Granzyme B (GZMB)

Granzymes are serine proteases that are released by cytoplasmic granules within cytotoxic T cells and natural killer cells. Granzyme B is an important mediator of cytotoxic lymphocyte granule-induced death of target cells, accomplishing this through cleavage of Bid and cleavage and activation of caspases as well as direct cleavage of downstream substrates.The serine proteinase GZMB is crucial for the rapid induction of target cell apoptosis by cytotoxic T cells. GZMB enters cells in a perforin-independent manner, predicting the existence of a cell surface receptor(s). Motyka et al. (2000) presented evidence that this receptor is the cation-independent mannose 6-phosphate receptor (CIMPR), also called IGF2R. Inhibition of the GZMB-IGF2R interaction prevented GZMB cell surface binding, uptake, and the induction of apoptosis.