Journal article

Regulation of IRAK-1 activation by its C-terminal domain

Thao Nguyen, Dominic De Nardo, Paul Masendycz, John A Hamilton, Glen M Scholz



Macrophages are important mediators of the immune response to infection by virtue of their ability to secrete cytokines that trigger inflammation. Toll-like receptors (TLRs) are largely responsible for meditating the activation of macrophages by pathogens. IRAK-1 is a proximal protein kinase in TLR signalling pathways and hence its activation must be tightly regulated. However, the mechanisms which control the activation of IRAK-1 are poorly understood. IRAK-1 contains a death domain at its N-terminus that mediates its interaction with other death domain containing proteins, a central Ser/Thr kinase domain, and a C-terminal domain that contains binding motifs for TRAF6. We show here that del..

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Funding Acknowledgements

The authors wish to thank Drs. S. Ghosh (Yale University), A. Mansell (Monash University, Australia) and M. Sweet (University of Queensland, Australia) for generously providing plasmids. This work was supported in part by the Cooperative Research Centre for Chronic Inflammatory Diseases and the National Health and Medical Research Council (NHMRC). T.N. was supported by a NHMRC Biomedical (Dora Lush) Postgraduate scholarship, while J.A.H. is supported by a NHMRC Senior Principal Research Fellowship.