Phosphorylation of Human Cytochrome P450c17 by p38α Selectively Increases 17,20 Lyase Activity and Androgen Biosynthesis

摘要: Cytochrome P450c17, a steroidogenic enzyme encoded by the CYP17A1 gene, catalyzes steroid 17α-hydroxylation needed for glucocorticoid synthesis, which may or not be followed 17,20 lyase activity sex synthesis. Whether P450c17 is determined three post-translational mechanisms influencing availability of reducing equivalents donated P450 oxidoreductase (POR). These are increased amounts POR, allosteric action cytochrome b5 to promote POR-P450c17 interaction, and Ser/Thr phosphorylation also appears interaction. The kinase(s) that phosphorylates unknown. In series kinase inhibition experiments, pyridinyl imidazole drugs SB202190 SB203580 inhibited but 17α-hydroxylase in human adrenocortical HCI-H295A cells, suggesting an on p38α p38β. Co-transfection non-steroidogenic COS-1 cells with p38 expression vectors showed p38α, p38β, conferred P450c17. Antiserum co-immunoprecipitated both isoforms; however, knockdown NCI-H295A cells. Bacterially expressed was phosphorylated vitro at non-canonical site, conferring activity. This maximum velocity, Michaelis constant, reaction. fashion confers activity, implying production adrenal androgens (adrenarche) regulated event.