Thyroid hormones inhibit the Ca2+ calmodulin-induced activation of myosin light chain kinase.
L-Thyroxine (T4) and L-triiodothyronine (T3) specifically, inhibited myosin light chain kinase (MLC-kinase) from various tissues whereas inhibitory effects of T4 and T3 on other protein kinases such as protein kinase C, cAMP-dependent protein kinase, casein kinase I, casein kinase II and calmodulin kinase II were much weaker. T4 was a more potent inhibitor of MLC-kinase than T3. Kinetic studies showed that T4 behaved as a competitive inhibitor of MLC-kinase toward calmodulin (CaM) and that Ki value was 2.5 microM. The activity of the catalytic fragment of MLC-kinase, which is active without CaM, was not inhibited by T4. 125I-T4 gel overlay revealed that CaM did not bind T4 but MLC-kinase had 125I-T4 binding activity. These observations suggest that T4 binds at or near CaM binding domain of MLC-kinase and inhibits CaM-induced activation of MLC-kinase.
Hagiwara
M
M
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Japan.
Mamiya
S
S
Ochiai
M
M
Hidaka
H
H
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D002645:Chickens; D004789:Enzyme Activation; D007700:Kinetics; D009130:Muscle, Smooth / Q000201:enzymology; D009132:Muscles / Q000201:enzymology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D002147:Calmodulin; D013963:Thyroid Hormones; D014284:Triiodothyronine; D011494:Protein Kinases; D009219:Myosin-Light-Chain Kinase; D013974:Thyroxine; D002118:Calcium