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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Cell Line
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Cloning, Molecular
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DNA-Binding Proteins / antagonists & inhibitors
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Drosophila / embryology*
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Drosophila / genetics
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Drosophila / metabolism*
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Drosophila Proteins / antagonists & inhibitors*
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Drosophila Proteins / genetics
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Drosophila Proteins / physiology*
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ErbB Receptors / antagonists & inhibitors
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Humans
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Janus Kinases
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Mice
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Molecular Sequence Data
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Protein Kinases*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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RNA, Messenger / biosynthesis
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Receptors, Invertebrate Peptide / antagonists & inhibitors
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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STAT Transcription Factors
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Sequence Alignment
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Signal Transduction*
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Suppressor of Cytokine Signaling Proteins
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Trans-Activators / antagonists & inhibitors
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Transcription Factors
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Wings, Animal / anatomy & histology
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Wings, Animal / embryology
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Wings, Animal / metabolism
Substances
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DNA-Binding Proteins
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Drosophila Proteins
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RNA, Messenger
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Receptors, Invertebrate Peptide
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Repressor Proteins
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STAT Transcription Factors
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Socs36E protein, Drosophila
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Stat92E protein, Drosophila
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Suppressor of Cytokine Signaling Proteins
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Trans-Activators
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Transcription Factors
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Protein Kinases
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Egfr protein, Drosophila
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ErbB Receptors
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Protein-Tyrosine Kinases
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Janus Kinases
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hop protein, Drosophila