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. 1989 Sep 15;262(3):829–834. doi: 10.1042/bj2620829

Regulation of GH3 pituitary tumour-cell adenylate cyclase activity by activators of protein kinase C.

L A Quilliam 1, P R Dobson 1, B L Brown 1
PMCID: PMC1133348  PMID: 2480108

Abstract

The influence of protein kinase C (PKC) activation on cyclic AMP production in GH3 cells has been studied. The stimulation of cyclic AMP accumulation induced by forskolin and cholera toxin was potentiated by 4 beta-phorbol 12,13-dibutyrate (PDBu). Moreover, PDBu, which causes attenuation of the maximal response to vasoactive intestinal polypeptide (VIP), also induced a small right shift in the dose-response curve for VIP-induced cyclic AMP accumulation. PDBu-stimulated cyclic AMP accumulation was unaffected by pretreatment of cells with pertussis toxin or the inhibitory muscarinic agonist, oxotremorine. PDBu stimulation of adenylate cyclase activity required the presence of a cytosolic factor which appeared to translocate to the plasma membrane in response to the phorbol ester. The diacylglycerol-generating agents thyroliberin, bombesin and bacterial phospholipase C each stimulated cyclic AMP accumulation, but, unlike PDBu, did not attenuate the stimulation induced by VIP. These results suggest that PKC affects at least two components of the adenylate cyclase complex. Stimulation of cyclic AMP accumulation is probably due to modification of the catalytic subunit, whereas attenuation of VIP-stimulated cyclic AMP accumulation appears to be due to the phosphorylation of a different site, which may be the VIP receptor.

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Selected References

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

  1. Barovsky K., Brooker G. Forskolin potentiation of cholera toxin-stimulated cyclic AMP accumulation in intact C6-2B cells. Evidence for enhanced Gs-C coupling. Mol Pharmacol. 1985 Dec;28(6):502–507. [PubMed] [Google Scholar]
  2. Bell J. D., Brunton L. L. Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters. Withdrawal of GTP-dependent inhibition. J Biol Chem. 1986 Sep 15;261(26):12036–12041. [PubMed] [Google Scholar]
  3. Bell J. D., Buxton I. L., Brunton L. L. Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters. Putative effect of C kinase on alpha s-GTP-catalytic subunit interaction. J Biol Chem. 1985 Mar 10;260(5):2625–2628. [PubMed] [Google Scholar]
  4. Bell R. M. Protein kinase C activation by diacylglycerol second messengers. Cell. 1986 Jun 6;45(5):631–632. doi: 10.1016/0092-8674(86)90774-9. [DOI] [PubMed] [Google Scholar]
  5. Blackshear P. J., Stumpo D. J., Huang J. K., Nemenoff R. A., Spach D. H. Protein kinase C-dependent and -independent pathways of proto-oncogene induction in human astrocytoma cells. J Biol Chem. 1987 Jun 5;262(16):7774–7781. [PubMed] [Google Scholar]
  6. Bozou J. C., Couvineau A., Rouyer-Fessard C., Laburthe M., Vincent J. P., Kitabgi P. Phorbol ester induces loss of VIP stimulation of adenylate cyclase and VIP-binding sites in HT29 cells. FEBS Lett. 1987 Jan 26;211(2):151–154. doi: 10.1016/0014-5793(87)81426-6. [DOI] [PubMed] [Google Scholar]
  7. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  8. Brown B. L., Wojcikiewicz R. J., Dobson P. R., Robinson A., Irons L. I. Pertussis toxin blocks the inhibitory effect of muscarinic cholinergic agonists on cyclic AMP accumulation and prolactin secretion in GH3 anterior-pituitary tumour cells. Biochem J. 1984 Oct 1;223(1):145–149. doi: 10.1042/bj2230145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coussens L., Parker P. J., Rhee L., Yang-Feng T. L., Chen E., Waterfield M. D., Francke U., Ullrich A. Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science. 1986 Aug 22;233(4766):859–866. doi: 10.1126/science.3755548. [DOI] [PubMed] [Google Scholar]
  10. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gill D. M. Mechanism of action of cholera toxin. Adv Cyclic Nucleotide Res. 1977;8:85–118. [PubMed] [Google Scholar]
  12. Gopalakrishna R., Barsky S. H., Thomas T. P., Anderson W. B. Factors influencing chelator-stable, detergent-extractable, phorbol diester-induced membrane association of protein kinase C. Differences between Ca2+-induced and phorbol ester-stabilized membrane bindings of protein kinase C. J Biol Chem. 1986 Dec 15;261(35):16438–16445. [PubMed] [Google Scholar]
  13. Guild S., Drummond A. H. Vasoactive-intestinal-polypeptide-stimulated adenosine 3',5'-cyclic monophosphate accumulation in GH3 pituitary tumour cells. Reversal of desensitization by forskolin. Biochem J. 1984 Aug 1;221(3):789–796. doi: 10.1042/bj2210789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jakobs K. H., Aktories K., Schultz G. Mechanism of pertussis toxin action on the adenylate cyclase system. Inhibition of the turn-on reaction of the inhibitory regulatory site. Eur J Biochem. 1984 Apr 2;140(1):177–181. doi: 10.1111/j.1432-1033.1984.tb08083.x. [DOI] [PubMed] [Google Scholar]
  15. Jakobs K. H., Bauer S., Watanabe Y. Modulation of adenylate cyclase of human platelets by phorbol ester. Impairment of the hormone-sensitive inhibitory pathway. Eur J Biochem. 1985 Sep 2;151(2):425–430. doi: 10.1111/j.1432-1033.1985.tb09119.x. [DOI] [PubMed] [Google Scholar]
  16. Johnson J. A., Goka T. J., Clark R. B. Phorbol ester-induced augmentation and inhibition of epinephrine-stimulated adenylate cyclase in S49 lymphoma cells. J Cyclic Nucleotide Protein Phosphor Res. 1986;11(3):199–215. [PubMed] [Google Scholar]
  17. Katada T., Gilman A. G., Watanabe Y., Bauer S., Jakobs K. H. Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem. 1985 Sep 2;151(2):431–437. doi: 10.1111/j.1432-1033.1985.tb09120.x. [DOI] [PubMed] [Google Scholar]
  18. Kiss Z., Luo Y. A. Phorbol ester and 1,2-diolein are not fully equivalent activators of protein kinase C in respect to phosphorylation of membrane proteins in vitro. FEBS Lett. 1986 Mar 31;198(2):203–207. doi: 10.1016/0014-5793(86)80405-7. [DOI] [PubMed] [Google Scholar]
  19. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  20. Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. The structure, expression, and properties of additional members of the protein kinase C family. J Biol Chem. 1988 May 15;263(14):6927–6932. [PubMed] [Google Scholar]
  21. Quilliam L. A., Dobson P. R., Brown B. L. Modulation of cyclic AMP accumulation in GH3 cells by a phorbol ester and thyroliberin. Biochem Biophys Res Commun. 1985 Jun 28;129(3):898–903. doi: 10.1016/0006-291x(85)91976-x. [DOI] [PubMed] [Google Scholar]
  22. Ramsdell J. S., Pettit G. R., Tashjian A. H., Jr Three activators of protein kinase C, bryostatins, dioleins, and phorbol esters, show differing specificities of action on GH4 pituitary cells. J Biol Chem. 1986 Dec 25;261(36):17073–17080. [PubMed] [Google Scholar]
  23. Ribeiro-Neto F., Mattera R., Grenet D., Sekura R. D., Birnbaumer L., Field J. B. Adenosine diphosphate ribosylation of G proteins by pertussis and cholera toxin in isolated membranes. Different requirements for and effects of guanine nucleotides and Mg2+. Mol Endocrinol. 1987 Jul;1(7):472–481. doi: 10.1210/mend-1-7-472. [DOI] [PubMed] [Google Scholar]
  24. Salomon Y., Londos C., Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem. 1974 Apr;58(2):541–548. doi: 10.1016/0003-2697(74)90222-x. [DOI] [PubMed] [Google Scholar]
  25. Seamon K. B., Daly J. W. High-affinity binding of forskolin to rat brain membranes. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1985;19:125–135. [PubMed] [Google Scholar]
  26. Sibley D. R., Lefkowitz R. J. Molecular mechanisms of receptor desensitization using the beta-adrenergic receptor-coupled adenylate cyclase system as a model. Nature. 1985 Sep 12;317(6033):124–129. doi: 10.1038/317124a0. [DOI] [PubMed] [Google Scholar]
  27. Sibley D. R., Nambi P., Peters J. R., Lefkowitz R. J. Phorbol diesters promote beta-adrenergic receptor phosphorylation and adenylate cyclase desensitization in duck erythrocytes. Biochem Biophys Res Commun. 1984 Jun 29;121(3):973–979. doi: 10.1016/0006-291x(84)90772-1. [DOI] [PubMed] [Google Scholar]
  28. Summers S. T., Cronin M. J. Phorbol esters enhance basal and stimulated adenylate cyclase activity in a pituitary cell line. Biochem Biophys Res Commun. 1986 Feb 26;135(1):276–281. doi: 10.1016/0006-291x(86)90973-3. [DOI] [PubMed] [Google Scholar]
  29. Sutton C. A., Martin T. F. Thyrotropin-releasing hormone (TRH) selectively and rapidly stimulates phosphatidylinositol turnover in GH pituitary cells: a possible second step of TRH action. Endocrinology. 1982 Apr;110(4):1273–1280. doi: 10.1210/endo-110-4-1273. [DOI] [PubMed] [Google Scholar]
  30. Wojcikiewicz R. J., Dobson P. R., Brown B. L. Muscarinic acetylcholine receptor activation causes inhibition of cyclic AMP accumulation, prolactin and growth hormone secretion in GH3 rat anterior pituitary tumour cells. Biochim Biophys Acta. 1984 Sep 14;805(1):25–29. doi: 10.1016/0167-4889(84)90032-6. [DOI] [PubMed] [Google Scholar]
  31. Wojcikiewicz R. J., Dobson P. R., Irons L. I., Robinson A., Brown B. L. The relationship between pertussis-toxin-induced ADP-ribosylation of a plasma-membrane protein and reversal of muscarinic inhibition of prolactin secretion in GH3 cells. Biochem J. 1984 Nov 15;224(1):339–342. doi: 10.1042/bj2240339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yamashita A., Kurokawa T., Higashi K., Dan'ura T., Ishibashi S. Forskolin stabilizes a functionally coupled state between activated guanine nucleotide-binding stimulatory regulatory protein, Ns, and catalytic protein of adenylate cyclase system in rat erythrocytes. Biochem Biophys Res Commun. 1986 May 29;137(1):190–194. doi: 10.1016/0006-291x(86)91194-0. [DOI] [PubMed] [Google Scholar]
  33. Yoshimasa T., Sibley D. R., Bouvier M., Lefkowitz R. J., Caron M. G. Cross-talk between cellular signalling pathways suggested by phorbol-ester-induced adenylate cyclase phosphorylation. Nature. 1987 May 7;327(6117):67–70. doi: 10.1038/327067a0. [DOI] [PubMed] [Google Scholar]

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