The dominant role of the prosegment of prorenin in determining the rate of activation by acid or trypsin: studies with molecular chimeras.
Human prorenin activation by acid or trypsin is faster than rat prorenin by two orders of magnitude. No plausible mechanism exists to explain the difference. Two chimeric mutant prorenins were produced in CHO cells. A chimera, hPro/rRen, composed of human prorenin prosegment and rat active renin segment, was activated as fast as wild-type human prorenin at pH 3.3 and 25 degrees C or by trypsin (1 microg/ml). The other chimera, rPro/hRen, composed of rat prorenin prosegment and human active renin segment, was activated as slowly as wild-type rat prorenin at pH 3.3 and 25 degrees C or by trypsin (50 microg/ml). These results indicate that the rate of activation of prorenin is predominantly determined by the N-terminal pro-sequence. Plausible mechanisms are discussed.
Suzuki
F
F
Molecular Genetics Research Center, Gifu University, Gifu, 501-1193, Japan. aob3073@cc.gifu-u.ac.jp
Nakagawa
T
T
Kakidachi
H
H
Murakami
K
K
Inagami
T
T
Nakamura
Y
Y
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014357:Trypsin / Q000494:pharmacology
D017931:DNA Primers; D004792:Enzyme Precursors; D011993:Recombinant Fusion Proteins; D014357:Trypsin; D012083:Renin