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A potent vasoactive peptide, bradykinin, is liberated from two distinct kininogens designated low molecular weight (LMW) and high molecular weight (HMW) kininogens. We have recently cloned and sequenced cDNAs for bovine LMW prekininogens and indicated that LMW prekininogens are encoded by two very similar but distinct mRNAs. This study concerns the structural basis for the relationship between HMW and LMW prekininogen mRNAs by examination of cDNA clones for bovine HMW prekininogens and a genomic clone. Two types of cDNAs for HMW prekininogens have been identified. The deduced sequences of these two mRNAs are identical with those of two LMW prekininogen mRNAs up to the regions preceding the sequences specifying the divergent C-terminal regions of HMW and LMW kininogens, with one-to-one correspondence. In genomic DNA, the sequence precisely corresponding to the divergent 3'-terminal region of LMW prekininogen mRNA is located after 87 nucleotides downstream from the sequence specifying the 3'-untranslated region of HMW prekininogen mRNA. Based on these findings, we conclude that HMW and LMW prekininogen mRNAs are transcribed from the same gene.
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