Mutations impair the tyrosine phosphatase activity of PTPRD. Expression of the STAT3 protein and of the phosphorylated STAT3 protein (pSTAT3, Y705) in HEK 293 cells transfected with constructs expressing wild-type PTPRD-GFP (WT), mutant PTPRD-GFP, or empty vector (EV). Nontransfected HEK 293T cells (293T ctrl) and OCI-LY8 were used as negative control for PTPRD expression. The HEK 293T cells transfected with a vector containing the wild-type PTPRD tagged with GFP at the C-terminal were used as positive control for PTPRD expression (western blot shows the GFP-tagged full-length PTPRD protein [250 kDa], as well as 2 N-terminal PTPRD protein products [150 kDa and 90 kDa], and a GFP-tagged C-terminal PTPRD product [110 kDa] after cleavage process by a physiologic posttranslational modification called ectodomain shedding⁶⁰ ). Protein lysates were prepared from cell cultures treated with or without 5 or 10 ng/mL human interleukin-6 (IL-6). Relative densitometric values of the phosphorylated STAT3 protein (pSTAT3, Y705) (shown for each band) were normalized against the levels of the internal loading control (α-actin).