Skip to main content
PMC 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
. 1976 Dec;73(12):4555–4559. doi: 10.1073/pnas.73.12.4555

An 18,000 molecular weight polypeptide induces early events and stimulates DNA synthesis in cultured cells.

H R Bourne, E Rozengurt
PMCID: PMC431539  PMID: 188046

Abstract

Extracts of serum-free medium, conditioned by contact with SV40-transformed BHK cells, stimulate DNA synthesis in cultured fibroblasts. From this source, we have purified a homogenous basic protein of 18,000 molecular weight, termed fibroblast derived growth factor. In submicrogram quantities, fibroblast derived growth factor stimulates DNA synthesis in mouse 3T3 cells, in the absence of added serum. Prior to the onset of DNA synthesis, both serum and fibroblast derived growth factor induce an array of nearly simultaneous biochemical changes in the membrane to 3T3 cells that include stimulation of the uptake of nucleosides, 2-deoxyglucose, and 86Rb+. These results strongly suggest that the early events are integral components of the proliferative response, rather than coincidental effects of nonmitogenic molecules present in serum.

Full text

PDF
4557

Images in this article

4556Image
on p.4556

Selected References

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

  1. Antoniades H. N., Stathakos D., Scher C. D. Isolation of a cationic polypeptide from human serum that stimulates proliferation of 3T3 cells. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2635–2639. doi: 10.1073/pnas.72.7.2635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Armelin H. A. Pituitary extracts and steroid hormones in the control of 3T3 cell growth. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2702–2706. doi: 10.1073/pnas.70.9.2702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bradley W. E., Culp L. A. Stimulation of 2-deoxyglucose uptake in growth-inhibited BALB-C 3T3 and revertant SV40-transformed 3T3 cells. Exp Cell Res. 1974 Mar 15;84(1):335–350. doi: 10.1016/0014-4827(74)90413-3. [DOI] [PubMed] [Google Scholar]
  4. Bürk R. R. A factor from a transformed cell line that affects cell migration. Proc Natl Acad Sci U S A. 1973 Feb;70(2):369–372. doi: 10.1073/pnas.70.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen S. PURIFICATION OF A NERVE-GROWTH PROMOTING PROTEIN FROM THE MOUSE SALIVARY GLAND AND ITS NEURO-CYTOTOXIC ANTISERUM. Proc Natl Acad Sci U S A. 1960 Mar;46(3):302–311. doi: 10.1073/pnas.46.3.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cunningham D. D., Pardee A. B. Transport changes rapidly initiated by serum addition to "contact inhibited" 3T3 cells. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1049–1056. doi: 10.1073/pnas.64.3.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dulak N. C., Temin H. M. A partially purified polypeptide fraction from rat liver cell conditioned medium with multiplication-stimulating activity for embryo fibroblasts. J Cell Physiol. 1973 Apr;81(2):153–160. doi: 10.1002/jcp.1040810204. [DOI] [PubMed] [Google Scholar]
  8. Dulbecco R., Elkington J. Conditions limiting multiplication of fibroblastic and epithelial cells in dense cultures. Nature. 1973 Nov 23;246(5430):197–199. doi: 10.1038/246197a0. [DOI] [PubMed] [Google Scholar]
  9. Fryklund L., Uthne K., Sievertsson H. Isolation and characterization of polypeptides from human plasma enhancing the growth of human normal cells in culture. Biochem Biophys Res Commun. 1974 Dec 11;61(3):950–956. doi: 10.1016/0006-291x(74)90247-2. [DOI] [PubMed] [Google Scholar]
  10. Gospodarowicz D. Purification of a fibroblast growth factor from bovine pituitary. J Biol Chem. 1975 Apr 10;250(7):2515–2520. [PubMed] [Google Scholar]
  11. Hershko A., Mamont P., Shields R., Tomkins G. M. "Pleiotypic response". Nat New Biol. 1971 Aug;232(33):206–211. [PubMed] [Google Scholar]
  12. Holley R. W., Kiernan J. A. "Contact inhibition" of cell division in 3T3 cells. Proc Natl Acad Sci U S A. 1968 May;60(1):300–304. doi: 10.1073/pnas.60.1.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jimenez de Asua L., Rozengurt E. Multiple control mechanisms underlie initiation of growth in animal cells. Nature. 1974 Oct 18;251(5476):624–626. doi: 10.1038/251624a0. [DOI] [PubMed] [Google Scholar]
  14. Lipton A., Klinger I., Paul D., Holley R. W. Migration of mouse 3T3 fibroblasts in response to a serum factor. Proc Natl Acad Sci U S A. 1971 Nov;68(11):2799–2801. doi: 10.1073/pnas.68.11.2799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lipton A., Paul D., Henahan M., Klinger I., Holley R. W. Serum requirements for survival of 3T3 and SV3T3 fibroblasts. Exp Cell Res. 1972 Oct;74(2):466–470. doi: 10.1016/0014-4827(72)90402-8. [DOI] [PubMed] [Google Scholar]
  16. Murphy R. A., Pantazis N. J., Arnason B. G., Young M. Secretion of a nerve growth factor by mouse neuroblastoma cells in culture. Proc Natl Acad Sci U S A. 1975 May;72(5):1895–1898. doi: 10.1073/pnas.72.5.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pastan I. H., Johnson G. S., Anderson W. B. Role of cyclic nucleotides in growth control. Annu Rev Biochem. 1975;44:491–522. doi: 10.1146/annurev.bi.44.070175.002423. [DOI] [PubMed] [Google Scholar]
  18. Rozengurt E., Heppel L. A. Serum rapidly stimulates ouabain-sensitive 86-RB+ influx in quiescent 3T3 cells. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4492–4495. doi: 10.1073/pnas.72.11.4492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rozengurt E., Jimenez de Asua L. Role of cyclic 3':5'-adenosine monophosphate in the early transport changes induced by serum and insulin in quiescent fibroblasts. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3609–3612. doi: 10.1073/pnas.70.12.3609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shodell M. Environmental stimuli in the progression of BHK-21 cells through the cell cycle. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1455–1459. doi: 10.1073/pnas.69.6.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith J. A., Martin L. Do cells cycle? Proc Natl Acad Sci U S A. 1973 Apr;70(4):1263–1267. doi: 10.1073/pnas.70.4.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Spieker-Polet H., Polet H. Identification of albumin as the serum factor essential for the growth of activated human lymphocytes. J Biol Chem. 1976 Feb 25;251(4):987–992. [PubMed] [Google Scholar]
  23. Stoker M. G., Clarke G. D., Thornton M. Density dependent stimulation of thymidine incorporation in BHK21 cells by active material released from the same cells. J Cell Physiol. 1971 Dec;78(3):345–354. doi: 10.1002/jcp.1040780304. [DOI] [PubMed] [Google Scholar]
  24. TODARO G. J., GREEN H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963 May;17:299–313. doi: 10.1083/jcb.17.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Temin H. M. Stimulation by serum of multiplication of stationary chicken cells. J Cell Physiol. 1971 Oct;78(2):161–170. doi: 10.1002/jcp.1040780202. [DOI] [PubMed] [Google Scholar]
  26. WAYMOUTH C. Rapid proliferation of sublines of NCTC clone 929 (strain L) mouse cells in a simple chemically defined medium (MB 752/1). J Natl Cancer Inst. 1959 May;22(5):1003–1017. doi: 10.1093/jnci/22.5.1003. [DOI] [PubMed] [Google Scholar]
  27. Wolf L., Kohler N., Roehm C., Lipton A. Initiation of DNA synthesis in mouse 3T3 fibroblasts in response to a specific factor. Exp Cell Res. 1975 Apr;92(1):63–69. doi: 10.1016/0014-4827(75)90637-0. [DOI] [PubMed] [Google Scholar]
  28. de Asua L. J., Rozengurt E., Dulbecco R. Kinetics of early changes in phosphate and uridine transport and cyclic AMP levels stimulated by serum in density-inhibited 3T3 cells. Proc Natl Acad Sci U S A. 1974 Jan;71(1):96–98. doi: 10.1073/pnas.71.1.96. [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