Skip to main content
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
. 1985 May;82(10):3277–3280. doi: 10.1073/pnas.82.10.3277

Pertussis toxin inhibits chemotactic peptide-stimulated generation of inositol phosphates and lysosomal enzyme secretion in human leukemic (HL-60) cells.

S J Brandt, R W Dougherty, E G Lapetina, J E Niedel
PMCID: PMC397758  PMID: 2860668

Abstract

The binding of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine to its cell surface receptor rapidly elicits the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C to form the putative second messengers inositol 1,4,5-trisphosphate and sn-1,2-diacylglycerol. To investigate the possible role of a guanine nucleotide binding protein in transduction of this membrane signal, we examined the effects of pertussis toxin on chemotactic peptide-stimulated inositol phospholipid metabolism in differentiated HL-60 cells labeled with [3H]inositol. Pertussis toxin inhibited the chemotactic tripeptide-stimulated production of inositol mono-, bis-, and trisphosphates and secretion of N-acetyl-beta-D-glucosaminidase in a time- and concentration-dependent manner. Treatment with pertussis toxin did not alter the total incorporation or the distribution of [3H]inositol in inositol phospholipid. Chemotactic peptide receptor number was unchanged, although a slight decrease in binding affinity was observed. These findings suggest a role for a guanine nucleotide binding protein in coupling the chemotactic peptide receptor to phospholipase C.

Full text

PDF
3277

Selected References

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

  1. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J. Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem J. 1983 Jun 15;212(3):849–858. doi: 10.1042/bj2120849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Billah M. M., Lapetina E. G. Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets. J Biol Chem. 1982 Nov 10;257(21):12705–12708. [PubMed] [Google Scholar]
  4. Bokoch G. M., Gilman A. G. Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin. Cell. 1984 Dec;39(2 Pt 1):301–308. doi: 10.1016/0092-8674(84)90008-4. [DOI] [PubMed] [Google Scholar]
  5. Bokoch G. M., Katada T., Northup J. K., Hewlett E. L., Gilman A. G. Identification of the predominant substrate for ADP-ribosylation by islet activating protein. J Biol Chem. 1983 Feb 25;258(4):2072–2075. [PubMed] [Google Scholar]
  6. Chaplinski T. J., Niedel J. E. Cyclic nucleotide-induced maturation of human promyelocytic leukemia cells. J Clin Invest. 1982 Nov;70(5):953–964. doi: 10.1172/JCI110707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cockcroft S., Bennett J. P., Gomperts B. D. Stimulus-secretion coupling in rabbit neutrophils is not mediated by phosphatidylinositol breakdown. Nature. 1980 Nov 20;288(5788):275–277. doi: 10.1038/288275a0. [DOI] [PubMed] [Google Scholar]
  8. Dougherty R. W., Godfrey P. P., Hoyle P. C., Putney J. W., Jr, Freer R. J. Secretagogue-induced phosphoinositide metabolism in human leucocytes. Biochem J. 1984 Sep 1;222(2):307–314. doi: 10.1042/bj2220307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Elks M. L., Watkins P. A., Manganiello V. C., Moss J., Hewlett E., Vaughan M. Selective regulation by pertussis toxin of insulin-induced activation of particulate cAMP phosphodiesterase activity in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 1983 Oct 31;116(2):593–598. doi: 10.1016/0006-291x(83)90565-x. [DOI] [PubMed] [Google Scholar]
  10. Gilman A. G. G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577–579. doi: 10.1016/0092-8674(84)90336-2. [DOI] [PubMed] [Google Scholar]
  11. Gomperts B. D. Involvement of guanine nucleotide-binding protein in the gating of Ca2+ by receptors. Nature. 1983 Nov 3;306(5938):64–66. doi: 10.1038/306064a0. [DOI] [PubMed] [Google Scholar]
  12. Hallcher L. M., Sherman W. R. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem. 1980 Nov 25;255(22):10896–10901. [PubMed] [Google Scholar]
  13. Hsia J. A., Moss J., Hewlett E. L., Vaughan M. ADP-ribosylation of adenylate cyclase by pertussis toxin. Effects on inhibitory agonist binding. J Biol Chem. 1984 Jan 25;259(2):1086–1090. [PubMed] [Google Scholar]
  14. Hyslop P. A., Oades Z. G., Jesaitis A. J., Painter R. G., Cochrane C. G., Sklar L. A. Evidence for N-formyl chemotactic peptide-stimulated GTPase activity in human neutrophil homogenates. FEBS Lett. 1984 Jan 23;166(1):165–169. doi: 10.1016/0014-5793(84)80065-4. [DOI] [PubMed] [Google Scholar]
  15. Irvine R. F., Letcher A. J., Lander D. J., Downes C. P. Inositol trisphosphates in carbachol-stimulated rat parotid glands. Biochem J. 1984 Oct 1;223(1):237–243. doi: 10.1042/bj2230237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koo C., Lefkowitz R. J., Snyderman R. Guanine nucleotides modulate the binding affinity of the oligopeptide chemoattractant receptor on human polymorphonuclear leukocytes. J Clin Invest. 1983 Sep;72(3):748–753. doi: 10.1172/JCI111045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kurose H., Katada T., Amano T., Ui M. Specific uncoupling by islet-activating protein, pertussis toxin, of negative signal transduction via alpha-adrenergic, cholinergic, and opiate receptors in neuroblastoma x glioma hybrid cells. J Biol Chem. 1983 Apr 25;258(8):4870–4875. [PubMed] [Google Scholar]
  18. Lad P. M., Glovsky M. M., Richards J. H., Learn D. B., Reisinger D. M., Smiley P. A. Identification of receptor regulatory proteins, membrane glycoproteins, and functional characteristics of adenylate cyclase in vesicles derived from the human neutrophil. Mol Immunol. 1984 Jul;21(7):627–639. doi: 10.1016/0161-5890(84)90048-8. [DOI] [PubMed] [Google Scholar]
  19. Lapetina E. G., Watson S. P., Cuatrecasas P. myo-Inositol 1,4,5-trisphosphate stimulates protein phosphorylation in saponin-permeabilized human platelets. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7431–7435. doi: 10.1073/pnas.81.23.7431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Molski T. F., Naccache P. H., Marsh M. L., Kermode J., Becker E. L., Sha'afi R. I. Pertussis toxin inhibits the rise in the intracellular concentration of free calcium that is induced by chemotactic factors in rabbit neutrophils: possible role of the "G proteins" in calcium mobilization. Biochem Biophys Res Commun. 1984 Oct 30;124(2):644–650. doi: 10.1016/0006-291x(84)91603-6. [DOI] [PubMed] [Google Scholar]
  21. Nakamura T., Ui M. Islet-activating protein, pertussis toxin, inhibits Ca2+-induced and guanine nucleotide-dependent releases of histamine and arachidonic acid from rat mast cells. FEBS Lett. 1984 Aug 6;173(2):414–418. doi: 10.1016/0014-5793(84)80816-9. [DOI] [PubMed] [Google Scholar]
  22. Neer E. J., Lok J. M., Wolf L. G. Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase. J Biol Chem. 1984 Nov 25;259(22):14222–14229. [PubMed] [Google Scholar]
  23. Niedel J. E., Cuatrecasas P. Formyl peptide chemotactic receptors of leukocytes and macrophages. Curr Top Cell Regul. 1980;17:137–170. doi: 10.1016/b978-0-12-152817-1.50009-2. [DOI] [PubMed] [Google Scholar]
  24. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  25. Okajima F., Ui M. ADP-ribosylation of the specific membrane protein by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils. A possible role of the toxin substrate in Ca2+-mobilizing biosignaling. J Biol Chem. 1984 Nov 25;259(22):13863–13871. [PubMed] [Google Scholar]
  26. Serhan C. N., Broekman M. J., Korchak H. M., Marcus A. J., Weissmann G. Endogenous phospholipid metabolism in stimulated neutrophils differential activation by FMLP and PMA. Biochem Biophys Res Commun. 1982 Aug;107(3):951–958. doi: 10.1016/0006-291x(82)90615-5. [DOI] [PubMed] [Google Scholar]
  27. Shefcyk J., Yassin R., Volpi M., Molski T. F., Naccache P. H., Munoz J. J., Becker E. L., Feinstein M. B., Sha'afi R. I. Pertussis but not cholera toxin inhibits the stimulated increase in actin association with the cytoskeleton in rabbit neutrophils: role of the "G proteins" in stimulus-response coupling. Biochem Biophys Res Commun. 1985 Feb 15;126(3):1174–1181. doi: 10.1016/0006-291x(85)90309-2. [DOI] [PubMed] [Google Scholar]
  28. Snyderman R., Pike M. C. Chemoattractant receptors on phagocytic cells. Annu Rev Immunol. 1984;2:257–281. doi: 10.1146/annurev.iy.02.040184.001353. [DOI] [PubMed] [Google Scholar]
  29. Snyderman R., Pike M. C., Edge S., Lane B. A chemoattractant receptor on macrophages exists in two affinity states regulated by guanine nucleotides. J Cell Biol. 1984 Feb;98(2):444–448. doi: 10.1083/jcb.98.2.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sternweis P. C., Robishaw J. D. Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J Biol Chem. 1984 Nov 25;259(22):13806–13813. [PubMed] [Google Scholar]
  31. Van Dop C., Yamanaka G., Steinberg F., Sekura R. D., Manclark C. R., Stryer L., Bourne H. R. ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors. J Biol Chem. 1984 Jan 10;259(1):23–26. [PubMed] [Google Scholar]
  32. Verghese M. W., Smith C. D., Snyderman R. Potential role for a guanine nucleotide regulatory protein in chemoattractant receptor mediated polyphosphoinositide metabolism, Ca++ mobilization and cellular responses by leukocytes. Biochem Biophys Res Commun. 1985 Mar 15;127(2):450–457. doi: 10.1016/s0006-291x(85)80181-9. [DOI] [PubMed] [Google Scholar]
  33. Volpi M., Yassin R., Naccache P. H., Sha'afi R. I. Chemotactic factor causes rapid decreases in phosphatidylinositol,4,5-bisphosphate and phosphatidylinositol 4-monophosphate in rabbit neutrophils. Biochem Biophys Res Commun. 1983 May 16;112(3):957–964. doi: 10.1016/0006-291x(83)91711-4. [DOI] [PubMed] [Google Scholar]
  34. Watson S. P., McConnell R. T., Lapetina E. G. The rapid formation of inositol phosphates in human platelets by thrombin is inhibited by prostacyclin. J Biol Chem. 1984 Nov 10;259(21):13199–13203. [PubMed] [Google Scholar]
  35. Whitman M. R., Epstein J., Cantley L. Inositol 1,4,5-trisphosphate stimulates phosphorylation of a 62,000-dalton protein in monkey fibroblast and bovine brain cell lysates. J Biol Chem. 1984 Nov 25;259(22):13652–13655. [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