Paracrine GPR34 activation in salivary gland MALT lymphoma. Salivary gland MALT lymphoma (top) with typical lymphoepithelial lesion (left) highlighted by pan-cytokeratin staining (center) and increased apoptotic bodies (right, arrows). Phospholipase A1 is normally secreted by salivary gland epithelia (center left) and catalyzes generation of lysophosphatidylserine from phosphatidylserine exposed on apoptotic cells (center right). Lysophosphatidylserine binds to GPR34 and activates downstream signaling through the NF-κB, MAPK/JNK and cAMP/PKA pathways. The paracrine stimulation is independent of GPR34 mutational status. Red dots mark the location of the GPR34 mutations investigated by Korona et al, with the Q340X mutation in the C-terminal tail showing the most pronounced effects followed by the D151A mutation. The R84H mutation showed an effect similar to that of the GPR34 wild-type.