Moore, R., Vogt, K., Acosta-Martin, A. et al. (3 more authors) (2020) Integration of JAK/STAT receptor/ligand trafficking, signalling and gene expression in Drosophila melanogaster cells. Journal of Cell Science, 133. jcs246199. ISSN 0021-9533
Abstract
The JAK/STAT pathway is an essential signalling cascade required for multiple processes during development and for adult homeostasis. A key question in understanding this pathway is how it is regulated in different cell contexts. Here we have examined how endocytic processing contributes to signalling by the single cytokine receptor, Domeless, in Drosophila melanogaster cells. We identify an evolutionarily conserved di-Leu motif that is required for Domeless internalisation and show that endocytosis is required for activation of a subset of Domeless targets. Our data indicate that endocytosis both qualitatively and quantitatively regulates Domeless signalling. STAT92E, the single STAT transcription factor in Drosophila, appears to be the target of endocytic regulation and our studies show that phosphorylation of STAT92E on Tyr704, while necessary, is not always sufficient for target transcription. Finally, we identify a conserved residue, Thr702, which is essential for Tyr704 phosphorylation. Taken together, our findings identify previously unknown aspects of JAK/STAT pathway regulation likely to play key roles in the spatial and temporal regulation of signalling in vivo.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020. Published by The Company of Biologists Ltd. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | Drosophila, JAK/STAT, endocytosis, signalling; Drosophila; JAK/STAT; endocytosis; signalling |
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) |
Funding Information: | Funder Grant number CANCER RESEARCH UK C12332/A10681 MEDICAL RESEARCH COUNCIL MR/K015753/1 CANCER RESEARCH UK C12332/A10681 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 27 Oct 2020 15:46 |
Last Modified: | 12 Oct 2021 00:38 |
Status: | Published |
Publisher: | Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/jcs.246199 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167289 |