Fisher, K.H. orcid.org/0000-0002-2751-156X, Fragiadaki, M. orcid.org/0000-0002-1587-5577, Pugazhendhi, D. et al. (5 more authors) (2018) A genome-wide RNAi screen identifies MASK as a positive regulator of cytokine receptor stability. Journal of Cell Science, 131. jcs209551. ISSN 0021-9533
Abstract
Cytokine receptors often act via the Janus kinase and signal transducer and activator of transcription (JAK/STAT) pathway to form a signalling cascade that is essential for processes such as haematopoiesis, immune responses and tissue homeostasis. In order to transduce ligand activation, cytokine receptors must dimerise. However, mechanisms regulating their dimerisation are poorly understood. In order to better understand the processes regulating cytokine receptor levels, and their activity and dimerisation, we analysed the highly conserved JAK/STAT pathway in Drosophila, which acts via a single receptor, known as Domeless. We performed a genome-wide RNAi screen in Drosophila cells, identifying MASK as a positive regulator of Domeless dimerisation and protein levels. We show that MASK is able to regulate receptor levels and JAK/STAT signalling both in vitro and in vivo. We also show that its human homologue, ANKHD1, is also able to regulate JAK/STAT signalling and the levels of a subset of pathway receptors in human cells. Taken together, our results identify MASK as a novel regulator of cytokine receptor levels, and suggest functional conservation, which may have implications for human health.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Authors. Published by The Company of Biologists Ltd. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | Ankyrin domain; Cytokine receptors; Dimerisation; JAK/STAT; RNAi |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number SHEFFIELD HOSPITALS CHARITY 171819 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 28 Aug 2018 11:27 |
Last Modified: | 18 Apr 2024 10:09 |
Status: | Published |
Publisher: | Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/jcs.209551 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:135038 |