The stimulation by adrenocorticotropin of the phosphorylation of adrenal inhibitor-1: a possible role in steroidogenesis.
Adrenocorticotropin (ACTH) acts via protein kinase A and the putative phosphorylation of a regulatory protein(s). We have examined a role in this process for inhibitor-1 which, following phosphorylation by protein kinase A, inhibits a phosphoprotein phosphatase activity. In the tissues we have examined inhibitor-1 was found primarily in the cytosol (90%) with the rest in the mitochondrial pellet. The highest concentration was in the adrenal cortex. Using adrenal cortex slices, the stimulation of steroidogenesis by ACTH and dibutyryl cAMP is paralleled by a corresponding increase in the phosphorylation of inhibitor-1 and this is not affected by inhibitors of protein synthesis which inhibit the steroidogenic response. The increase in the phosphorylation of inhibitor-1 occurs in the cytosol, while that in the mitochondrial pellet is not affected. Exogenous phosphorylated inhibitor-1, however, was found to inhibit phosphoprotein phosphatase activity in the mitochondrial pellet. The results suggest that the ACTH-induced increase in phosphorylated inhibitor-1 in the cytosol can affect susceptible phosphoprotein phosphatase activity both in the cytosol and the mitochondrial pellet and, hence, the level of phosphorylation of regulatory protein(s) involved in steroidogenesis.
Iyer
R B
RB
Department of Biochemistry, Mount Sinai School of Medicine, New York, NY 10029.
Chauhan
A
A
Koritz
S B
SB
D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D011494:Protein Kinases / Q000502:physiology; D013256:Steroids / Q000378:metabolism*; D013268:Stimulation, Chemical; D013347:Subcellular Fractions / Q000032:analysis; D014018:Tissue Distribution
D013256:Steroids; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D011494:Protein Kinases