In vitro activation of bovine adrenal tyrosine hydroxylase by rabbit skeletal muscle actin: evidence for a possible role of cytoskeletal elements as an activator for cytoplasmic enzymes.
Tyrosine hydroxylase prepared from the soluble fraction of bovine adrenal medulla was markedly activated by rabbit skeletal muscle G-actin, and this activation was accompanied by a decrease in the apparent Km of the enzyme for the pterin cofactor. The activating effect of G-actin on the soluble enzyme was still observed in the medium containing a high concentration of salt or excess amounts of proteinase inhibitors. Furthermore, this effect was not affected by either cytochalasin B or DNase I. These results therefore suggest that G-actin interacts with the enzyme molecule at the binding site(s) different from that involved in actin polymerization, and that it causes the activation of the soluble enzyme as a result of an allosteric alteration in the enzyme structure, thus giving rise to the possibility that cytoskeletal elements play an important role in the regulation of catecholamine synthesis as a factor modulating the activity of cytoplasmic tyrosine hydroxylase.
Morita
K
K
Department of Pharmacology, Tokushima University School of Medicine, Japan.
Nakanishi
A
A
Oka
M
M
D000199:Actins / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology; D000313:Adrenal Medulla / Q000201:enzymology*; D000818:Animals; D002417:Cattle; D003571:Cytochalasin B; D003593:Cytoplasm / Q000201:enzymology; D003599:Cytoskeleton / Q000502:physiology; D003850:Deoxyribonuclease I; D004789:Enzyme Activation; D007700:Kinetics; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000494:pharmacology; D011817:Rabbits; D014446:Tyrosine 3-Monooxygenase / Q000302:isolation & purification / Q000378:metabolism*
D000199:Actins; D011480:Protease Inhibitors; D003571:Cytochalasin B; D014446:Tyrosine 3-Monooxygenase; D003850:Deoxyribonuclease I