Structure and Functional Characterization of the Conserved JAK Interaction Region in the Intrinsically Disordered N-Terminus of SOCS5
Indu R Chandrashekaran, Biswaranjan Mohanty, Edmond M Linossi, Laura F Dagley, Eleanor WW Leung, James M Murphy, Jeffrey J Babon, Sandra E Nicholson, Raymond S Norton
BIOCHEMISTRY | AMER CHEMICAL SOC | Published : 2015
SOCS5 can negatively regulate both JAK/STAT and EGF-receptor pathways and has therefore been implicated in regulating both the immune response and tumorigenesis. Understanding the molecular basis for SOCS5 activity may reveal novel ways to target key components of these signaling pathways. The N-terminal region of SOCS5 coordinates critical protein interactions involved in inhibition of JAK/STAT signaling, and a conserved region within the N-terminus of SOCS5 mediates direct binding to the JAK kinase domain. Here we have characterized the solution conformation of this conserved JAK interaction region (JIR) within the largely disordered N-terminus of SOCS5. Using nuclear magnetic resonance (N..View full abstract
Awarded by National Health and Medical Research Council (NHMRC), Australia
Awarded by NHMRC TRUSS Grant
Awarded by Cancer Council Victoria Grant
This work was supported in part by the National Health and Medical Research Council (NHMRC), Australia (Program Grant 1016647), as well as an NHMRC TRUSS Grant 361646, a Cancer Council Victoria Grant 1065180 and a Victorian State Government Operational Infrastructure Scheme grant. E.M.L was supported by an Australian Postgraduate Award. R.S.N. acknowledges fellowship support from the NHMRC. J.M.M. and J.J.B acknowledge fellowship support from the Australian Research Council.