PX-RICS Mediates ER-To-Golgi Transport of the N-Cadherin/-Catenin Complex
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The Proximal Signaling Network of the BCR-ABL1 Oncogene Shows a Modular Organization
Oncogene (2010) 29, 5895–5910 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc ORIGINAL ARTICLE The proximal signaling network of the BCR-ABL1 oncogene shows a modular organization B Titz, T Low, E Komisopoulou, SS Chen, L Rubbi and TG Graeber Crump Institute for Molecular Imaging, Institute for Molecular Medicine, Jonsson Comprehensive Cancer Center, California NanoSystems Institute, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA BCR-ABL1 is a fusion tyrosine kinase, which causes signaling effects of BCR-ABL1 toward leukemic multiple types of leukemia. We used an integrated transformation. proteomic approach that includes label-free quantitative Oncogene (2010) 29, 5895–5910; doi:10.1038/onc.2010.331; protein complex and phosphorylation profiling by mass published online 9 August 2010 spectrometry to systematically characterize the proximal signaling network of this oncogenic kinase. The proximal Keywords: adaptor protein; BCR-ABL1; phospho- BCR-ABL1 signaling network shows a modular and complex; quantitative mass spectrometry; signaling layered organization with an inner core of three leukemia network; systems biology transformation-relevant adaptor protein complexes (Grb2/Gab2/Shc1 complex, CrkI complex and Dok1/ Dok2 complex). We introduced an ‘interaction direction- ality’ analysis, which annotates static protein networks Introduction with information on the directionality of phosphorylation- dependent interactions. In this analysis, the observed BCR-ABL1 is a constitutively active oncogenic fusion network structure was consistent with a step-wise kinase that arises through a chromosomal translocation phosphorylation-dependent assembly of the Grb2/Gab2/ and causes multiple types of leukemia. It is found in Shc1 and the Dok1/Dok2 complexes on the BCR-ABL1 many cases (B25%) of adult acute lymphoblastic core. -
1 Validating Predicted Biological Effects of Alzheimer's Disease
Journal of Alzheimer’s Disease ISSN: 1387-2877 IOS Press DOI: 10.3233/JAD-2010-091711 Validating Predicted Biological Effects of Alzheimer’s Disease Associated SNPs Using CSF Biomarker Levels John S.K. Kauwea,*, Carlos Cruchagab,*, Sarah Bertelsenb, Kevin Mayob, Wayne Latua, Petra Nowotnyb, Anthony L. Hinrichsb, Anne M. Faganc, David M. Holtzmanc, Alzheimer’s Disease Neuroimaging Initiative** and Alison M. Goateb aDepartment of Biology, Brigham Young University, Provo, UT, USA bDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA cDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA *Co-first authors with equal contributions. Running Title: Validating effects of AD risk variants Handling Associate Editor: Daniela Galimberti Accepted 16 April 2010 Correspondence to: Alison M. Goate, PhD, Samuel & Mae S. Ludwig Professor, Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA; Tel: +1 314-362-8691, Fax: +1 314-747-2983, Email: [email protected]. 1 **Some of the data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://www.loni.ucla.edu\ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. ADNI investigators include (complete listing available at http://www.loni.ucla.edu/ADNI/About/About_Investigators.shtml). 2 ABSTRACT Recent large-scale genetic studies of late-onset Alzheimer’s disease have identified risk variants in CALHM1, GAB2, and SORL1. The mechanisms by which these genes might modulate risk are not definitively known. -
Domain Requires the Gab2 Pleckstrin Homology Negative Regulation Of
Ligation of CD28 Stimulates the Formation of a Multimeric Signaling Complex Involving Grb-2-Associated Binder 2 (Gab2), Src Homology Phosphatase-2, and This information is current as Phosphatidylinositol 3-Kinase: Evidence That of October 1, 2021. Negative Regulation of CD28 Signaling Requires the Gab2 Pleckstrin Homology Domain Richard V. Parry, Gillian C. Whittaker, Martin Sims, Downloaded from Christine E. Edmead, Melanie J. Welham and Stephen G. Ward J Immunol 2006; 176:594-602; ; doi: 10.4049/jimmunol.176.1.594 http://www.jimmunol.org/content/176/1/594 http://www.jimmunol.org/ References This article cites 59 articles, 38 of which you can access for free at: http://www.jimmunol.org/content/176/1/594.full#ref-list-1 Why The JI? Submit online. by guest on October 1, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Ligation of CD28 Stimulates the Formation of a Multimeric Signaling Complex Involving Grb-2-Associated Binder 2 (Gab2), Src Homology Phosphatase-2, and Phosphatidylinositol 3-Kinase: Evidence That Negative Regulation of CD28 Signaling Requires the Gab2 Pleckstrin Homology Domain1 Richard V. -
Structure and Function of Gab2 and Its Role in Cancer (Review)
MOLECULAR MEDICINE REPORTS 12: 4007-4014, 2015 Structure and function of Gab2 and its role in cancer (Review) CHEN-BO DING1, WEI-NA YU1, JI-HONG FENG2 and JUN-MIN LUO1 1Department of Immunology and Immunology Innovation Base for Postgraduate Education in Guizhou Province, Zunyi Medical University; 2Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China Received September 11, 2014; Accepted May 19, 2015 DOI: 10.3892/mmr.2015.3951 Abstract. The docking proteins of the Grb-associated binder 1. Introduction (Gab) family transduce cellular signals between receptors and intracellular downstream effectors, and provide a platform Gab2 belongs to the Grb-associated binder (Gab) family of for protein-protein interactions. Gab2, a key member of the docking proteins, which also includes mammalian Gab1, Gab family of proteins, is involved in the amplification and Gab3 and Gab4, Drosophila daughter of sevenless, and integration of signal transduction, evoked by a variety of Caenorhabditis elegans suppressor of Clr-1 (1). Gab2 is extracellular stimuli, including growth factors, cytokines reported to contain a pleckstrin homology (PH) domain at and antigen receptors. Gab2 protein lacks intrinsic catalytic the N-terminus, several proline-rich motifs (PXXP) and activity; however, when phosphorylated by protein-tyrosine multiple tyrosine residues, which couple with SH2-containing kinases (PTKs), Gab2 recruits several Src homology-2 (SH2) molecules in a phosphorylation-dependent manner (1,2). The domain-containing proteins, including the SH2-containing Gab2 PH domain preferentially combines phosphatidylino- protein tyrosine phosphatase 2 (SHP2), the p85 subunit of sitol 3,4,5-P3 (PIP3) (3). In Gab2, two of the proline-rich motifs phosphoinositide-3 kinase (PI3K), phospholipase C-γ (PLCγ)1, are Grb2-Src homology (SH3) domain binding sites (4), which Crk, and GC-GAP. -
Functional Characterization of Epilepsy Associated GABRG2 Mutations
Functional Characterization of Epilepsy Associated GABRG2 Mutations By Mengnan Tian Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in Partial Fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Pharmacology August, 2012 Nashville, Tennessee Approved: Robert L. Macdonald, M.D., Ph.D. Ronald Emeson, Ph.D. Kevin Ess, M.D., Ph.D. Katherine T. Murray, M.D. Douglas P. Mortlock, Ph.D. To my grandparents, Yunbo Tian and Zhenhua Cao. ii Acknowledgements Throughout my years pursuing Ph.D. degree, I have always been grateful for the opportunity working with an amazing complement of scientists. I would like to express my sincerest gratitude to my thesis advisor Dr. Robert Macdonald. He is by far the best mentor that I could have ever wished. He has provided me with excellent guidance and support, and given me the confidence to develop into an independent scientist. He granted me unprecedented freedom to explore new scientific fields and implement novel research strategies and techniques. I greatly appreciate all his trust in me, and it has fostered my confidence in performing researches. He has shown me, by his example, what a good scientist and mentor should be. I would like to thank my colleagues and collaborators in Macdonald lab. I have been collaborating with Xuan Huang since her rotation and after she joined our lab in 2009. We have also become good friends. She has made important contributions to many parts of my thesis studies, and provided brilliant critiques to help me improve the research plan. I am also deeply indebted to Dr. -
Epithelial-To-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems
cancers Article Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems Peiyu Wang 2,3 , Renwu Zhou 4 , Patrick Thomas 2,3,5 , Liqian Zhao 6, Rusen Zhou 4, Susmita Mandal 7, Mohit Kumar Jolly 7, Derek J. Richard 2,3, Bernd H. A. Rehm 8, Kostya (Ken) Ostrikov 9, Xiaofeng Dai 1,*, Elizabeth D. Williams 2,3,4 and Erik W. Thompson 2,3 1 Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China 2 Queensland University of Technology (QUT), School of Biomedical Sciences, Brisbane 4059, Australia 3 Translational Research Institute, Woolloongabba 4102, Australia 4 School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney 2006, Australia 5 Queensland Bladder Cancer Initiative (QBCI), Woolloongabba 4102, Australia 6 The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China 7 Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India 8 Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan 4111, Australia 9 School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia; Citation: Wang, P.; Zhou, R.; * Correspondence: [email protected] Thomas, P.; Zhao, L.; Zhou, R.; Mandal, S.; Jolly, M.K.; Richard, D.J.; Simple Summary: Cold atmospheric plasma (CAP) and plasma-activated medium (PAM) are known Rehm, B.H.A.; Ostrikov, K.; et al. to selectively kill cancer cells, however the efficacy of CAP in cancer cells following epithelial- Epithelial-to-Mesenchymal Transition mesenchymal transition (EMT), a process which endows cancer cells with increased stemness, Enhances Cancer Cell Sensitivity to metastatic potential, and resistance to conventional therapies, has not been previously examined. -
Invasive Bladder Cancer: Genomic Insights and Therapeutic Promise Jaegil Kim1, Rehan Akbani2, Chad J
Review Clinical Cancer Research Invasive Bladder Cancer: Genomic Insights and Therapeutic Promise Jaegil Kim1, Rehan Akbani2, Chad J. Creighton3, Seth P. Lerner3, John N. Weinstein2, Gad Getz1,4, and David J. Kwiatkowski1,5 Abstract Invasive bladder cancer, for which there have been few thera- unusually frequent in comparison with other cancers, and muta- peutic advances in the past 20 years, is a significant medical tion or amplification of transcription factors is also common. problem associated with metastatic disease and frequent mortal- Expression clustering analyses organize bladder cancers into four ity. Although previous studies had identified many genetic altera- principal groups, which can be characterized as luminal, immune tions in invasive bladder cancer, recent genome-wide studies have undifferentiated, luminal immune, and basal. The four groups provided a more comprehensive view. Here, we review those show markedly different expression patterns for urothelial differ- recent findings and suggest therapeutic strategies. Bladder cancer entiation (keratins and uroplakins) and immunity genes (CD274 has a high mutation rate, exceeded only by lung cancer and and CTLA4), among others. These observations suggest numerous melanoma. About 65% of all mutations are due to APOBEC- therapeutic opportunities, including kinase inhibitors and anti- mediated mutagenesis. There is a high frequency of mutations body therapies for genes in the canonical signaling pathways, and/or genomic amplification or deletion events that affect many histone deacetylase inhibitors and novel molecules for chromatin of the canonical signaling pathways involved in cancer develop- gene mutations, and immune therapies, which should be targeted ment: cell cycle, receptor tyrosine kinase, RAS, and PI-3-kinase/ to specific patients based on genomic profiling of their cancers. -
Review Article Potential Peripheral Biomarkers for the Diagnosis of Alzheimer’S Disease
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Crossref SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 572495, 9 pages doi:10.4061/2011/572495 Review Article Potential Peripheral Biomarkers for the Diagnosis of Alzheimer’s Disease Seema Patel, Raj J. Shah, Paul Coleman, and Marwan Sabbagh Banner Sun Health Research Institute, Sun City, AZ 85351, USA Correspondence should be addressed to Marwan Sabbagh, [email protected] Received 10 January 2011; Revised 17 August 2011; Accepted 25 August 2011 Academic Editor: Holly Soares Copyright © 2011 Seema Patel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer’s would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker. -
State-Dependent Calcium Signaling in Dendritic Spines of Striatal Medium Spiny Neurons
Neuron, Vol. 44, 483–493, October 28, 2004, Copyright 2004 by Cell Press State-Dependent Calcium Signaling in Dendritic Spines of Striatal Medium Spiny Neurons Adam G. Carter and Bernardo L. Sabatini* low- and high-threshold voltage-sensitive calcium (Ca) Department of Neurobiology channels (VSCCs), and ionotropic glutamate receptors. Harvard Medical School Multiple neuronal processes in MSNs are regulated by 220 Longwood Avenue Ca influx, including synaptic strength (Calabresi et al., Boston, Massachusetts 02115 1992; Partridge et al., 2000) and gene expression (Kon- radi et al., 1996; Liu and Graybiel, 1996; Rajadhyaksha et al., 1999). MSNs may possess routes for Ca entry not Summary found in other principal neurons, including Ca-perme- able AMPA receptors (AMPARs) (Bernard et al., 1997; Striatal medium spiny neurons (MSNs) in vivo undergo Chen et al., 1998; Stefani et al., 1998). Moreover, Ca large membrane depolarizations known as state tran- sources may be preferentially activated in the two states, sitions. Calcium (Ca) entry into MSNs triggers diverse such as T-type VSCCs capable of activating at relatively downstream cellular processes. However, little is hyperpolarized potentials (McRory et al., 2001). How- known about Ca signals in MSN dendrites and spines ever, little is known about subcellular Ca signals in MSNs and how state transitions influence these signals. and how they are influenced by state transitions. Here, we develop a novel approach, combining 2-pho- In cultured MSNs, upstate transitions are triggered by ton Ca imaging and 2-photon glutamate uncaging, to spontaneous synaptic inputs and can generate dendritic examine how voltage-sensitive Ca channels (VSCCs) Ca signals (Kerr and Plenz, 2002) that are enhanced by and ionotropic glutamate receptors contribute to Ca back-propagating APs (bAPs) (Kerr and Plenz, 2004). -
Network Organization of the Human Autophagy System
Vol 466 | 1 July 2010 | doi:10.1038/nature09204 ARTICLES Network organization of the human autophagy system Christian Behrends1, Mathew E. Sowa1, Steven P. Gygi2 & J. Wade Harper1 Autophagy, the process by which proteins and organelles are sequestered in autophagosomal vesicles and delivered to the lysosome/vacuole for degradation, provides a primary route for turnover of stable and defective cellular proteins. Defects in this system are linked with numerous human diseases. Although conserved protein kinase, lipid kinase and ubiquitin-like protein conjugation subnetworks controlling autophagosome formation and cargo recruitment have been defined, our understanding of the global organization of this system is limited. Here we report a proteomic analysis of the autophagy interaction network in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new autophagy interaction network components have roles in vesicle trafficking, protein or lipid phosphorylation and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. These studies provide a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway. Protein homeostasis in eukaryotes is controlled by proteasomal turn- promote incorporation of Atg8p--PE into autophagosomes, allowing over of unstable proteins via the ubiquitin system and lysosomal turn- Atg8p to promote autophagosome closure and cargo recruitment. -
Drosophila and Human Transcriptomic Data Mining Provides Evidence for Therapeutic
Drosophila and human transcriptomic data mining provides evidence for therapeutic mechanism of pentylenetetrazole in Down syndrome Author Abhay Sharma Institute of Genomics and Integrative Biology Council of Scientific and Industrial Research Delhi University Campus, Mall Road Delhi 110007, India Tel: +91-11-27666156, Fax: +91-11-27662407 Email: [email protected] Nature Precedings : hdl:10101/npre.2010.4330.1 Posted 5 Apr 2010 Running head: Pentylenetetrazole mechanism in Down syndrome 1 Abstract Pentylenetetrazole (PTZ) has recently been found to ameliorate cognitive impairment in rodent models of Down syndrome (DS). The mechanism underlying PTZ’s therapeutic effect is however not clear. Microarray profiling has previously reported differential expression of genes in DS. No mammalian transcriptomic data on PTZ treatment however exists. Nevertheless, a Drosophila model inspired by rodent models of PTZ induced kindling plasticity has recently been described. Microarray profiling has shown PTZ’s downregulatory effect on gene expression in fly heads. In a comparative transcriptomics approach, I have analyzed the available microarray data in order to identify potential mechanism of PTZ action in DS. I find that transcriptomic correlates of chronic PTZ in Drosophila and DS counteract each other. A significant enrichment is observed between PTZ downregulated and DS upregulated genes, and a significant depletion between PTZ downregulated and DS dowwnregulated genes. Further, the common genes in PTZ Nature Precedings : hdl:10101/npre.2010.4330.1 Posted 5 Apr 2010 downregulated and DS upregulated sets show enrichment for MAP kinase pathway. My analysis suggests that downregulation of MAP kinase pathway may mediate therapeutic effect of PTZ in DS. Existing evidence implicating MAP kinase pathway in DS supports this observation. -
571810V1.Full.Pdf
bioRxiv preprint doi: https://doi.org/10.1101/571810; this version posted March 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. TITLE PAGE Title: Alternative Titles: β-Catenin tumour-suppressor activity depends on its ability to promote Pro-N-Cadherin maturation Authors: Antonio Herrera, Anghara Menendez, Blanca Torroba and Sebastian Pons* Affiliation: Instituto de Biología Molecular de Barcelona (CSIC), Parc Científic de Barcelona, Baldiri Reixac 10-12, Barcelona 08028, Spain. Tlf: 34-934031103 Present Affiliation for Blanca Torroba: Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Rd, Oxford OX1 3QX (UK). Correspondence author: Sebastian Pons, Instituto de Biología Molecular de Barcelona, (CSIC), Parc Científic de Barcelona, Baldiri Reixac 10-12, Barcelona 08028, Spain. [email protected] Running Title: β-Catenin promotes N-Cadherin maturation Keywords: Pro-N-Cadherin, β-Catenin, Medulloblastoma, Neuroepithelium, Apico-basal polarity, Adherens Junctions. 1 bioRxiv preprint doi: https://doi.org/10.1101/571810; this version posted March 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. SUMMARY Neural stem cells (NSCs) form a pseudostratified, single-cell layered epithelium with a marked apico-basal polarity. In these cells, β-Catenin associates with classic cadherins in order to form the apical adherens junctions (AJs). We previously reported that oncogenic forms of β-Catenin (sβ-Catenin) maintain neural precursors as progenitors, while also enhancing their polarization and adhesiveness, thereby limiting their malignant potential.