Figure 5.

Schematic summery of the functional relationship between matriptase and its cognate inhibitors HAI-1 and HAI-2 in B-cell malignancies. The regulations of matriptase expression and plasma membrane translocation by HAI-1 versus HAI-2 are summarized schematically. In the presence of extremely low levels of the HAIs, matriptase can only be synthesized to relatively low levels, most of which remains inside the cells. With a modest increase in HAI expression, matriptase synthesis and translocation to the plasma membrane is significantly increased. The majority of the HAI-2 remains inside the cells in vesicle-like structures. As a consequence, HAI-2 can’t effectively control cell surface matriptase proteolysis. In contrast, the majority of HAI-1 is targeted to the plasma membrane, where HAI-1 can rapidly inhibit active matriptase by forming a stable protease–protease inhibitor complex. As a consequence, along with the increase in HAI-1 expression, the formation of activated matriptase-HAI-1 complex increases and the shedding of free active matriptase decreases proportionally.