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Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

Abstract

The JAK/STAT signalling pathway mediates both antiproliferative responses following interferon stimulation and cellular proliferation in response to cytokines such as interleukins and growth factors. Central to these responses are the seven vertebrate STAT molecules, misregulation of which is implicated in a variety of malignancies. We have investigated the proliferative role of the single Drosophila STAT92E, part of the evolutionarily conserved JAK/STAT cascade. During second instar larval wing disc development pathway activity is both necessary and sufficient to promote proliferation of this epithelial cell type. However by later stages, endogenous STAT92E is stimulated by a noncannonical mechanism to exert pronounced antiproliferative effects. Ectopic canonical activation is sufficient to further decrease proliferation and leads to the premature arrest of cells in the G2 phase of the cell cycle. The single STAT92E present in Drosophila therefore mediates both proproliferative functions analogous to vertebrate interleukin-stimulated STAT3 and antiproliferative functions analogous to interferon-stimulated STAT1. Pro- and antiproliferative roles therefore represent ancestral activities conserved through evolution and subsequently assigned to distinct molecules.

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Acknowledgements

We thank Steven Brown, Ho-Ryun Chung, Wendy Gerber, Sabine Häder, Alf Herzig, Herbert Jäckle, Ralf Pflanz, Iris Plischke and Susan Smith for valuable assistance during this project. Fly stocks and reagents were kindly supplied by the Bloomington Stock Centre, Steven Hou, David Strutt, Christian Lehner, Norbert Perrimon and Ulrich Schäfer. MPZ is supported by a DFG Emmy Noether fellowship, JC-GH received funding from the Royal Society and the Welcome Trust TM is funded by a Max Planck Society pre-doctoral fellowship.

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Correspondence to Martin P Zeidler.

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Mukherjee, T., Hombría, JG. & Zeidler, M. Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation. Oncogene 24, 2503–2511 (2005). https://doi.org/10.1038/sj.onc.1208487

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Keywords

  • Hopscotch
  • Janus kinase
  • proliferation
  • STAT92E
  • unpaired

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