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SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc

Abstract

We have cloned a novel SOCS gene from Drosophila, socs36E, which is most homologous to the mammalian socs-5 gene. Socs36E is expressed zygotically, predominantly during embryogenesis, in a highly dynamic pattern. In vivo expression of SOCS36E in transgenic flies results in several adult phenotypes. Engrailed-GAL4 directed expression causes loss of the wing anterior cross vein, humeral outgrowths, absence of halteres and eye pigmentation defects. Expression of SOCS36E under apterous-GAL4 control resulted in outstretched wings. Full penetrance of these phenotypes required the presence of the SH2 and SOCS-box domains of SOCS36E. The observed phenotypes were consistent with defects in JAK/STAT or EGF-R signalling and were exacerbated in flies heterozygous for either the d-jak (hopscotch), d-stat (stat92E) or d-egf-r (der) genes. Conversely, inactivating one copy of the d-cbl gene, a negative regulator of the d-EGF-R, partially rescued the wing phenotypes. These genetic interactions imply that SOCS36E can suppress activities of the JAK/STAT and EGF-R signalling pathways in the wing disc and suggest that SOCS36E interacts with multiple pathways in vivo.

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Acknowledgements

We thank Norbert Perrimon for providing the cDNA library, pAct5C and pUASp expression plasmids and Oregon-R (OreR), yw, FM7/hopC111, TM3,Sb/stat1681, apMD544/CyO (apterous (ap)-GAL4), e16e (engrailed (en)-GAL4), dpp-GAL4/CyO, UAS-EGFP, en-GAL4, UAS-EGFP and Act-GAL4/CyO fly stocks. derEC20/CyO and TM3,Ser/d-cbl[F165]FRT80B,e stocks were the generous gift of Dr Trudi Schupbach. We thank Erika Bach for providing the yw; UAS-Hop68/CyO stock. Finally, we thank Hervé Agaisse and other lab colleagues for their constructive comments during the preparation of this manuscript. This work was supported by a National Institutes of Health Grant RO1 HL62434-01 to B Mathey-Prevot. BA Callus is the recipient of an NHMRC Howard Florey Centenary Research Fellowship of Australia.

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Correspondence to Bernard A Callus.

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Callus, B., Mathey-Prevot, B. SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc. Oncogene 21, 4812–4821 (2002). https://doi.org/10.1038/sj.onc.1205618

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