Journal article

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

Abstract

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..

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Grants

Awarded by National Health and Medical Research Council (NHMRC), Australia


Awarded by NHMRC TRUSS Grant


Awarded by Cancer Council Victoria Grant


Funding Acknowledgements

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.