Figure 6. Expression of disease-predisposing variant PTPN22-R620W is associated with diminished TLR signaling.
PTPN22-WT (but not PTPN22-R620W), can promote K63-linked autopolyubiquitination of TRAF3 and signaling leading to upregulation of type 1 IFN (left panel). Candidate mechanisms whereby PTPN22-R620W could result in reduced TRAF3 ubiquitination include partial reduction in direct PTPN22 and TRAF3 interaction(58), or diminished recruitment of an as-yet unidentified effector (Effector X) to the complex (R hand panel). Enzymatic activity of PTPN22 is dispensable for promotion of TLR-induced TRAF3 ubiquitination.