Journal
ONCOGENE
Volume 24, Issue 15, Pages 2503-2511Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1208487
Keywords
hopscotch; janus kinase; proliferation; STAT92E; unpaired
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The JAK/STAT signalling pathway mediates both anti-proliferative 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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