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The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters.
Open accessAbstract
cDNA clones for rat R-type pyruvate kinase and a genomic clone encoding both L- and R-type isozyme mRNAs were isolated. Their sequences were compared with that of the L-type isozyme cDNA to determine the sequences of mRNA and protein of the R-type isozyme and the organizations of the L- and R-type genes. Results showed that the R-type isozyme mRNA had an identical nucleotide sequence to that of the L-type except in the 5'-terminal region including the coding sequence and the length of the 3'-untranslated region. The sequence upstream of the 5th coding residue of the L-type was replaced by a 98-nucleotide coding sequence plus a 5'-untranslated region in the R-type isozyme. Therefore, the R-type subunit consists of 574 amino acids, which is 31 residues longer than the L-type at the amino terminus. The pyruvate kinase L gene is present as a single copy per haploid genome and is composed of 12 exons and 11 introns with a length of about 9.3 kilobase pairs. The first (exon R) and second (exon L) exons encode the 5'-terminal sequences specific for the R- and L-types, respectively. The remaining downstream exons encode a sequence common to both isozymes. The last exon contains the entire 3'-untranslated region, including several putative polyadenylation signals. Alternative use of these signals is reported to be responsible for generation of multiple mRNA species for the L-type, whereas the R-type uses only the first signal. The cap site is mapped 16 nucleotides upstream from the translation initiation site for the L-type, whereas multiple cap sites were suggested for the R-type. The canonical promoter of the TATA box was identified in the upstream sequence of exon L, but not in that of exon R. Instead, the 5'-flanking region of exon R contained another promoter sequence of the CAT box. Thus, we conclude that the L- and R-type isozymes of pyruvate kinase are produced from a single gene by use of different promoters.
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Cited by
Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells
Mazurek, S. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.02.005 · Cited by 694
The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate
Jurica, M. S., Mesecar, A., Heath, P. J., Shi, W., Nowak, T., & Stoddard, B. L. (1998) · Structure · doi:10.1016/s0969-2126(98)00021-5 · Cited by 426
Clower, C. V., Chatterjee, D., Wang, Z., Cantley, L. C., Vander Heiden, M. G., & Krainer, A. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914845107 · Cited by 424
Human M2-type pyruvate kinase: cDNA cloning, chromosomal assignment and expression in hepatoma
Kenzaburo, T., Yoshida, M. C., Hitoshi, S., Keiji, M., Tamio, N., Takehiko, T., Hisaichi, F., & Shiro, M. (1988) · Gene · doi:10.1016/0378-1119(88)90515-x · Cited by 63
Metadata
- Authors
- Noguchi, T., Yamada, K., Inoue, H., Matsuda, T., & Tanaka, T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1987-10
- Volume
- 262
- Issue
- 29
- Pages
- 14366-14371
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1605420823
- Cited by
- 333
- References
- 0
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
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