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
. 1975 Feb;72(2):413–417. doi: 10.1073/pnas.72.2.413

The role of surface proteins in cell proliferation as studied with thrombin and other proteases.

N N Teng, L Bo Chen
PMCID: PMC432321  PMID: 1054823

Abstract

This communication explores the capacity of different proteases to stimulate DNA synthesis in resting chick embryo fibroblasts and to cause the removal of cell membrane proteins previosly postulated as important in the regulation of growth and division of cells. Thrombin, a highly specific protease and a known mitogen, was incubated with chick embryo fibroblasts, and analysis was made of the cell membrane proteins. Of particular interest were a protein of molecular weight 250,000, which is known to be readily removed by the action of trypsin and is not present in most transformed cells, and two other proteins, which are reduced in amount in transformed as compared to confluent resting cell cultures. None of these three proteins was removed by thrombin when the latter was added to confluent cells in concentrations sufficient to cause significant increase in DNA synthesis twelve hours after stimulation by the protease. The presence or absence of these proteins in the membranes of confluent resting or transformed cells of chick embryo fibroblasts does not seem to be directly related to the process of regulation of DNA synthesis and cellular division.

Full text

PDF
413

Images in this article

415Image
on p.415

Selected References

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

  1. Baenziger N. L., Brodie G. N., Majerus P. W. A thrombin-sensitive protein of human platelet membranes. Proc Natl Acad Sci U S A. 1971 Jan;68(1):240–243. doi: 10.1073/pnas.68.1.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baenziger N. L., Brodie G. N., Majerus P. W. Isolation and properties of a thrombin-sensitive protein of human platelets. J Biol Chem. 1972 May 10;247(9):2723–2731. [PubMed] [Google Scholar]
  3. Burger M. M. Proteolytic enzymes initiating cell division and escape from contact inhibition of growth. Nature. 1970 Jul 11;227(5254):170–171. doi: 10.1038/227170a0. [DOI] [PubMed] [Google Scholar]
  4. Chen L. B., Buchanan J. M. Mitogenic activity of blood components. I. Thrombin and prothrombin. Proc Natl Acad Sci U S A. 1975 Jan;72(1):131–135. doi: 10.1073/pnas.72.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Engel A., Alexander B., Pechet L. Activation of trypsinogen and plasminogen by thrombin preparations. Biochemistry. 1966 May;5(5):1543–1551. doi: 10.1021/bi00869a014. [DOI] [PubMed] [Google Scholar]
  6. Gahmberg C. G., Hakomori S. Organization of glycolipids and glycoproteins in surface membranes: dependency on cell cycle and on transformation. Biochem Biophys Res Commun. 1974 Jul 10;59(1):283–291. doi: 10.1016/s0006-291x(74)80204-4. [DOI] [PubMed] [Google Scholar]
  7. Hogg N. M. A comparison of membrane proteins of normal and transformed cells by lactoperoxidase labeling. Proc Natl Acad Sci U S A. 1974 Feb;71(2):489–492. doi: 10.1073/pnas.71.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hynes R. O. Alteration of cell-surface proteins by viral transformation and by proteolysis. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3170–3174. doi: 10.1073/pnas.70.11.3170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hynes R. O., Humphryes K. C. Characterization of the external proteins of hamster fibroblasts. J Cell Biol. 1974 Aug;62(2):438–448. doi: 10.1083/jcb.62.2.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Muszbek L., Laki K. Cleavage of actin by thrombin. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2208–2211. doi: 10.1073/pnas.71.6.2208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nachman R. L., Hubbard A., Ferris B. Iodination of the human platelet membrane. Studies of the major surface glycoprotein. J Biol Chem. 1973 Apr 25;248(8):2928–2936. [PubMed] [Google Scholar]
  13. Ossowski L., Quigley J. P., Kellerman G. M., Reich E. Fibrinolysis associated with oncogenic transformation. Requirement of plasminogen for correlated changes in cellular morphology, colony formation in agar, and cell migration. J Exp Med. 1973 Nov 1;138(5):1056–1064. doi: 10.1084/jem.138.5.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Phillips D. R., Agin P. P. Thrombin substrates and the proteolytic site of thrombin action on human-platelet plasma membranes. Biochim Biophys Acta. 1974 Jun 13;352(2):218–227. doi: 10.1016/0005-2736(74)90213-2. [DOI] [PubMed] [Google Scholar]
  15. Phillips D. R. Effect of trypsin on the exposed polypeptides and glycoproteins in the human platelet membrane. Biochemistry. 1972 Nov 21;11(24):4582–4588. doi: 10.1021/bi00774a025. [DOI] [PubMed] [Google Scholar]
  16. Phillips D. R., Morrison M. Exposed protein on the intact human erythrocyte. Biochemistry. 1971 May 11;10(10):1766–1771. doi: 10.1021/bi00786a006. [DOI] [PubMed] [Google Scholar]
  17. Poduslo J. F., Greenberg C. S., Glick M. C. Proteins exposed on the surface of mammalian membranes. Biochemistry. 1972 Jul 4;11(14):2616–2621. doi: 10.1021/bi00764a011. [DOI] [PubMed] [Google Scholar]
  18. Rein A., Rubin H. Effects of local cell concentrations upon the growth of chick embryo cells in tissue culture. Exp Cell Res. 1968 Mar;49(3):666–678. doi: 10.1016/0014-4827(68)90213-9. [DOI] [PubMed] [Google Scholar]
  19. Ruoslahti E., Vaheri A., Kuusela P., Linder E. Fibroblast surface antigen: a new serum protein. Biochim Biophys Acta. 1973 Oct 18;322(2):352–358. doi: 10.1016/0005-2795(73)90310-3. [DOI] [PubMed] [Google Scholar]
  20. Ruoslahti E., Vaheri A. Novel human serum protein from fibroblast plasma membrane. Nature. 1974 Apr 26;248(5451):789–791. doi: 10.1038/248789a0. [DOI] [PubMed] [Google Scholar]
  21. Schnebli H. P., Burger M. M. Selective inhibition of growth of transformed cells by protease inhibitors. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3825–3827. doi: 10.1073/pnas.69.12.3825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sefton B. M., Rubin H. Release from density dependent growth inhibition by proteolytic enzymes. Nature. 1970 Aug 22;227(5260):843–845. doi: 10.1038/227843a0. [DOI] [PubMed] [Google Scholar]
  23. Stone K. R., Smith R. E., Joklik W. K. Changes in membrane polypeptides that occur when chick embryo fibroblasts and NRK cells are transformed with avian sarcoma viruses. Virology. 1974 Mar;58(1):86–100. doi: 10.1016/0042-6822(74)90143-3. [DOI] [PubMed] [Google Scholar]
  24. Studier F. W. Bacteriophage T7. Science. 1972 Apr 28;176(4033):367–376. doi: 10.1126/science.176.4033.367. [DOI] [PubMed] [Google Scholar]
  25. Wickus G. G., Robbins P. W. Plasma membrane proteins of normal and Rous sarcoma virus-transformed chick-embryo fibroblasts. Nat New Biol. 1973 Sep 19;245(142):65–67. doi: 10.1038/newbio245065a0. [DOI] [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