Skip to main content
SpringerLink
Log in
Book cover

Biology of Cellular Transducing Signals pp 61–72Cite as

Mechanisms of Receptor Regulation for the Phosphoinositide Signalling System

  • Chapter

  • 46 Accesses

Abstract

It is now well established that the stimulation of certain cell surface receptors is transduced to the cell interior via the activation of phospholipase C (Putney, 1988). Most, if not all, receptors activate phospholipase C through an intermediary guanine nucleotide-dependent regulatory protein (G-protein) (Harden, 1989). Activated phospholipase C then catalyzes the breakdown of the minor membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), resulting in the generation of two intracellular messenger cascades: the inositol phosphate/Ca2+ cascade and the diacylglycerol/protein kinase C cascade. Inositol 1,4,5- trisphosphate [(1,4,5)IP3], the soluble product of PIP2 breakdown, causes the release of Ca2+ from specialized intracellular stores and initiates the process of Ca2+mobilization. Furthermore, the intracellular metabolism of (1,4,5)IP3 results in the formation of numerous soluble inositol phosphates. These may also be involved in the regulation of intracellular calcium or may have other intracellular functions. Diacylglycerol activates protein kinase C (Nishizuka, 1984), resulting in the cell specific phosphorylation of intracellular proteins.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Benovic, J.L., Regan, J.W., Matsui, H., Mayor, F., Jr., Cotecchia, S., Leeb-Lundberg, L.M.F., Caron, M.G., and Lefkowitz, R.J. (1987) Agonist-dependent phosphorylation of the α2-adrenergic receptor by the ß-adrenergic receptor kinase. J. Biol. Chem., 262:17251–17253.

    PubMed  CAS  Google Scholar 

  • Bouvier, M., Leeb-Lundberg, L.M.F., Benovic, J.L., Caron, M.G., and Lefkowitz, R.J. (1987) Regulation of adrenergic receptor function by phosphorylation. II. Effects of agonist occupancy on phosphorylation of α1- and β2-adrenergic receptors by protein kinase C and the cyclic AMP-dependent protein kinase. J. Biol. Chem., 262:3106–3113.

    PubMed  CAS  Google Scholar 

  • Cantau, B., Guillon, G., Alaoui, M.F., Chicot, D., Balestre, M.N., and Devilliers, G. (1988) Evidence of two steps in the homologous desensitization of vasopressin-sensitive phospholipase C in WRK1 cells. Uncoupling and loss of vasopressin receptors. J. Biol. Chem., 263:10443–10450.

    PubMed  CAS  Google Scholar 

  • Cooper, R.H., Coll, K.E., and Williamson, J.R. (1987) Differential effects of phorbol ester on phenylephrine and vasopressin-induced Ca2+ mobilization in isolated hepatocytes. J. Biol. Chem., 260:3281–3288.

    Google Scholar 

  • Harden, T.K. (1989) The role of guanine nucleotide regulatory proteins in receptor-selective direction of inositol lipid signalling. In: Inositol lipids in cell signalling. R.H. Michell, A.H. Drummond, and C.P. Downes, eds. Academic Press Limited, London, pp. 113–134.

    Google Scholar 

  • Hasegawa-Sasaki, H., Lutz, F., and Sasaki, T. (1988) Pathway of phospholipase C activation initiated with platelet-derived growth factor is different from that initiated with vasopressin and bombesin. J. Biol. Chem., 263:12970–12976.

    PubMed  CAS  Google Scholar 

  • Hepler, J.R., Earp, H.S., and Harden, T.K. (1988) Long-term phorbol ester treatment down-regulates protein kinase C and sensitizes the phosphoinositde signaling pathway to hormone and growth factor stimulation. J. Biol. Chem., 263:7610–7619.

    PubMed  CAS  Google Scholar 

  • Horstman, D.A., Takemura, H., and Putney, J.W., Jr. (1988) Formation and metabolism of 3H-inositol phosphates in AR42J pancreatoma cells. J. Biol. Chem., 263:15297–15303.

    PubMed  CAS  Google Scholar 

  • Kwatra, K.M., and Hosey, M.M. (1986) Phosphorylation of the cardiac muscarinic receptor in intact chick heart and its regulation by a muscarinic agonist. J. Biol. Chem., 261:12429–12432.

    PubMed  CAS  Google Scholar 

  • Kwatra, M.M., Leung, E., Maan, A.C., McMahon, K.K., Ptasienski, J., Green, R.D., and Hosey, M.M. (1987) Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J. Biol. Chem., 262:16314–16321.

    PubMed  CAS  Google Scholar 

  • Leeb-Lundberg, L.M.F., Cotecchia, S., DeBlasi, A., Caron, M.G., and Lefkowitz, R.J. (1987) Regulation of adrenergic receptor function by phosphorylation. I. Agonist-promoted desensitization and phosphorylation of α1-adrenergic receptors coupled to inositol phospholipid metabolism in DDT1 MF-2 smooth muscle cells. J. Biol. Chem., 262:3098–3105.

    PubMed  CAS  Google Scholar 

  • Lefkowitz, R.J., and Caron, M.G. (1988) Adrenergic receptors. Models for the study of receptors coupled to guanine nucleotide regulatory proteins. J. Biol. Chem., 263:4993–4996.

    PubMed  CAS  Google Scholar 

  • Liles, W.C., Hunter, D.D., Meier, K.E., and Nathanson, N.M. (1986) Activation of protein kinase C induces rapid internalization and subsequent degradation of muscarinic acetylcholine receptors in neuroblastoma cells. J. Biol. Chem., 261:5307–5313.

    PubMed  CAS  Google Scholar 

  • Mayor, F., Jr., Benovic, J.L., Caron, M.G., and Lefkowitz, R.J. (1987) Somatostatin induces translocation of the β-adrenergic receptor kinase and desensitizes somatostatin receptors in S49 lymphoma cells. J. Biol. Chem., 262:6468–6471.

    PubMed  CAS  Google Scholar 

  • McMillian, M.K., Soltoff, S.P., and Talamo, B.R. (1987) Rapid desensitization of substance P- but not carbachol-induced increases in inositol trisphosphate and intracellular Ca++ in rat parotid acinar cells. Biochem. Biophys. Res. Commun., 148:1017–1024.

    Article  PubMed  CAS  Google Scholar 

  • Morrison, W.J., and Shukla, S.D. (1988) Desensitization of receptor-coupled activation of phosphoinositide- specific phospholipase C in platelets: evidence for distinct mechanisms for platelet-activating factor and thrombin. Mol. Pharmacol., 33:58–63.

    PubMed  CAS  Google Scholar 

  • Nakahata, N., and Harden, T.K. (1987) Regulation of inositol trisphosphate accumulation by muscarinic cholinergic and H1-histamine receptors on human astrocytoma cells. Differential induction of desensitization by agonists. Biochem. J., 241: 337–344.

    PubMed  CAS  Google Scholar 

  • Nishizuka, Y. (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 308:693–698.

    Article  PubMed  CAS  Google Scholar 

  • Orellana, S., Solski, P.A., and Brown, J.H. (1987) Guanosine 5’-0-(thiophosphate)-dependent inositol trisphosphate formation in membranes is inhibited by phorbol ester and protein kinase C. J. Biol. Chem., 262:1638–1643.

    PubMed  CAS  Google Scholar 

  • Pachter, J.A., Law, G.J., and Dannies, P.S. (1988) Bombesin stimulates inositol polyphosphate production in GH4C1 pituitary tumor cells: Comparison with TRH. Biochem. Biophys. Res. Comm., 154:654–659.

    Article  PubMed  CAS  Google Scholar 

  • Paris, S., Magnaldo, I., and Pouyssegur, J. (1988) Homologous desensitization of thrombin-induced phosphoinositide breakdown in hamster lung fibroblasts. J. Biol. Chem., 263:11250–11256.

    PubMed  CAS  Google Scholar 

  • Pearce, B., Morrow, C., and Murphy, S. (1988) Characteristics of phorbol ester- and agonist-induced down-regulation of astrocyte receptors coupled to inositol phospholipid metabolism. J. Neurochem., 50:936–944.

    Article  PubMed  CAS  Google Scholar 

  • Pfeilschifter, J. (1986) Tumor promotor 12-0-tetradecanoylphorbol 13-acetate inhibits angiotensin II-induced inositol phosphate production and cytocolic Ca2+ rise in rat renal mesangial cells. FEBS Lett., 203:262–266.

    Article  PubMed  CAS  Google Scholar 

  • Pfeilschifter, J. (1988) Protein kinase C from rat renal mesangial cells: its role in homologous desensitization of angiotensin II-induced polyphosphoinositide hydrolysis. Biochim. Biophys. Acta. 969:263–270.

    Article  PubMed  CAS  Google Scholar 

  • Pfeilschifter, J., and Bauer, C. (1987) Different effects of phorbol ester on angiotensin II- and stable GTP analogue-induced activation of polyphosphoinositide phosphodiesterase in membranes isolated from rat renal mesangial cells. Biochem. J., 240:209–215.

    Google Scholar 

  • Putney, J.W., Jr. (1988) The role of phosphinositide metabolism in signal transduction in secretory cells. J. Exp. Biol., 139:135–150.

    PubMed  CAS  Google Scholar 

  • Sibley, D.R., Benovic, J.L., Caron, M.G., and Lefkowitz, R.J. (1988) Phosphorylation of cell surface receptors: a mechanism for regulating signal transduction pathways. Endocr. Rev., 9:38–56.

    Article  PubMed  CAS  Google Scholar 

  • Strasser, R.H., Benovic, J.L., Caron, M.G., and Lęfkowitz, R.J. (1986) β-agonist- and prostaglandin E1-induced translocation of the β-adrenergic receptor kinase: Evidence that the kinase may act on multiple adenylate cyclase-coupled receptors. Proc. Natl. Acad. Sci. USA. 83:6362–6366.

    Article  PubMed  CAS  Google Scholar 

  • Sugiya, H., Obie, J.F., and Putney, J.W., Jr. (1988) Two modes of regulation of the phospholipase C-linked substance P receptor in rat parotid acinar cells. Biochem. J., 253:459–446.

    PubMed  CAS  Google Scholar 

  • Sugiya, H., and Putney, J.W., Jr. (1988) Substance P receptor desensitization requires activation of receptor, but not phospholipase C. Am. J. Physiol., 255:C149–C154.

    PubMed  CAS  Google Scholar 

  • Sugiya, H., and Putney, J.W., Jr. (1988) Protein kinase C-dependent and -independent mechanisms regulating the parotid substance P receptor as revealed by differential effects of protein kinase C inhibitors. Biochem. J., 256:677–680.

    PubMed  CAS  Google Scholar 

  • Sugiya, H., Tennes, K.A., and Putney, J.W., Jr. (1987) Homologous desensitization of substance-P-induced inositol polyphosphate formation in rat parotid acinar cells. Biochem. J., 244:647–653.

    PubMed  CAS  Google Scholar 

  • Tohmatsu, T., Hattori, H., Nagao, S., Ohki, K., and Nozawa, Y. (1986) Reversal by protein kinase C inhibitor of suppressive actions of phorbol-12-myrstate-13-acetate on polyphosphoinositide metabolism and cytosolic Ca2+ mobilization in thrombin-stimulated human platelets. Biochem. Biophys. Res. Comm., 134:868–875.

    Article  PubMed  CAS  Google Scholar 

  • Torjesen, P.A., Bjoro, T., Ostberg, B.C., and Haug, E. (1988) Thyrotropin-releasing hormone-stimulated inositol trisphosphate formation is liable to thyrotropin-releasing hormone - induced desensitization by a calcium-dependent mechanism. Mol. Cell Endocrinol., 56:107–114.

    Article  PubMed  CAS  Google Scholar 

  • Vegesna, R.V., Wu, H.L., Mong, S., and Crooke, S.T. (1988) Staurosporine inhibits protein kinase C and prevents phorbol ester-mediated leukotriene D4 receptor desensitization in RBL-1 cells. Mol. Pharmacol., 33:537–542.

    PubMed  CAS  Google Scholar 

  • Winkler, J.D., Sarau, H.M., Foley, J.J., Mong, S., and Crooke, S.T. (1988) Leukotriene B4-induced homologous desensitization of calcium mobilization and phosphoinositide metabolism in U-937 cells. J. Pharmacol. Exp. Ther., 246:204–210.

    PubMed  CAS  Google Scholar 

  • Xu, J., and Chuang, D.M. (1987) Muscarinic acetylcholine receptor-mediated phosphoinositide turnover in cultured cerebellar granule cells: desensitization by receptor agonists. J. Pharmacol. Exp. Ther., 242;238–244.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA

    Frank S. Menniti, Haruo Takemura, Hiroshi Sugiya & James W. Putney Jr.

Authors
  1. Frank S. Menniti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haruo Takemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroshi Sugiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James W. Putney Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The George Washington University Medical Center, Washington, D.C., USA

    Jack Y. Vanderhoek

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Plenum Press, New York

About this chapter

Cite this chapter

Menniti, F.S., Takemura, H., Sugiya, H., Putney, J.W. (1990). Mechanisms of Receptor Regulation for the Phosphoinositide Signalling System. In: Vanderhoek, J.Y. (eds) Biology of Cellular Transducing Signals. GWUMC Department of Biochemistry Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0559-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0559-0_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-7866-5

  • Online ISBN: 978-1-4613-0559-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation