Figure 1

Structure of matriptase and HAI-1 and proposed life cycle of matriptase. (A) Domain structures of matriptase and HAI-1. The N-terminal cleavage site within the SEA domain and the activation cleavage site within the serine protease domain of matriptase are indicated by arrowheads. Also shown are the four N-glycosylation sites. (B) (1) Matriptase is synthesized on the rough endoplasmic reticulum and is oriented in the membrane as a single-span type II transmembrane protein by an N-terminal signal anchor. (2) The SEA domain of matriptase undergoes an endoproteolytic cleavage after Gly149 within the endoplasmic reticulum or Golgi apparatus. (3) SEA domain-cleaved matriptase associates with HAI-1, (4) which facilitates transport of the protease to the plasma membrane, (5) where it is activated by autocatalytic cleavage after Arg614 within the highly conserved activation cleavage site R-VVGG. (6) Activated matriptase is rapidly inhibited by HAI-1 (7), and (8) the matriptase-HAI-1 complex is shed from the plasma membrane.