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
. 1987 Jan;84(2):324–328. doi: 10.1073/pnas.84.2.324

Polylysine-containing peptides, including the carboxyl-terminal segment of the human c-Ki-ras 2 protein, affect the activity of some key membrane enzymes.

M Gatica, C C Allende, M Antonelli, J E Allende
PMCID: PMC304199  PMID: 3025867

Abstract

Polylysine-containing peptides are found to affect membrane protein kinases, phosphatidylinositol kinases, and adenylate cyclase. Poly(L-lysine), poly(D-lysine), random copolymers of lysine and serine or lysine and alanine, and poly(L-ornithine) produced large increases in the in vitro phosphorylation of some membrane proteins present in Xenopus laevis oocyte membranes. Poly(L-arginine) did not cause a similar stimulation. In these membranes the phosphorylation of polydisperse protein of approximately 25 kDa was also greatly increased by 1 mM spermine and spermidine, by 10 microM histone H1, or by 200 microM peptide containing the 14-residue sequence at the carboxyl terminus of the human c-Ki-ras 2 gene product, which has eight lysines. Similar specific stimulation of protein phosphorylation was observed with membranes of NG-108-15 nerve cells in culture. Polylysine peptides, including the c-Ki-ras 2 segment, also stimulate the in vitro phosphorylation of membrane inositolphospholipids, to produce mainly phosphatidylinositol 4-phosphate and less phosphatidylinositol 4,5-bisphosphate. Polylysine also alters the activity of oocyte adenylate cyclase, assayed in the presence of either F- or 5'-guanylyl imidodiphosphate.

Full text

PDF
328

Images in this article

325Image
on p.325
325Image
on p.325
325Image
on p.325
326Image
on p.326
326Image
on p.326
326Image
on p.326
326Image
on p.326
326Image
on p.326

Selected References

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

  1. Abdel-Ghany M., Riegler C., Racker E. A placental polypeptide activator of a membranous protein kinase and its relation to histone 1. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7388–7391. doi: 10.1073/pnas.81.23.7388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Birchmeier C., Broek D., Wigler M. ras proteins can induce meiosis in Xenopus oocytes. Cell. 1985 Dec;43(3 Pt 2):615–621. doi: 10.1016/0092-8674(85)90233-8. [DOI] [PubMed] [Google Scholar]
  3. Birnbaumer L., Codina J., Mattera R., Cerione R. A., Hildebrandt J. D., Sunyer T., Rojas F. J., Caron M. G., Lefkowitz R. J., Iyengar R. Regulation of hormone receptors and adenylyl cyclases by guanine nucleotide binding N proteins. Recent Prog Horm Res. 1985;41:41–99. doi: 10.1016/b978-0-12-571141-8.50006-8. [DOI] [PubMed] [Google Scholar]
  4. Broek D., Samiy N., Fasano O., Fujiyama A., Tamanoi F., Northup J., Wigler M. Differential activation of yeast adenylate cyclase by wild-type and mutant RAS proteins. Cell. 1985 Jul;41(3):763–769. doi: 10.1016/s0092-8674(85)80057-x. [DOI] [PubMed] [Google Scholar]
  5. Capon D. J., Seeburg P. H., McGrath J. P., Hayflick J. S., Edman U., Levinson A. D., Goeddel D. V. Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations. Nature. 1983 Aug 11;304(5926):507–513. doi: 10.1038/304507a0. [DOI] [PubMed] [Google Scholar]
  6. Cook G. H., Wolff J. Melittin interactions with adenylate cyclase. Biochim Biophys Acta. 1977 Jun 23;498(1):255–258. doi: 10.1016/0304-4165(77)90106-4. [DOI] [PubMed] [Google Scholar]
  7. Fasano O., Taparowsky E., Fiddes J., Wigler M., Goldfarb M. Sequence and structure of the coding region of the human H-ras-1 gene from T24 bladder carcinoma cells. J Mol Appl Genet. 1983;2(2):173–180. [PubMed] [Google Scholar]
  8. Fleischman L. F., Chahwala S. B., Cantley L. ras-transformed cells: altered levels of phosphatidylinositol-4,5-bisphosphate and catabolites. Science. 1986 Jan 24;231(4736):407–410. doi: 10.1126/science.3001936. [DOI] [PubMed] [Google Scholar]
  9. Ham R. G., McKeehan W. L. Media and growth requirements. Methods Enzymol. 1979;58:44–93. doi: 10.1016/s0076-6879(79)58126-9. [DOI] [PubMed] [Google Scholar]
  10. Harwood J. L., Hawthorne J. N. Metabolism of the phosphoinositides in guinea-pig brain synaptosomes. J Neurochem. 1969 Sep;16(9):1377–1387. doi: 10.1111/j.1471-4159.1969.tb05989.x. [DOI] [PubMed] [Google Scholar]
  11. Hathaway G. M., Lubben T. H., Traugh J. A. Inhibition of casein kinase II by heparin. J Biol Chem. 1980 Sep 10;255(17):8038–8041. [PubMed] [Google Scholar]
  12. Jordana X., Olate J., Allende C. C., Allende J. E. Studies on the mechanism of inhibition of amphibian oocyte adenylate cyclase by progesterone. Arch Biochem Biophys. 1984 Feb 1;228(2):379–387. doi: 10.1016/0003-9861(84)90001-8. [DOI] [PubMed] [Google Scholar]
  13. KATCHALSKY A., DANON D., NEVO A. Interactions of basic polyelectrolytes with the red blood cell. II. Agglutination of red blood cells by polymeric bases. Biochim Biophys Acta. 1959 May;33(1):120–138. doi: 10.1016/0006-3002(59)90505-0. [DOI] [PubMed] [Google Scholar]
  14. Koski G., Klee W. A. Opiates inhibit adenylate cyclase by stimulating GTP hydrolysis. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4185–4189. doi: 10.1073/pnas.78.7.4185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Madaule P., Axel R. A novel ras-related gene family. Cell. 1985 May;41(1):31–40. doi: 10.1016/0092-8674(85)90058-3. [DOI] [PubMed] [Google Scholar]
  17. McGrath J. P., Capon D. J., Smith D. H., Chen E. Y., Seeburg P. H., Goeddel D. V., Levinson A. D. Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene. Nature. 1983 Aug 11;304(5926):501–506. doi: 10.1038/304501a0. [DOI] [PubMed] [Google Scholar]
  18. NEVO A., DE VRIES A., KATCHALSKY A. Interaction of basic polyamino acids with the red blood cell. I. Combination of polylysine with single cells. Biochim Biophys Acta. 1955 Aug;17(4):536–547. doi: 10.1016/0006-3002(55)90416-9. [DOI] [PubMed] [Google Scholar]
  19. Neuman-Silberberg F. S., Schejter E., Hoffmann F. M., Shilo B. Z. The Drosophila ras oncogenes: structure and nucleotide sequence. Cell. 1984 Jul;37(3):1027–1033. doi: 10.1016/0092-8674(84)90437-9. [DOI] [PubMed] [Google Scholar]
  20. Powers S., Kataoka T., Fasano O., Goldfarb M., Strathern J., Broach J., Wigler M. Genes in S. cerevisiae encoding proteins with domains homologous to the mammalian ras proteins. Cell. 1984 Mar;36(3):607–612. doi: 10.1016/0092-8674(84)90340-4. [DOI] [PubMed] [Google Scholar]
  21. Quinton P. M., Philpott C. W. A role for anionic sites in epithelial architecture. Effects of cationic polymers on cell membrane structure. J Cell Biol. 1973 Mar;56(3):787–796. doi: 10.1083/jcb.56.3.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Racker E., Abdel-Ghany M., Sherrill K., Riegler C., Blair E. A. New protein kinase from plasma membrane of Ehrlich ascites tumor cells activated by natural polypeptides. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4250–4254. doi: 10.1073/pnas.81.14.4250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reymond C. D., Gomer R. H., Mehdy M. C., Firtel R. A. Developmental regulation of a Dictyostelium gene encoding a protein homologous to mammalian ras protein. Cell. 1984 Nov;39(1):141–148. doi: 10.1016/0092-8674(84)90199-5. [DOI] [PubMed] [Google Scholar]
  24. Schindler M., Koppel D. E., Sheetz M. P. Modulation of membrane protein lateral mobility by polyphosphates and polyamines. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1457–1461. doi: 10.1073/pnas.77.3.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schook W. J., Puszkin S. Brain clathrin light chain 2 can be phosphorylated by a coated vesicle kinase. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8039–8043. doi: 10.1073/pnas.82.23.8039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sefton B. M., Trowbridge I. S., Cooper J. A., Scolnick E. M. The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid. Cell. 1982 Dec;31(2 Pt 1):465–474. doi: 10.1016/0092-8674(82)90139-8. [DOI] [PubMed] [Google Scholar]
  27. Shimizu K., Birnbaum D., Ruley M. A., Fasano O., Suard Y., Edlund L., Taparowsky E., Goldfarb M., Wigler M. Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1. Nature. 1983 Aug 11;304(5926):497–500. doi: 10.1038/304497a0. [DOI] [PubMed] [Google Scholar]
  28. Tabor C. W., Tabor H. 1,4-Diaminobutane (putrescine), spermidine, and spermine. Annu Rev Biochem. 1976;45:285–306. doi: 10.1146/annurev.bi.45.070176.001441. [DOI] [PubMed] [Google Scholar]
  29. Taparowsky E., Shimizu K., Goldfarb M., Wigler M. Structure and activation of the human N-ras gene. Cell. 1983 Sep;34(2):581–586. doi: 10.1016/0092-8674(83)90390-2. [DOI] [PubMed] [Google Scholar]
  30. Vogel S., Hoppe J. Polyamines stimulate the phosphorylation of phosphatidylinositol in membranes from A431 cells. Eur J Biochem. 1986 Jan 15;154(2):253–257. doi: 10.1111/j.1432-1033.1986.tb09390.x. [DOI] [PubMed] [Google Scholar]
  31. Weeks M. O., Hager G. L., Lowe R., Scolnick E. M. Development and analysis of a transformation-defective mutant of Harvey murine sarcoma tk virus and its gene product. J Virol. 1985 May;54(2):586–597. doi: 10.1128/jvi.54.2.586-597.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Weinberg R. A. The action of oncogenes in the cytoplasm and nucleus. Science. 1985 Nov 15;230(4727):770–776. doi: 10.1126/science.2997917. [DOI] [PubMed] [Google Scholar]
  33. Wolff J., Cook G. H. Charge effects in the activation of adenylate cyclase. J Biol Chem. 1975 Sep 10;250(17):6897–6903. [PubMed] [Google Scholar]
  34. Yano K., Higashida H., Inoue R., Nozawa Y. Bradykinin-induced rapid breakdown of phosphatidylinositol 4,5-bisphosphate in neuroblastoma X glioma hybrid NG108-15 cells. J Biol Chem. 1984 Aug 25;259(16):10201–10207. [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