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Database (Oxford). 2014 Feb 25;2014:bau007. doi: 10.1093/database/bau007. Print 2014.

TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling.

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1
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA, Department of Biological Chemistry, Johns Hopkins University School of Medicine, 733 N. Broadway, Maryland, 21205, USA, Department of Oncology, Johns Hopkins University School of Medicine, 733 N. Broadway, Maryland, 21205, USA, Department of Pathology, Johns Hopkins University School of Medicine, 733 N. Broadway, Maryland, 21205, USA, Institute of Bioinformatics, International Technology Park, Bangalore 560066, India, Manipal University, Madhav Nagar, Manipal 576104, India, Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605014, India, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA, Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mailcode L592, Portland, OR 97239, USA and Immunology Program, Benaroya Research Institute at Virginia Mason, 1201 9th Avenue S&C, Seattle, WA 98101, USA.

Abstract

Thymic stromal lymphopoietin (TSLP) is a four-helix bundle cytokine that plays a critical role in the regulation of immune responses and in the differentiation of hematopoietic cells. TSLP signals through a heterodimeric receptor complex consisting of an interleukin-7 receptor α chain and a unique TSLP receptor (TSLPR) [also known as cytokine receptor-like factor 2 (CRLF2)]. Cellular targets of TSLP include dendritic cells, B cells, mast cells, regulatory T (Treg) cells and CD4+ and CD8+ T cells. The TSLP/TSLPR axis can activate multiple signaling transduction pathways including the JAK/STAT pathway and the PI-3 kinase pathway. Aberrant TSLP/TSLPR signaling has been associated with a variety of human diseases including asthma, atopic dermatitis, nasal polyposis, inflammatory bowel disease, eosinophilic eosophagitis and, most recently, acute lymphoblastic leukemia. A centralized resource of the TSLP signaling pathway cataloging signaling events is not yet available. In this study, we present a literature-annotated resource of reactions in the TSLP signaling pathway. This pathway map is publicly available through NetPath (http://www.netpath.org/), an open access signal transduction pathway resource developed previously by our group. This map includes 236 molecules and 252 reactions that are involved in TSLP/TSLPR signaling pathway. We expect that the TSLP signaling pathway map will provide a rich resource to study the biology of this important cytokine as well as to identify novel therapeutic targets for diseases associated with dysregulated TSLP/TSLPR signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_24.

PMID:
24573880
PMCID:
PMC3935308
DOI:
10.1093/database/bau007
[Indexed for MEDLINE]
Free PMC Article
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