SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc.
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.
Callus
Bernard A
BA
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts, MA 02115, USA. b.callus@garvan.org.au
Mathey-Prevot
Bernard
B
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D053612:Janus Kinases; D051379:Mice; D008969:Molecular Sequence Data; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D018010:Receptors, Invertebrate Peptide / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D050791:STAT Transcription Factors; D016415:Sequence Alignment; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000037:antagonists & inhibitors; D014157:Transcription Factors; D014921:Wings, Animal / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D018010:Receptors, Invertebrate Peptide; D012097:Repressor Proteins; D050791:STAT Transcription Factors; C460659:Socs36E protein, Drosophila; C105675:Stat92E protein, Drosophila; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D053612:Janus Kinases; C085845:hop protein, Drosophila