Elsevier

Developmental Biology

Volume 288, Issue 2, 15 December 2005, Pages 420-433
Developmental Biology

Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand

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Abstract

The characterisation of ligands that activate the JAK/STAT pathway has the potential to throw light onto a comparatively poorly understood aspect of this important signal transduction cascade. Here, we describe our analysis of the only invertebrate JAK/STAT pathway ligands identified to date, the Drosophila unpaired-like family. We show that upd2 is expressed in a pattern essentially identical to that of upd and demonstrate that the proteins encoded by this region activate JAK/STAT pathway signalling. Mutational analysis demonstrates a mutual semi-redundancy that can be visualised in multiple tissues known to require JAK/STAT signalling. In order to better characterise the in vivo function of these ligands, we developed a reporter based on a natural JAK/STAT pathway responsive enhancer and show that ectopic upd2 expression can effectively activate the JAK/STAT pathway. While both Upd and Upd2 are secreted JAK/STAT pathway agonists, tissue culture assays show that the signal-sequences of Upd and Upd2 confer distinct properties, with Upd associated primarily with the extracellular matrix and Upd2 secreted into the media. The differing biophysical characteristics identified for Upd-like molecules have implications for their function in vivo and adds another aspect to our understanding of cytokine signalling in Drosophila.

Keywords

Unpaired
Domeless
STAT
Cytokine
Janus Kinase
Drosophila melanogaster
Ligand
Auto-regulation

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Current address: Faculty of Life Sciences, University of Manchester, C.1247 Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.