Two Drosophila suppressors of cytokine signaling (SOCS) differentially regulate JAK and EGFR pathway activities.
BACKGROUND
The Janus kinase (JAK) cascade is an essential and well-conserved pathway required to transduce signals for a variety of ligands in both vertebrates and invertebrates. While activation of the pathway is essential to many processes, mutations from mammals and Drosophila demonstrate that regulation is also critical. The SOCS (Suppressor Of Cytokine Signaling) proteins in mammals are regulators of the JAK pathway that participate in a negative feedback loop, as they are transcriptionally activated by JAK signaling. Examination of one Drosophila SOCS homologue, Socs36E, demonstrated that its expression is responsive to JAK pathway activity and it is capable of downregulating JAK signaling, similar to the well characterized mammalian SOCS.


RESULTS
Based on sequence analysis of the Drosophila genome, there are three identifiable SOCS homologues in flies. All three are most similar to mammalian SOCS that have not been extensively characterized: Socs36E is most similar to mammalian SOCS5, while Socs44A and Socs16D are most similar to mammalian SOCS6 and 7. Although Socs44A is capable of repressing JAK activity in some tissues, its expression is not regulated by the pathway. Furthermore, Socs44A can enhance the activity of the EGFR/MAPK signaling cascade, in contrast to Socs36E.


CONCLUSIONS
Two Drosophila SOCS proteins have some overlapping and some distinct capabilities. While Socs36E behaves similarly to the canonical vertebrate SOCS, Socs44A is not part of a JAK pathway negative feedback loop. Nonetheless, both SOCS regulate JAK and EGFR signaling pathways, albeit differently. The non-canonical properties of Socs44A may be representative of the class of less characterized vertebrate SOCS with which it shares greatest similarity.
Rawlings
Jason S
JS
Dept. of Biology, University of Kentucky, 101 Morgan Bldg. Lexington, KY 40506, USA. jrawling@uky.edu <jrawling@uky.edu>
Rennebeck
Gabriela
G
Harrison
Susan M W
SM
Xi
Rongwen
R
Harrison
Douglas A
DA
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D016678:Genome; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D008969:Molecular Sequence Data; D009866:Oogenesis / Q000235:genetics; D010053:Ovary / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D018010:Receptors, Invertebrate Peptide / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D050826:Suppressor of Cytokine Signaling Proteins; D015854:Up-Regulation / Q000502:physiology; D014921:Wings, Animal / Q000196:embryology / Q000201:enzymology
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D018010:Receptors, Invertebrate Peptide; D012097:Repressor Proteins; C502965:SOCS44A protein, Drosophila; C460659:Socs36E protein, Drosophila; D050826:Suppressor of Cytokine Signaling Proteins; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3