Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase.
A cDNA clone encoding a human cytosolic thyroid hormone-binding protein (p58) has been isolated. The human sequence was found to be homologous to that of rat pyruvate kinase (EC 2.7.1.40) subtype M2. p58 is a monomer that has approximately 5% the enzymatic activity of the tetrameric pyruvate kinase M2. The tetrameric M2 does not bind 3,3',5-triiodo-L-thyronine (T3). Binding of p58 to T3 and its analogs resulted in the inhibition of its pyruvate kinase activity. The apparent Ki values of T3, L-thyroxine, and D-T3 are 30 nM, 100 nM, and 2 mM, respectively. L-Thyronine and 3,3',5'-triiodo-L-thyronine had no effect. This order of activity correlates with the thermogenic effects reported for T3 and its analogs. Conversion of p58 to the tetramer is reversible and is under the control of fructose 1,6-bisphosphate. The conversion is inhibited by T3 in a dose-dependent manner. Since pyruvate kinase is a key enzyme in regulating cellular ADP, ATP, and pyruvate, our findings suggest that p58 may be involved in mediating some of the cellular metabolic effects induced by thyroid hormones.
Kato
H
H
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Fukuda
T
T
Parkison
C
C
McPhie
P
P
Cheng
S Y
SY
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003488:Cyanogen Bromide; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010446:Peptide Fragments / Q000302:isolation & purification; D014176:Protein Biosynthesis; D011770:Pyruvate Kinase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013963:Thyroid Hormones; D014158:Transcription, Genetic; D000097810:Thyroid Hormone-Binding Proteins
D002352:Carrier Proteins; D003488:Cyanogen Bromide; D004247:DNA; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011770:Pyruvate Kinase; D012333:RNA, Messenger; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins