Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1973 May;70(5):1432–1436. doi: 10.1073/pnas.70.5.1432

Pleiotypic Control by Adenosine 3′:5′-Cyclic Monophosphate: A Model for Growth Control in Animal Cells

Raphaël Kram 1, Pierre Mamont 1, Gordon M Tomkins 1
PMCID: PMC433513  PMID: 4351178

Abstract

The effects of serum deprivation on several general cellular biochemical processes (“pleiotypic response”) related to the growth of normal fibroblasts can be mimicked by treatment of these cells with prostaglandin E1 in the presence of serum. N6,O2′-Dibutyryl adenosine 3′:5′-cyclic monophosphate and theophylline inhibit the membrane transport processes without much effect on other pleiotypic reactions such as overall protein and RNA synthesis and protein degradation. The amount of intracellular cyclic AMP increases during serum starvation and returns to the initial concentration in unstarved cells when growth is initiated again upon addition of serum. Fibroblasts transformed by simian virus 40 have a lower cyclic AMP content than their untransformed parents. Serum deprivation neither increases cyclic AMP content nor significantly affects the pleiotypic reactions in transformed cells. Cycloheximide causes a decrease in cyclic AMP content of normal fibroblasts coincidentally with the ability of this inhibitor to stimulate uridine transport and slow protein degradation in cells deprived of serum.

Keywords: prostaglandin, membrane transport, macromolecular synthesis and degradation

Full text

PDF
1432

Selected References

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

  1. Bonner J. T. Induction of stalk cell differentiation by cyclic AMP in the cellular slime mold Dictyostelium discoideum. Proc Natl Acad Sci U S A. 1970 Jan;65(1):110–113. doi: 10.1073/pnas.65.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cashel M., Gallant J. Two compounds implicated in the function of the RC gene of Escherichia coli. Nature. 1969 Mar 1;221(5183):838–841. doi: 10.1038/221838a0. [DOI] [PubMed] [Google Scholar]
  3. Channing C. P., Seymour J. F. Effects of dibutryl cyclic-3',5'-AMP and other agents upon luteinization of porcine granulosa cells in culture. Endocrinology. 1970 Jul;87(1):165–169. doi: 10.1210/endo-87-1-165. [DOI] [PubMed] [Google Scholar]
  4. Chen S. T., Tchen T. T. Induction of melanocytogenesis in explants of Curassius auratus L the xanthic goldfish by dibutyryl-cAMP. Biochem Biophys Res Commun. 1970 Nov 25;41(4):964–966. doi: 10.1016/0006-291x(70)90178-6. [DOI] [PubMed] [Google Scholar]
  5. D'Armiento M., Johnson G. S., Pastan I. Regulation of adenosine 3',5'-cyclic monophosphate phosphodiesterase activity in fibroblasts by intracellular concentrations of cyclic adenosine monophosphate (3T3-dibutyryl cyclic AMP-SV40-transformed cells-michaelis constants-L cells-prostaglandin E 1 ). Proc Natl Acad Sci U S A. 1972 Feb;69(2):459–462. doi: 10.1073/pnas.69.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Daniel V., Litwack G., Tomkins G. M. Induction of cytolysis of cultured lymphoma cells by adenosine 3':5'-cyclic monophosphate and the isolation of resistant variants. Proc Natl Acad Sci U S A. 1973 Jan;70(1):76–79. doi: 10.1073/pnas.70.1.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Furmanski P., Silverman D. J., Lubin M. Expression of differentiated functions in mouse neuroblastoma mediated by dibutyryl-cyclic adenosine monophosphate. Nature. 1971 Oct 8;233(5319):413–415. doi: 10.1038/233413a0. [DOI] [PubMed] [Google Scholar]
  8. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Haseltine W. A., Block R., Gilbert W., Weber K. MSI and MSII made on ribosome in idling step of protein synthesis. Nature. 1972 Aug 18;238(5364):381–384. doi: 10.1038/238381a0. [DOI] [PubMed] [Google Scholar]
  10. Hershko A., Mamont P., Shields R., Tomkins G. M. "Pleiotypic response". Nat New Biol. 1971 Aug;232(33):206–211. [PubMed] [Google Scholar]
  11. Hsie A. W., Jones C., Puck T. T. Further changes in differentiation state accompanying the conversion of Chinese hamster cells of fibroblastic form by dibutyryl adenosine cyclic 3':5'-monophosphate and hormones. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1648–1652. doi: 10.1073/pnas.68.7.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hsie A. W., Puck T. T. Morphological transformation of Chinese hamster cells by dibutyryl adenosine cyclic 3':5'-monophosphate and testosterone. Proc Natl Acad Sci U S A. 1971 Feb;68(2):358–361. doi: 10.1073/pnas.68.2.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnson G. S., Friedman R. M., Pastan I. Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3':5'-cyclic monphosphate and its derivatives. Proc Natl Acad Sci U S A. 1971 Feb;68(2):425–429. doi: 10.1073/pnas.68.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maganiello V., Vaughan M. Prostaglandin E 1 effects on adenosine 3':5'-cyclic monophosphate concentration and phosphodiesterase activity in fibroblasts (mouse L cells-tissue culture-enzyme kinetics-prostaglandin homologues). Proc Natl Acad Sci U S A. 1972 Jan;69(1):269–273. doi: 10.1073/pnas.69.1.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mamont P., Hershko A., Kram R., Schacter L., Lust J., Tomkins G. M. The pleiotypic response in mammalian cells: search for an intracellular mediator. Biochem Biophys Res Commun. 1972 Sep 26;48(6):1378–1384. doi: 10.1016/0006-291x(72)90865-0. [DOI] [PubMed] [Google Scholar]
  16. Martin G. S., Venuta S., Weber M., Rubin H. Temperature-dependent alterations in sugar transport in cells infected by a temperature-sensitive mutant of Rous sarcoma virus. Proc Natl Acad Sci U S A. 1971 Nov;68(11):2739–2741. doi: 10.1073/pnas.68.11.2739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Masui H., Garren L. D. Inhibition of replication in functional mouse adrenal tumor cells by adrenocorticotropic hormone mediated by adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3206–3210. doi: 10.1073/pnas.68.12.3206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Otten J., Johnson G. S., Pastan I. Cyclic AMP levels in fibroblasts: relationship to growth rate and contact inhibition of growth. Biochem Biophys Res Commun. 1971 Sep;44(5):1192–1198. doi: 10.1016/s0006-291x(71)80212-7. [DOI] [PubMed] [Google Scholar]
  19. PRYOR J., BERTHET J. The action of adenosine 3',5'-monophosphate on the incorporation of leucine into liver proteins. Biochim Biophys Acta. 1960 Oct 7;43:556–557. doi: 10.1016/0006-3002(60)90484-4. [DOI] [PubMed] [Google Scholar]
  20. Pastan I., Perlman R. L. Cyclic AMP in metabolism. Nat New Biol. 1971 Jan 6;229(1):5–7. doi: 10.1038/newbio229005a0. [DOI] [PubMed] [Google Scholar]
  21. Peery C. V., Johnson G. S., Pastan I. Adenyl cyclase in normal and transformed fibroblasts in tissue culture. Activation by prostaglandins. J Biol Chem. 1971 Sep 25;246(18):5785–5790. [PubMed] [Google Scholar]
  22. Prasad K. N., Hsie A. W. Morphologic differentiation of mouse neuroblastoma cells induced in vitro by dibutyryl adenosine 3':5'-cyclic monophosphate. Nat New Biol. 1971 Sep 29;233(39):141–142. doi: 10.1038/newbio233141a0. [DOI] [PubMed] [Google Scholar]
  23. Prasad K. N. Morphological differentiation induced by prostaglandin in mouse neuroblastoma cells in culture. Nat New Biol. 1972 Mar 15;236(63):49–52. doi: 10.1038/newbio236049a0. [DOI] [PubMed] [Google Scholar]
  24. Ryan W. L., Durick M. A. Adenosine 3',5'-monophosphate and N 6 -2'-O-dibutyryl-adenosine 3',5'-monophosphate transport in cells. Science. 1972 Sep 15;177(4053):1002–1003. doi: 10.1126/science.177.4053.1002. [DOI] [PubMed] [Google Scholar]
  25. Shapiro L., Agabian-Keshishian N., Hirsch A., Rosen O. M. Effect of dibutyryladenosine 3':5'-cyclic monophosphate on growth and differentiation in Caulobacter crescentus. Proc Natl Acad Sci U S A. 1972 May;69(5):1225–1229. doi: 10.1073/pnas.69.5.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sheppard J. R. Difference in the cyclic adenosine 3',5'-monophosphate levels in normal and transformed cells. Nat New Biol. 1972 Mar 1;236(61):14–16. doi: 10.1038/newbio236014a0. [DOI] [PubMed] [Google Scholar]
  27. Sheppard J. R. Restoration of contact-inhibited growth to transformed cells by dibutyryl adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1316–1320. doi: 10.1073/pnas.68.6.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smulson M. E., Thomas J. Ribonucleic acid biosynthesis of human cells during amino acid deprivation. J Biol Chem. 1969 Oct 10;244(19):5309–5312. [PubMed] [Google Scholar]
  29. Yokota T., Gots J. S. Requirement of adenosine 3', 5'-cyclic phosphate for flagella formation in Escherichia coli and Salmonella typhimurium. J Bacteriol. 1970 Aug;103(2):513–516. doi: 10.1128/jb.103.2.513-516.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES