Kato H, Fukuda T, Parkison C, McPhie P, Cheng S Y
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1989 Oct;86(20):7861-5. doi: 10.1073/pnas.86.20.7861.
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.
已分离出一个编码人胞质甲状腺激素结合蛋白（p58）的cDNA克隆。发现该人类序列与大鼠丙酮酸激酶（EC 2.7.1.40）亚型M2的序列同源。p58是一种单体，其酶活性约为四聚体丙酮酸激酶M2的5%。四聚体M2不结合3,3',5-三碘-L-甲状腺原氨酸（T3）。p58与T3及其类似物的结合导致其丙酮酸激酶活性受到抑制。T3、L-甲状腺素和D-T3的表观Ki值分别为30 nM、100 nM和2 mM。L-甲状腺原氨酸和3,3',5'-三碘-L-甲状腺原氨酸没有作用。这种活性顺序与报道的T3及其类似物的产热效应相关。p58向四聚体的转化是可逆的，受1,6-二磷酸果糖的控制。该转化受到T3的剂量依赖性抑制。由于丙酮酸激酶是调节细胞ADP、ATP和丙酮酸的关键酶，我们的发现表明p58可能参与介导甲状腺激素诱导的一些细胞代谢效应。
