Schematic representation of the mechanism through which PTPN22 blocks proapoptotic and enhances antiapoptotic BCR signals. PTPN22 prevents LYN activation by dephosphorylating the activating Y397 residue. This results in impaired activation of downstream signaling pathways, including pathways that transduce the proapoptotic BCR signal. However, inactivation of LYN by PTPN22 also prevents recruitment and activation of SHIP, which is a key negative regulator of the PI3K/AKT pathway. In the absence of SHIP, AKT continues to be activated by phosphatidylinositol 3,4,5-trisphosphate (PIP₃), resulting in a net increase in AKT activity despite the overall attenuation of the BCR signal. Tyrosine residues that are directly phosphorylated by LYN are indicated by “P” in the pentagon.