title: Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand.
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.
authors.affiliation: Centro Andaluz de Biología del Desarrollo, CSIC/Universidad Pablo de Olavide, Carretera de Utrera, Km 1, 41013 Seville, Spain. jcashom@upo.es
authors.forename: James Castelli-Gair
authors.initials: JC
authors.lastname: Hombría
authors.forename: Stephen
authors.initials: S
authors.lastname: Brown
authors.forename: Sabine
authors.initials: S
authors.lastname: Häder
authors.forename: Martin P
authors.initials: MP
authors.lastname: Zeidler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005109:Extracellular Matrix / Q000378:metabolism; D053612:Janus Kinases; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D050791:STAT Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014960:X Chromosome / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; D050791:STAT Transcription Factors; D014157:Transcription Factors; C508880:Upd2 protein, Drosophila; C115570:upd1 protein, Drosophila; D011505:Protein-Tyrosine Kinases; D053612:Janus Kinases; C085845:hop protein, Drosophila