1,25-dihydroxyvitamin D3 alters the effect of cAMP in thyroid cells by increasing the regulatory subunit type II beta of the cAMP-dependent protein kinase

• Published in: The Journal of biological chemistry Vol. 269; no. 51; pp. 32233 - 32238
• Main Authors: Berg, J P, Ree, A H, Sandvik, J A, Taskén, K, Landmark, B F, Torjesen, P A, Haug, E
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 23-12-1994
• Subjects: Animals; Blotting, Western; Calcitriol - pharmacology; Cells, Cultured; Chromatography, Ion Exchange; Cyclic AMP - analogs & derivatives; Cyclic AMP - pharmacology; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; Cyclic AMP-Dependent Protein Kinase Type II; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Drug Interactions; Enzyme Activation; Isoenzymes - genetics; Isoenzymes - metabolism; Rats; RNA, Messenger - genetics; RNA, Messenger - metabolism; Thionucleotides - pharmacology; Thyroid Gland - cytology; Thyroid Gland - drug effects; Thyroid Gland - enzymology; Thyroid Gland - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)31626-0

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) attenuates the stimulatory effects of cAMP on proliferation and iodide uptake in rat
thyroid FRTL-5 cells. This study examines the effects of 1,25-(OH)2D3 on the cAMP-dependent protein kinase (PKA). Cytosol
proteins separated by anion exchange chromatography showed increased [3H]cAMP binding activity as well as increased kinase
activity in the fractions containing PKA type II in 1,25-(OH)2D3 (10 nM)-treated cells compared to the control cells. Western
blot analysis of 1,25-(OH)2D3-treated cells revealed a 4-fold increase in the cytosolic amount of the PKA regulatory subunit
RII beta, whereas no changes were detected in the regulatory subunits RI alpha and RII alpha or the catalytic (C) subunit.
Northern blot analyses showed a similar increase in RII beta mRNA in cells treated for 12 h with 1,25-(OH)2D3 (10 nM), and
RII beta mRNA increased further to 10-fold above control cell level after 96 h of incubation. Iodide uptake was synergistically
stimulated with both PKAI- and PKAII-directed pairs of cAMP analogs. The PKAI synergism was, however, inhibited by 1,25-(OH)2D3
treatment of the cells, whereas the PKAII synergism was unaffected. In conclusion, 1,25-(OH)2D3 attenuates both PKAI formation
and PKAI-stimulated iodide uptake in rat thyroid FRTL-5 cells by increasing the level of RII beta without altering the other
PKA subunit levels.