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MST1 AND beta cells

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https://www.readbyqxmd.com/read/27883091/mycobacterium-tuberculosis-triggered-hippo-pathway-orchestrates-cxcl1-2-expression-to-modulate-host-immune-responses
#1
Monoranjan Boro, Vikas Singh, Kithiganahalli Narayanaswamy Balaji
Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. Chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. Here, we demonstrate that Hippo (mammalian sterile 20-like 1 and 2 kinases, MST1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27053234/mst1-a-promising-therapeutic-target-to-restore-functional-beta-cell-mass-in-diabetes
#2
REVIEW
Amin Ardestani, Kathrin Maedler
The loss of insulin-producing beta cells by apoptosis is a hallmark of all forms of diabetes mellitus. Strategies to prevent beta cell apoptosis and dysfunction are urgently needed to restore the insulin-producing cells and to prevent severe diabetes progression. We recently identified the serine/threonine kinase known as mammalian sterile 20-like kinase 1 (MST1) as a critical regulator of apoptotic beta cell death and dysfunction. MST1 activates several apoptotic signalling pathways, which further stimulate its own cleavage, leading to a vicious cycle of cell death...
September 2016: Diabetologia
https://www.readbyqxmd.com/read/25600225/mst1-inhibition-rescues-%C3%AE-1-adrenergic-cardiomyopathy-by-reducing-myocyte-necrosis-and-non-myocyte-apoptosis-rather-than-myocyte-apoptosis
#3
Grace J Lee, Lin Yan, Dorothy E Vatner, Stephen F Vatner
It is generally held that inhibition of mammalian sterile 20-like kinase 1 (Mst1) protects the heart through reducing myocyte apoptosis. We determined whether inhibition with a dominant-negative Mst1 (DN-Mst1) would protect against the cardiomyopathy induced by chronic β1-adrenergic receptor (β1-AR) stimulation by preventing myocyte apoptosis. DN-Mst1 mice were mated with β1-AR transgenic (Tg) mice and followed for 20 months. β1-AR Tg mice developed cardiomyopathy as they aged, as reflected by premature mortality and depressed cardiac function, which were rescued in β1-AR × DN-Mst1 bigenic mice...
March 2015: Basic Research in Cardiology
https://www.readbyqxmd.com/read/24841766/mammalian-sterile-like-1-kinase-inhibits-tgf%C3%AE-and-egf%C3%A2-dependent-regulation-of-invasiveness-migration-and-proliferation-of-hec-1-a-endometrial-cancer-cells
#4
Sanaz Attarha, Sonia Andersson, Miriam Mints, Serhiy Souchelnytskyi
Transforming growth factor-β (TGFβ) and epidermal growth factor (EGF) are two potent regulators of tumorigenesis. Signaling cross-talk of TGFβ and EGF employs a number of regulators which define the impact on cell physiology. MST1 has recently been reported as a regulator of tumorigenesis and differentiation. To investigate the role of mammalian sterile-like 1 (MST1) in TGFβ and EGF signaling, we established transiently MST1‑transfected HEC-1-A endometrial cancer cells, and subjected the cells to treatment with TGFβ1, EGF and their combination...
August 2014: International Journal of Oncology
https://www.readbyqxmd.com/read/24633305/mst1-is-a-key-regulator-of-beta-cell-apoptosis-and-dysfunction-in-diabetes
#5
Amin Ardestani, Federico Paroni, Zahra Azizi, Supreet Kaur, Vrushali Khobragade, Ting Yuan, Thomas Frogne, Wufan Tao, Jose Oberholzer, Francois Pattou, Julie Kerr Conte, Kathrin Maedler
Apoptotic cell death is a hallmark of the loss of insulin-producing beta cells in all forms of diabetes mellitus. Current treatments fail to halt the decline in functional beta cell mass, and strategies to prevent beta cell apoptosis and dysfunction are urgently needed. Here, we identified mammalian sterile 20-like kinase-1 (MST1) as a critical regulator of apoptotic beta cell death and function. Under diabetogenic conditions, MST1 was strongly activated in beta cells in human and mouse islets and specifically induced the mitochondrial-dependent pathway of apoptosis through upregulation of the BCL-2 homology-3 (BH3)-only protein BIM...
April 2014: Nature Medicine
https://www.readbyqxmd.com/read/24180524/mammalian-sterile-20-like-kinase-1-2-inhibits-the-wnt-%C3%AE-catenin-signalling-pathway-by-directly-binding-casein-kinase-1%C3%AE%C2%B5
#6
Fei Xu, Yan-Lin Wang, Jiao-Jiao Chang, Si-Chen Du, Lei Diao, Nan Jiang, Hui-Jun Wang, Duan Ma, Jin Zhang
The Hippo signalling pathway can suppress the Wnt/β-catenin signalling pathway through the last downstream effectors YAP (Yes-associated protein)/TAZ (tafazzin). MST (mammalian sterile 20-like kinase) 1 functions as the upstream kinase of the Hippo pathway, and CK1ε (casein kinase 1ε) plays roles in the up-stream signal transduction of the Wnt/β-catenin pathway. In the present study, using tandem affinity purification and MS analysis, CK1ε was identified as a novel partner of MST1. Further analysis showed that the interaction between MST1 and CK1ε was mediated by their kinase domains and enhanced by the activation of MST1...
February 15, 2014: Biochemical Journal
https://www.readbyqxmd.com/read/23661003/foxo3a-is-activated-and-executes-neuron-death-via-bim-in-response-to-%C3%AE-amyloid
#7
P Sanphui, S C Biswas
The molecules that mediate death of selective neurons in Alzheimer's disease (AD) are mostly unknown. The Forkhead transcription factor FoxO3a has emerged as an important mediator of cell fate including apoptosis. When phosphorylated by Akt, it is localized in the cytosol as an inactive complex bound with 14-3-3 protein. For activation and localization of FoxO3a in the nucleus, further modifications are required, such as phosphorylation by mammalian sterile 20-like kinase 1 (MST1) and arginine methylation by protein arginine methyltransferase1...
May 9, 2013: Cell Death & Disease
https://www.readbyqxmd.com/read/23620511/hippo-foxa2-signaling-pathway-plays-a-role-in-peripheral-lung-maturation-and-surfactant-homeostasis
#8
Chaeuk Chung, Tackhoon Kim, Miju Kim, Minchul Kim, Hoogeun Song, Tae-Shin Kim, Eunjeong Seo, Sang-Hee Lee, Hanbyul Kim, Sang Kyum Kim, Geon Yoo, Da-Hye Lee, Deog-Su Hwang, Tatsuo Kinashi, Jin-Man Kim, Dae-Sik Lim
Respiratory distress syndrome (RDS), which is induced by insufficient production of surfactant, is the leading cause of mortality in preterm babies. Although several transcription factors are known to be involved in surfactant protein expression, the molecular mechanisms and signaling pathways upstream of these transcription factors have remained elusive. Here, using mammalian Hippo kinases (Mst1/2, mammalian sterile 20-like kinase 1/2) conditional knockout mice, we demonstrate that Mst1/2 kinases are critical for orchestration of transcription factors involved in surfactant protein homeostasis and prevention of RDS...
May 7, 2013: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/20716165/systematic-assessment-of-protein-phenotypes-characterizing-high-grade-tumour-budding-in-mismatch-repair-proficient-colorectal-cancer
#9
Eva Karamitopoulou, Alessandro Lugli, Ioannis Panayiotides, Petros Karakitsos, George Peros, George Rallis, Efstratios S Patsouris, Luigi Terracciano, Inti Zlobec
AIMS: A tumour bud is defined as a single tumour cell or tumour cell cluster of up to five cells at the invasive tumour front. Significant differences in survival have been detected in colorectal cancer patients with low- compared to high-grade budding. The aim of this study was to identify potential multi-marker phenotypes characterizing low- and high-grade budding in mismatch repair (MMR)-proficient colorectal cancer. METHODS AND RESULTS: Established and promising prognostic proteins such as epidermal growth factor receptor (EGFR), pERK, RHAMM, RKIP, beta-catenin, E-cadherin, pAKT, p16, p21, Ki67, Bcl-2, vascular endothelial growth factor (VEGF), apoptotic protease activating factor-1 (APAF-1), MUC1, EphB2, matrix metalloproteinase 7, pSMAD2, CDX2, laminin5gamma2 and MST1 were analysed on 208 MMR-proficient colorectal cancers with complete clinicopathological data...
August 2010: Histopathology
https://www.readbyqxmd.com/read/19729020/selective-activation-of-the-b-splice-variant-of-phospholipase-cbeta1-in-chronically-dilated-human-and-mouse-atria
#10
Elizabeth A Woodcock, David R Grubb, Theresa M Filtz, Silvana Marasco, Jieting Luo, Tiffany J McLeod-Dryden, David M Kaye, Junichi Sadoshima, Xiao-Jun Du, Chiew Wong, Julie R McMullen, Anthony M Dart
Atrial fibrillation (AF) is commonly associated with chronic dilatation of the left atrium, both in human disease and animal models. The immediate signaling enzyme phospholipase C (PLC) is activated by mechanical stretch to generate the Ca2+-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and sn-1,2-diacylglycerol (DAG), an activator of protein kinase C subtypes. There is also evidence that heightened activity of PLC, caused by the receptor coupling protein Gq, can contribute to atrial remodelling...
November 2009: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/19060893/apoptotic-histone-modification-inhibits-nuclear-transport-by-regulating-rcc1
#11
Chi-Hang Wong, Hei Chan, Chin-Yee Ho, Soak-Kuan Lai, Kheng-Sze Chan, Cheng-Gee Koh, Hoi-Yeung Li
A number of signalling pathways have been identified that regulate apoptosis, but the mechanism that initiates apoptosis remains incompletely understood. We have found that the nuclear RanGTP level is diminished during the early stages of apoptosis, which correlates with immobilization of RCC1 on the chromosomes. Furthermore, the expression of phosphomimetic histone H2B or caspase-activated Mst1 immobilizes RCC1 and causes reduction of nuclear RanGTP levels, which leads to inactivation of the nuclear transport machinery...
January 2009: Nature Cell Biology
https://www.readbyqxmd.com/read/18670060/gene-expression-profiling-in-skeletal-muscle-of-holstein-friesian-bulls-with-single-nucleotide-polymorphism-in-the-myostatin-gene-5-flanking-region
#12
Tomasz Sadkowski, Michał Jank, Lech Zwierzchowski, Eulalia Siadkowska, Jolanta Oprzadek, Tomasz Motyl
Myostatin (GDF-8) is a key protein responsible for skeletal muscle growth and development, thus mutations in the mstn gene can have major economic and breeding consequences. The aim of the present study was to investigate myostatin gene expression and transcriptional profile in skeletal muscle of Holstein-Friesian (Black-and-White) bulls carrying a polymorphism in the 5'-flanking region of the mstn gene (G/C transversion at position -7828). Real-time qRT-PCR and cDNA microarray revealed significantly lower mstn expression in muscle of bulls with the CC genotype, as compared to GG and GC genotypes...
2008: Journal of Applied Genetics
https://www.readbyqxmd.com/read/17680267/effects-of-season-long-high-temperature-growth-conditions-on-sugar-to-starch-metabolism-in-developing-microspores-of-grain-sorghum-sorghum-bicolor-l-moench
#13
Mukesh Jain, P V Vara Prasad, Kenneth J Boote, Allen L Hartwell, Prem S Chourey
High temperature stress-induced male sterility is a critical problem in grain sorghum (Sorghum bicolor L. Moench) that significantly compromises crop yields. Grain sorghum plants were grown season-long under ambient (30/20 degrees C, day-time maximum/night-time minimum) and high temperature (36/26 degrees C) conditions in sunlit Soil-Plant-Atmospheric-Research (SPAR) growth chambers. We report data on the effects of high temperature on sugar levels and expression profiles of genes related to sugar-to-starch metabolism in microspore populations represented by pre- and post-meiotic "early" stages through post-mitotic "late" stages that show detectable levels of starch deposition...
December 2007: Planta
https://www.readbyqxmd.com/read/17372272/mst1-ranbp2-and-eif4g-are-new-markers-for-in-vivo-pi3k-activation-in-murine-and-human-prostate
#14
Oliver Renner, Jesus Fominaya, Soledad Alonso, Carmen Blanco-Aparicio, Juan F M Leal, Amancio Carnero
Phosphatidylinositol 3-kinases (PI3Ks) constitute important regulators of signaling pathways. The PIK3CA gene encoding the p110-alpha catalytic subunit represents one of the highly mutated oncogenes identified in human cancer. Here, we report new markers for in vivo PI3K activation in prostate. To that end, we used a transgenic mouse line, which expresses a constitutively active p110-alpha subunit in the epithelial cells of the prostate. The activity of the PI3K pathway in the prostate was proven by assessing the phosphorylation of the PI3K direct target AKT1 and of the mTOR target eukaryotic translation initiation factor 4G (eIF4G)...
July 2007: Carcinogenesis
https://www.readbyqxmd.com/read/11278283/mst-a-physiological-caspase-substrate-highly-sensitizes-apoptosis-both-upstream-and-downstream-of-caspase-activation
#15
K K Lee, T Ohyama, N Yajima, S Tsubuki, S Yonehara
The human serine/threonine kinase, mammalian STE20-like kinase (MST), is considerably homologous to the budding yeast kinases, SPS1 and STE20, throughout their kinase domains. The cellular function and physiological activation mechanism of MST is unknown except for the proteolytic cleavage-induced activation in apoptosis. In this study, we show that MST1 and MST2 are direct substrates of caspase-3 both in vivo and in vitro. cDNA cloning of MST homologues in mouse and nematode shows that caspase-cleaved sequences are evolutionarily conserved...
June 1, 2001: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/10980603/spak-a-ste20-sps1-related-kinase-that-activates-the-p38-pathway
#16
COMPARATIVE STUDY
A M Johnston, G Naselli, L J Gonez, R M Martin, L C Harrison, H J DeAizpurua
We have cloned a member of the STE20/SPS1 protein kinase family from a transformed rat pancreatic beta cell line. SPAK (STE20/SPS1-related, proline alanine-rich kinase) belongs to the SPS1 subfamily of STE20 kinases and is highly conserved between species. SPAK is expressed ubiquitously, although preferentially in brain and pancreas. Biochemical characterization of SPAK catalytic activity demonstrates that is a serine/threonine kinase that can phosphorylate itself and an exogenous substrate in vitro. SPAK is immunoprecipitated from transfected mammalian cells as a complex with another, as yet uncharacterized, serine/threonine kinase which is capable of phosphorylating catalytically-inactive SPAK and myelin basic protein in an in vitro kinase assay...
August 31, 2000: Oncogene
https://www.readbyqxmd.com/read/9101469/p16-overexpression-a-potential-early-indicator-of-transformation-in-ovarian-carcinoma
#17
COMPARATIVE STUDY
K Shigemasa, C Hu, C M West, J Clarke, G P Parham, T H Parmley, S Korourian, V V Baker, T J O'Brien
OBJECTIVE: The recently cloned gene p16 (MST1) has been identified as a putative tumor suppressor gene that binds to CDK4 and CDK6 (cyclin-dependent kinases), preventing their interaction with cyclin D1 and thereby preventing cell cycle progression at the G1 stage. In addition, the p16 gene has been shown to have a high frequency of mutation in some tumor cell lines; however, it has also been shown that a much lower frequency of mutation occurs in primary tumors. This study investigated the mRNA expression level and mutation status of the p16 gene in ovarian tumors...
March 1997: Journal of the Society for Gynecologic Investigation
https://www.readbyqxmd.com/read/8252064/a-sink-specific-h-monosaccharide-co-transporter-from-nicotiana-tabacum-cloning-and-heterologous-expression-in-baker-s-yeast
#18
N Sauer, R Stadler
A cDNA clone for a monosaccharide transporter (MST1) was isolated from tobacco, which is most strongly expressed in the various sink tissues of mature tobacco plants: roots, flowers, and young leaves. An open reading frame of 1569 bp codes for a protein with 523 amino acids and a calculated molecular weight of 57,717 Da. The protein is homologous to a group of other plant monosaccharide transport proteins from Arabidopsis thaliana and Chlorella kessleri, to human glucose transporters and to Saccharomyces cerevisiae and several bacterial sugar transport proteins...
October 1993: Plant Journal: for Cell and Molecular Biology
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