DrosophilaSOCS36E negatively regulates JAK/STAT pathway signaling via two separable mechanisms

• DOI: 10.1091/mbc.e13-05-0275
• Publication Date: 2013-07-25T13:24:40Z
• Authors: Wojciech Stec; Oscar Vidal; Martin P. Zeidler
• Keywords: Cullin; STAT2

Conserved from humans to Drosophila, the Janus kinase/signal transducer and activators of transcription (JAK/STAT) signaling cascade is essential for multiple developmental homeostatic processes, with regulatory molecules controlling pathway activity also highly conserved. We characterize Drosophila JAK/STAT regulator SOCS36E show that it functions via two independent mechanisms. First, we Elongin B/C Cullin-5 act SOCS-box reduce specifically in response ligand stimulation--a process involves endocytic trafficking lysosomal degradation Domeless (Dome) receptor. Second, suppresses both stimulated basal an Elongin/Cullin-independent mechanism mediated by N-terminus SOCS36E, which required physical interaction Dome. Although some human SOCS proteins contain N-terminal kinase-inhibitory domains, do not identify such a region propose model wherein blocks access tyrosine residues Our biochemical analysis SOCS-family lower organism highlights fundamental conserved roles played mechanisms signal transduction.