Skip to main content
. Author manuscript; available in PMC: 2019 Mar 6.
Published in final edited form as: Annu Rev Immunol. 2013 Dec 18;32:83–119. doi: 10.1146/annurev-immunol-032713-120249

Figure 3. TLR and RLR signaling in myeloid cells require Ptpn22 for efficient TRAF3 autopolyubiqutination.

Figure 3.

Type 1 interferon-inducing Pattern Recognition receptors (TLR3, 4, 7, 9; MDA-5) engage microbial products in extracellular milieu, endosomes, or cytoplasm of dendritic cells or macrophages(53). Pattern recognition receptor ligation induces lysine-63-linked autoubiquitination of TRAF3. Ptpn22 associates with TRAF3 and promotes TRAF3 K63-linked polyubiquitination in a phosphatase-independent manner (Wang et al, 2013). TRAF3 ubiquitination results in activation of serine-threonine kinases TBK1 and IKKε. Substrates for TBK1/IKKε include transcription factors IRF3 and IRF7; upon phosphorylation, the latter translocate to the nucleus and activate type 1 interferon transcriptional upregulation.