratory shed light on potential mechanisms, such as Src/FAK signaling through Rho GTPases and integrin-cytoskeletal coupling...
September 2013: Cell Adhesion & Migration
Eui-Soon Park, Juhyeok Kim, Tae-uk Ha, Jong-Soon Choi, Kwan Soo Hong, Jaerang Rho
Apoptosis has an important role in maintaining tissue homeostasis in cellular stress responses such as inflammation, endoplasmic reticulum stress, and oxidative stress. T-cell death-associated gene 51 (TDAG51) is a member of the pleckstrin homology-like domain family and was first identified as a pro-apoptotic gene in T-cell receptor-mediated cell death. However, its pro-apoptotic function remains controversial. In this study, we investigated the role of TDAG51 in oxidative stress-induced apoptotic cell death in mouse embryonic fibroblasts (MEFs)...
2013: Experimental & Molecular Medicine
Michelle J Connolly, Jesus Prieto-Lloret, Silke Becker, Jeremy P T Ward, Philip I Aaronson
  Hypoxic pulmonary vasoconstriction (HPV) maintains blood oxygenation during acute hypoxia but contributes to pulmonary hypertension during chronic hypoxia. The mechanisms of HPV remain controversial, in part because HPV is usually studied in the presence of agonist-induced preconstriction ('pretone'). This potentiates HPV but may obscure and distort its underlying mechanisms. We therefore carried out an extensive assessment of proposed mechanisms contributing to HPV in isolated intrapulmonary arteries (IPAs) in the absence of pretone by using a conventional small vessel myograph...
September 15, 2013: Journal of Physiology
Shun Lei, Yan-Ping Tian, Wei-Dong Xiao, Shu Li, Xian-Cai Rao, Jun-Lei Zhang, Jie Yang, Xiao-Mei Hu, Wei Chen
Our previous study showed that dengue virus 2 (DENV2) infection induces rearrangement of vimentin into dense structures at the perinuclear area. However, the underlying mechanism of this phenomenon is poorly characterized. In the present work, we found that vimentin and Ser71 phosphorylated vimentin display similar distributions in DENV2-infected cells. DENV2 infection also induced ROCK activation and phosphorylation of vimentin at Ser71 as the DENV2 infection progressed. Furthermore, Ser71 phosphorylation and vimentin rearrangement induced by DENV2 infection were blocked by the ROCK inhibitor Y-27632...
2013: Cell Biochemistry and Biophysics
Daiji Kawanami, Keiichiro Matoba, Rina Okada, Masami Tsukamoto, Jun Kinoshita, Sho Ishizawa, Yasushi Kanazawa, Tamotsu Yokota, Kazunori Utsunomiya
The process of atherosclerosis is affected by interactions among numerous biological pathways. Accumulating evidence shows that endoplasmic reticulum (ER) stress plays a crucial role in the development of atherosclerosis. Rho-kinase is an effector of small GTP-binding protein Rho, and has been implicated as an atherogenic factor. Previous studies demonstrated that fasudil, a specific Rho-kinase inhibitor, exerts a cardioprotective effect by downregulating ER stress signaling. However, the molecular link between ER stress and Rho-kinase in endothelial cells has not been elucidated...
May 31, 2013: Biochemical and Biophysical Research Communications
Xiaojuan Chi, Song Wang, Yifan Huang, Mark Stamnes, Ji-Long Chen
Rho family GTPases belong to the Ras GTPase superfamily and transduce intracellular signals known to regulate a variety of cellular processes, including cell polarity, morphogenesis, migration, apoptosis, vesicle trafficking, viral transport and cellular transformation. The three best-characterized Rho family members are Cdc42, RhoA and Rac1. Cdc42 regulates endocytosis, the transport between the endoplasmic reticulum and Golgi apparatus, post-Golgi transport and exocytosis. Cdc42 influences trafficking through interaction with Wiskott-Aldrich syndrome protein (N-WASP) and the Arp2/3 complex, leading to changes in actin dynamics...
2013: International Journal of Molecular Sciences
Yapeng Li, Wei Zhu, Jianping Tao, Ping Xin, Mingya Liu, Jingbo Li, Meng Wei
Disordered calcium homeostasis can lead to endoplasmic reticulum (ER) stress. Our previous data showed that time course activation of ER stress contributes to time-related increase in ischemia-reperfusion (I/R) injury. However, it has not been tested whether PI3K/Akt and JAK2/STAT3 pathways play differential roles in reducing ER stress to protect the heart. In the present study, using fasudil which is a specific inhibitor of ROCK, we aimed to investigate whether improved SERCA expression and activity accounts for reduced ER stress by ROCK inhibition, specifically whether PI3K/Akt and JAK2/STAT3 pathways are differentially involved in modulating SERCA activity to reduce ER stress and hence I/R injury...
2012: PloS One
Panpan Chen, Steven D Douglas, John Meshki, Florin Tuluc
Cell-derived microparticles participate in intercellular communication similar to the classical messenger systems of small and macro-molecules that bind to specialized membrane receptors. Microparticles have been implicated in the regulation of a variety of complex physiopathologic processes, such as thrombosis, the control of innate and adaptive immunity, and cancer. The neurokinin 1 receptor (NK1R) is a Gq-coupled receptor present on the membrane of a variety of tissues, including neurons in the central and peripheral nervous system, immune cells, endocrine and exocrine glands, and smooth muscle...
2012: PloS One
Nichola Cruickshanks, Yong Tang, Laurence Booth, Hossein Hamed, Steven Grant, Paul Dent
Previous studies showed that lapatinib and obatoclax interact in a greater-than-additive fashion to cause cell death and do so through a toxic form of autophagy. The present studies sought to extend our analyses. Lapatinib and obatoclax killed multiple tumor cell types, and cells lacking phosphatase and tensin homolog (PTEN) function were relatively resistant to drug combination lethality; expression of PTEN in PTEN-null breast cancer cells restored drug sensitivity. Coadministration of lapatinib with obatoclax elicited autophagic cell death that was attributable to the actions of mitochondrial reactive oxygen species...
December 2012: Molecular Pharmacology
Vishal M Shinde, Olga S Sizova, Jonathan H Lin, Matthew M LaVail, Marina S Gorbatyuk
The S334ter rhodopsin (Rho) rat (line 4) bears the rhodopsin gene with an early termination codon at residue 334 that is a model for several such mutations found in human patients with autosomal dominant retinitis pigmentosa (ADRP). The Unfolded Protein Response (UPR) is implicated in the pathophysiology of several retinal disorders including ADRP in P23H Rho rats. The aim of this study was to examine the onset of UPR gene expression in S334ter Rho retinas to determine if UPR is activated in ADRP animal models and to investigate how the activation of UPR molecules leads to the final demise of S334ter Rho photoreceptors...
2012: PloS One
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