Open AccessDifferential expression of type I and type II cyclic AMP-dependent protein kinases during cell cycle and cyclic AMP-induced growth arrest.
Author(s) -
Mari K. Haddox,
Bruce E. Magun,
Diane Haddock Russell
Publication year - 1980
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.77.6.3445
Subject(s) - protein kinase a , cyclin dependent kinase 2 , kinase , biology , adenylate kinase , cycloheximide , microbiology and biotechnology , chemistry , biochemistry , enzyme , protein biosynthesis
The activation state of cyclic AMP-dependent protein kinase(s)(ATP:protein phosphotransferase, EC 2.7.1.37) is transiently increased 2-fold as a function of G1 progression in mitotically synchronized Chinese hamster ovary cells. The cellular content of type I kinase increases concomitantly with the increase in general protein, whereas the activity of type II kinase increases as a function of time in G1 to a maximum at the G1/S border. In contrast, in the presence of dibutyryl-cyclic AMP, there is a decrease of type II kinase and a several-fold increase of type I kinase. In proliferating cells, the ratio of type I to type II was 0.37, while in the dibutyryl-cyclic AMP growth-arrested cells it was 3.96. The increase in type II kinase during G1 transition and the increase in type I kinase during dibutyryl-cyclic AMP treatment were dependent on protein synthesis. A similar pattern of type I and type II kinase expression during cell cycle progression occurred in Rat-1 fibroblasts and Rat-1 cells transformed by Rous sarcoma virus. The inclusion of dibuityryl-cyclic AMP in the growth media promoted a marked increase in type I holoenzyme, which was inhibited by cycloheximide, and a decrease in type II kinase. Neither AMP nor sodium butyrate had any effect on cellular kinase levels, whereas 8-bromo-cyclic AMP mimicked the action of dibutyryl-cyclic AMP. Estimation of half-lives for the kinase types showed that there was little turnover of either type during normal G1 progression, rapid turnover of both types as cells exited from mitosis, and selective turnover of type II upon addition of dibutyryl-cyclic AMP.