FIG. 4.
Current two-step model of PacC proteolytic activation. Details are described in the text. PacC72, PacC53, and PacC27 refer to the 72-kDa full-length, the 53-kDa intermediate, and the 27-kDa processed PacC forms, respectively. The signaling cleavage step requires alkaline pH signaling through the pal pathway and leads to the intermediate, which is committed to the ambient pH-independent processing cleavage step. The processing protease has not yet been identified, but PalB would appear to be the signaling protease recognizing the signaling protease box (shown as an open box). Commitment to processing results from removal of interacting region C, which is also removed by pacCc-truncating mutations. That the signaling cleavage occurs in the cytosol is supported by the nuclear exclusion of its PacC72 substrate and the preferential nuclear localization of its PacC53 product (82). The processing cleavage might be in the cytosol and/or in the nucleus, as indicated by the dotted lines connecting PacC53 and PacC27. pacC is itself an alkali-expressed gene (122).