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

Oncogene. 2002 Jul 18;21(31):4812-21. doi: 10.1038/sj.onc.1205618.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Cloning, Molecular
  • DNA-Binding Proteins / antagonists & inhibitors
  • Drosophila / embryology*
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / antagonists & inhibitors*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • ErbB Receptors / antagonists & inhibitors
  • Humans
  • Janus Kinases
  • Mice
  • Molecular Sequence Data
  • Protein Kinases*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • RNA, Messenger / biosynthesis
  • Receptors, Invertebrate Peptide / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • STAT Transcription Factors
  • Sequence Alignment
  • Signal Transduction*
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators / antagonists & inhibitors
  • Transcription Factors
  • Wings, Animal / anatomy & histology
  • Wings, Animal / embryology
  • Wings, Animal / metabolism

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • RNA, Messenger
  • Receptors, Invertebrate Peptide
  • Repressor Proteins
  • STAT Transcription Factors
  • Socs36E protein, Drosophila
  • Stat92E protein, Drosophila
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators
  • Transcription Factors
  • Protein Kinases
  • Egfr protein, Drosophila
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Janus Kinases
  • hop protein, Drosophila