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. 1988 Dec 1;256(2):447–452. doi: 10.1042/bj2560447

The amounts of rat liver cyclic AMP-dependent protein kinase I and II are differentially regulated by diet.

R Ekanger 1, O K Vintermyr 1, S O Døskeland 1
PMCID: PMC1135430  PMID: 2851990

Abstract

1. The fluctuations in rat hepatocyte volume and protein content in response to dietary perturbations (starvation, protein restriction, refeeding) were accompanied by corresponding fluctuations in the amount of the regulatory (R) and catalytic (C) subunits of cyclic AMP-dependent protein kinase. Thus the intracellular concentration of this key enzyme was adjusted to be near constant. 2. The adjustment of cellular R was accomplished almost exclusively by regulating cytosolic RI (R subunit of type I kinase). The preferential down-regulation of cytosolic RI in response to starvation/protein restriction indicates that particulate RI and cytosolic as well as particulate RII are more resistant to breakdown during general catabolism in the hepatocyte. 3. The diet-induced fluctuations of kinase subunits were uniformly distributed in all populations of parenchymatous hepatocytes, regardless of their size and density. It is thus possible to isolate hepatocytes with uniformly altered RI/RII ratio from livers of rats with different feeding regimens. 4. The binding of endogenous cyclic AMP to RI and RII was similar in livers with high RI/RII ratio (fed rats) and low RI/RII ratio (fasted rats) as well as in hepatocytes isolated from fasted rats. Under the conditions of the experiment (short-term stimulation by glucagon), therefore, neither the dietary state nor the RI/RII ratio seemed to affect the apparent affinity of the isoreceptors for cyclic AMP. However, RI appeared to show a slightly higher co-operativity of intracellular cyclic AMP binding than did RII in all states.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  2. Butley M. S., Malkinson A. M. Co-elution of type I and type II cAMP-dependent protein kinase holoenzymes in high salt fractions from DEAE-cellulose. J Biol Chem. 1984 May 10;259(9):6001–6007. [PubMed] [Google Scholar]
  3. Chan T. M., Steiner K. E., Exton J. H. Effects of adrenalectomy on hormone action on hepatic glucose metabolism. Impaired glucagon activation of glycogen phosphorylase in hepatocytes from adrenalectomized rats. J Biol Chem. 1979 Nov 25;254(22):11374–11378. [PubMed] [Google Scholar]
  4. Christoffersen T., Refsnes M., Brønstad G. O., Ostby E., Huse J., Haffner F., Sand T. E., Hunt N. H., Sonne O. Changes in hormone responsiveness and cyclic AMP metabolism in rat hepatocytes during primary culture and effects of supplementing the medium with insulin and dexamethasone. Eur J Biochem. 1984 Jan 16;138(2):217–226. doi: 10.1111/j.1432-1033.1984.tb07904.x. [DOI] [PubMed] [Google Scholar]
  5. Constantinou A. I., Squinto S. P., Jungmann R. A. The phosphoform of the regulatory subunit RII of cyclic AMP-dependent protein kinase possesses intrinsic topoisomerase activity. Cell. 1985 Sep;42(2):429–437. doi: 10.1016/0092-8674(85)90100-x. [DOI] [PubMed] [Google Scholar]
  6. Corbin J. D., Keely S. L., Park C. R. The distribution and dissociation of cyclic adenosine 3':5'-monophosphate-dependent protein kinases in adipose, cardiac, and other tissues. J Biol Chem. 1975 Jan 10;250(1):218–225. [PubMed] [Google Scholar]
  7. Corbin J. D., Sugden P. H., Lincoln T. M., Keely S. L. Compartmentalization of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in heart tissue. J Biol Chem. 1977 Jun 10;252(11):3854–3861. [PubMed] [Google Scholar]
  8. Doskeland S. O., Kvinnsland S., Ueland P. M. Protein kinases activated by cAMP in the genital tract of spayed mice treated with oestradiol-17beta. J Reprod Fertil. 1975 Aug;44(2):207–216. doi: 10.1530/jrf.0.0440207. [DOI] [PubMed] [Google Scholar]
  9. Døskeland S. O., Kvinnsland S. Measurement of adenylate cyclase activity by competitive binding to the free regulatory moiety of protein kinase I. Int J Biochem. 1980;11(3-4):305–311. doi: 10.1016/0020-711x(80)90234-7. [DOI] [PubMed] [Google Scholar]
  10. Edelman A. M., Blumenthal D. K., Krebs E. G. Protein serine/threonine kinases. Annu Rev Biochem. 1987;56:567–613. doi: 10.1146/annurev.bi.56.070187.003031. [DOI] [PubMed] [Google Scholar]
  11. Ekanger R., Døskeland S. O. Use of antibody-sepharose columns to study hormonal activation of cAMP-dependent protein kinase isozymes. Methods Enzymol. 1988;159:97–104. doi: 10.1016/0076-6879(88)59011-0. [DOI] [PubMed] [Google Scholar]
  12. Ekanger R., Sand T. E., Ogreid D., Christoffersen T., Døskeland S. O. The separate estimation of cAMP intracellularly bound to the regulatory subunits of protein kinase I and II in glucagon-stimulated rat hepatocytes. J Biol Chem. 1985 Mar 25;260(6):3393–3401. [PubMed] [Google Scholar]
  13. Fisher M. J., Pogson C. I. Phenylalanine hydroxylase in liver cells. Correlation of glucagon-stimulated enzyme phosphorylation with expressed activity. Biochem J. 1984 Apr 1;219(1):79–85. doi: 10.1042/bj2190079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fuller D. J., Byus C. V., Russell D. H. Specific regulation by steroid hormones of the amount of type I cyclic AMP-dependent protein kinase holoenzyme. Proc Natl Acad Sci U S A. 1978 Jan;75(1):223–227. doi: 10.1073/pnas.75.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. HARRISON G. Arrhythmia during kemithal anaesthesia. Br J Anaesth. 1953 Jul;25(3):204–211. doi: 10.1093/bja/25.3.204. [DOI] [PubMed] [Google Scholar]
  16. Hofmann F., Beavo J. A., Bechtel P. J., Krebs E. G. Comparison of adenosine 3':5'-monophosphate-dependent protein kinases from rabbit skeletal and bovine heart muscle. J Biol Chem. 1975 Oct 10;250(19):7795–7801. [PubMed] [Google Scholar]
  17. Hutson N. J., Mortimore G. E. Suppression of cytoplasmic protein uptake by lysosomes as the mechanism of protein regain in livers of starved-refed mice. J Biol Chem. 1982 Aug 25;257(16):9548–9554. [PubMed] [Google Scholar]
  18. Jahnsen T., Hedin L., Kidd V. J., Beattie W. G., Lohmann S. M., Walter U., Durica J., Schulz T. Z., Schiltz E., Browner M. Molecular cloning, cDNA structure, and regulation of the regulatory subunit of type II cAMP-dependent protein kinase from rat ovarian granulosa cells. J Biol Chem. 1986 Sep 15;261(26):12352–12361. [PubMed] [Google Scholar]
  19. Knight B. L., Skala J. P. Protein kinases in brown adipose tissue of developing rats. Electrophoretic separation and assay of soluble protein kinases on polyacrylamide gels and a study of their properties and changes during development. J Biol Chem. 1977 Aug 10;252(15):5356–5362. [PubMed] [Google Scholar]
  20. Kumon A., Nishiyama K., Yamamura H., Nishizuka Y. Multiplicity of adenosine 3',5'-monophosphate-dependent protein kinases from rat liver and mode of action of nucleoside 3',5'-monophosphate. J Biol Chem. 1972 Jun 25;247(12):3726–3735. [PubMed] [Google Scholar]
  21. Malkinson A. M., Beer D. S., Wehner J. M., Sheppard J. R. Elution of the regulatory subunit of cAMP-dependent protein kinase Type I isozyme derived from epididymal fat within the type II isozyme chromatographic peak. Biochem Biophys Res Commun. 1983 Apr 15;112(1):214–220. doi: 10.1016/0006-291x(83)91818-1. [DOI] [PubMed] [Google Scholar]
  22. McClung J. K., Kletzien R. F. The effect of nutritional status and of glucocorticoid treatment on the protein kinase isozyme pattern of liver parenchymal cells. Biochim Biophys Acta. 1981 Sep 4;676(3):300–306. doi: 10.1016/0304-4165(81)90163-x. [DOI] [PubMed] [Google Scholar]
  23. Miyazaki K., Miyamoto E., Maeyama M., Uchida M. Specific regulation by steroid hormones of protein kinases in the endometrium. 1. Alteration by estrogen and progesterone in levels of protein kinases in rabbit endometrium. Eur J Biochem. 1980 Mar;104(2):535–542. doi: 10.1111/j.1432-1033.1980.tb04456.x. [DOI] [PubMed] [Google Scholar]
  24. Mortimore G. E., Pösö A. R. The lysosomal pathway of intracellular proteolysis in liver: regulation by amino acids. Adv Enzyme Regul. 1986;25:257–276. doi: 10.1016/0065-2571(86)90018-x. [DOI] [PubMed] [Google Scholar]
  25. Patterson M. K., Jr Measurement of growth and viability of cells in culture. Methods Enzymol. 1979;58:141–152. doi: 10.1016/s0076-6879(79)58132-4. [DOI] [PubMed] [Google Scholar]
  26. Roskoski R., Jr Assays of protein kinase. Methods Enzymol. 1983;99:3–6. doi: 10.1016/0076-6879(83)99034-1. [DOI] [PubMed] [Google Scholar]
  27. Rubin C. S., Erlichman J., Rosen O. M. Cyclic adenosine 3',5'-monophosphate-dependent protein kinase of human erythrocyte membranes. J Biol Chem. 1972 Oct 10;247(19):6135–6139. [PubMed] [Google Scholar]
  28. Russell D. H. Type I cyclic AMP-dependent protein kinase as a positive effector of growth. Adv Cyclic Nucleotide Res. 1978;9:493–506. [PubMed] [Google Scholar]
  29. Schwoch G. Differential activation of type-I and type-II adenosine 3':5'-cyclic monophosphate-dependent protein kinases in liver of glucagon-treated rats. Biochem J. 1978 Mar 15;170(3):469–477. doi: 10.1042/bj1700469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Scott J. D., Glaccum M. B., Zoller M. J., Uhler M. D., Helfman D. M., McKnight G. S., Krebs E. G. The molecular cloning of a type II regulatory subunit of the cAMP-dependent protein kinase from rat skeletal muscle and mouse brain. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5192–5196. doi: 10.1073/pnas.84.15.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Seglen P. O. Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:29–83. doi: 10.1016/s0091-679x(08)61797-5. [DOI] [PubMed] [Google Scholar]
  32. Sikorska M., Whitfield J. F., Walker P. R. The regulatory and catalytic subunits of cAMP-dependent protein kinases are associated with transcriptionally active chromatin during changes in gene expression. J Biol Chem. 1988 Feb 25;263(6):3005–3011. [PubMed] [Google Scholar]
  33. Sommarin M., Jergil B. Protein kinases of rat liver endoplasmic reticulum. Solubilisation, partial characterisation and comparison with protein kinases of rat liver cytosol. Eur J Biochem. 1978 Jul 17;88(1):49–60. doi: 10.1111/j.1432-1033.1978.tb12421.x. [DOI] [PubMed] [Google Scholar]
  34. Stein J. C., Rubin C. S. Isolation and sequence of a tryptic peptide containing the autophosphorylation site of the regulatory subunit of bovine brain protein kinase II. J Biol Chem. 1985 Sep 15;260(20):10991–10995. [PubMed] [Google Scholar]
  35. Titani K., Sasagawa T., Ericsson L. H., Kumar S., Smith S. B., Krebs E. G., Walsh K. A. Amino acid sequence of the regulatory subunit of bovine type I adenosine cyclic 3',5'-phosphate dependent protein kinase. Biochemistry. 1984 Aug 28;23(18):4193–4199. doi: 10.1021/bi00313a028. [DOI] [PubMed] [Google Scholar]
  36. Uhal B. D., Roehrig K. L. Effect of dietary state on hepatocyte size. Biosci Rep. 1982 Dec;2(12):1003–1007. doi: 10.1007/BF01122168. [DOI] [PubMed] [Google Scholar]
  37. Uhler M. D., Carmichael D. F., Lee D. C., Chrivia J. C., Krebs E. G., McKnight G. S. Isolation of cDNA clones coding for the catalytic subunit of mouse cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1300–1304. doi: 10.1073/pnas.83.5.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vintermyr O. K., Døskeland S. O. Cell cycle parameters of adult rat hepatocytes in a defined medium. A note on the timing of nucleolar DNA replication. J Cell Physiol. 1987 Jul;132(1):12–21. doi: 10.1002/jcp.1041320103. [DOI] [PubMed] [Google Scholar]
  39. Walter U., Kanof P., Schulman H., Greengard P. Adenosine 3':5'-monophosphate receptor proteins in mammalian brain. J Biol Chem. 1978 Sep 10;253(17):6275–6280. [PubMed] [Google Scholar]
  40. Weber W., Hilz H. cAMP-dependent protein kinases I and II: divergent turnover of subunits. Biochemistry. 1986 Sep 23;25(19):5661–5667. doi: 10.1021/bi00367a047. [DOI] [PubMed] [Google Scholar]
  41. Weldon S. L., Mumby M. C., Taylor S. S. The regulatory subunit of neural cAMP-dependent protein kinase II represents a unique gene product. J Biol Chem. 1985 May 25;260(10):6440–6448. [PubMed] [Google Scholar]
  42. Wittmaack F. M., Weber W., Hilz H. Isoenzymes of cAMP-dependent protein kinase in developing rat liver and in malignant hepatic tissues. Eur J Biochem. 1983 Jan 1;129(3):669–674. doi: 10.1111/j.1432-1033.1983.tb07101.x. [DOI] [PubMed] [Google Scholar]

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