Integration of JAK/STAT receptor-ligand trafficking, signalling and gene expression in Drosophila melanogaster cells.

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 in Drosophila melanogaster cells, Domeless. We identify an evolutionarily conserved di-leucine (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, although 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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Moore R,Vogt K,Acosta-Martin AE,Shire P,Zeidler M,Smythe E

doi

10.1242/jcs.246199

subject

Has Abstract

pub_date

2020-10-12 00:00:00

issue

19

eissn

0021-9533

issn

1477-9137

pii

jcs.246199

journal_volume

133

pub_type

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