It has been proposed that a
cysteine proteinase inhibitor (
CPI) found in the ascitic fluid of
Sarcoma 180 tumor-bearing mice is a kind of
kininogen (Itoh, N., Yokota, S., Takagishi, U., Hatta, A., and Okamaoto, H. (1987)
Cancer Res. 47, 5560-5565). The first 40 NH2-terminal residues and 54 residues of the COOH-terminal sequence, including the
bradykinin moiety of highly purified
ascites CPI, were determined and compared with those of mammalian
low molecular weight kininogens (
LMWK). The significant identity between these amino acid sequences with those of other mammalian LMWKs suggests that
ascites CPI corresponds precisely to mouse
LMWK. This
kininogen has a light chain composed of 43
amino acid residues, which contains a unique Met-Ala-Arg-
bradykinin sequence.
Hydroxyproline, which was recently identified in the
bradykinin sequence of
kininogen from the ascitic fluid of a
cancer patient, was not found in the
kinin moiety of this mouse
kininogen. Among purified glandular
kallikreins from human, hog, rat, and mouse, only mouse submaxillary gland
kallikrein was able to release
bradykinin from this
kininogen. Kinetic studies using a newly synthesized
fluorogenic substrate, N-t-butoxycarbonyl-Met-Ala-Arg-MCA, revealed that mouse
kallikrein hydrolyzes this substrate approximately 80-fold faster than does hog
kallikrein, suggesting that the unique Met-Ala-Arg-
bradykinin sequence is responsible for the varied susceptibility of mouse
kininogen to different
kallikreins.