Skip to main content
SpringerLink
Log in

The Role of C-type Protein Kinases in Apoptosis

  • Chapter
Apoptosis and Its Modulation by Drugs

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 142))

  • 152 Accesses

Abstract

C-type protein kinases (PKCs) mediate a multitude of signal transduction pathways triggered by phospholipid hydrolysis. Diacylglycerol is the main activator of PKCs, in addition to the modulation by Ca2+ of conventional PKC isozymes. The hydrolysis of phosphatidylinositol biphosphate by its specific phosphodiesterase provides both activators diacylglycerol and Ca2+ since inositol triphosphate releases Ca2+ from an intracellular, non-mitochondrial, calcium pool.

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

Access this chapter

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 349.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 449.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 449.99
Price excludes VAT (USA)
  • Durable hardcover 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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adachi S, Kubota M, Matsubara K, Wakazono Y, Hirota H, Kuwakado K, Akiyama Y, Mikawa H (1993) Role of protein kinase c in neutrophil survival enhanced by granulocyte colony-stimulating factor. Exp Hematol 21:1709–1713

    PubMed  CAS  Google Scholar 

  • Alessenko AV, Boikov PY, Filippova GN, Khrenov AV, Loginov AS, Makarieva ED (1997) Mechanisms of cycloheximide induced apoptosis in liver cells. FEBS Lett 416:113–116

    Article  PubMed  CAS  Google Scholar 

  • Aroor AR, Baker RC (1997) Ethanol-induced apoptosis in human HL-60 cells. Life Sci 61:2345–2350

    Article  PubMed  CAS  Google Scholar 

  • Baffy G, Miyashita T, Williamson JR, Reed JC (1993) Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. J Biol Chem 268:6511–6519

    PubMed  CAS  Google Scholar 

  • Bartek J, Bartova J, Lukas J (1996) The retinoblastoma protein and the restriction point. Curr Opin Cell Biol 8:805–814

    Article  PubMed  CAS  Google Scholar 

  • Bonnefoyberard N, Genestier L, Flacher M, Revillard JP (1994) The phosphoprotein phosphatase calcineurin controls calcium-dependent apoptosis in B cell lines. Eur J Immunol 24:325–329

    Article  CAS  Google Scholar 

  • Buttyan R, Zakeri Z, Lockshin R, Wogelmuth D (1988) Cascade induction of c-fos, cmyc and heat shock 70 K transcripts during the regression of the ventral prostate glan. Mol Endocrinol 2:650–657

    Article  PubMed  CAS  Google Scholar 

  • Chen Q, Turner J, Watson AJ, Dive C (1997) v-Abl protein tyrosine kinase (PTK) mediated suppression of apoptosis is associated with the up-regulation of Bcl-XL. Oncogene 15:2249–2254

    Article  PubMed  CAS  Google Scholar 

  • Clark W, Gillespie DA (1997) Transformation by v-Jun prevents cell cycle exit and promotes apoptosis in the absence of serum growth factors. Cell Growth Differ 8:371–380

    PubMed  CAS  Google Scholar 

  • Clarke AR, Purdie CA, Harrison DJ, Morris RG, Bird CC, Hooper ML, Wyllie AH (1993) Thymocyte apoptosis is induced by p53-dependent and independent pathways Nature 362:849–852

    Article  PubMed  CAS  Google Scholar 

  • Couldwell WT, Hinton DR, He SK, Chen TC, Sebat I, Weiss MH, Law RE (1994) Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines FEBS Lett 345:43–46

    Article  PubMed  CAS  Google Scholar 

  • Cuvillier O, Pirianov G, Kleuser B, Vanek PG, Coso OA, Gutkind JS, Spiegel S (1996) Suppression of ceramide-mediated programmed cell death by sphingosine-1phosphate. Nature 381:800–803

    Article  PubMed  CAS  Google Scholar 

  • Cryns VL, Byun Y, Rana A, Mellor H, Lustig KD, Ghanem L, Parker PJ, Kirschner MW, Yuan J (1997) Specific proteolysis of the kinase protein kinase C-related kinase 2 by caspase-3 during apoptosis. Identification by a novel, small pool expression cloning strategy. J Biol Chem 272:29449–29453

    Article  PubMed  CAS  Google Scholar 

  • Davis PK, Dudek SM, Johnson VW (1997) Select alterations in protein kinases and phosphatases during apoptosis of differentiated PC12 cells. J Neurochem 68:2338–2347

    Article  PubMed  CAS  Google Scholar 

  • Dobrowsky RT, Hannun YA (1992) Ceramide stimulates a cytosolic protein phosphatase. J Biol Chem 267:5048–5051

    PubMed  CAS  Google Scholar 

  • El Deiry WS, Tokino T, Velculescu VE et al. (1993) WAFl, a potential mediator of p53 tumor suppression. Cell 75:817–825

    Article  PubMed  Google Scholar 

  • Elledge SJ (1996) Cell cycle check points: preventing an identity crisis. Science 274:1664–1672

    Article  PubMed  CAS  Google Scholar 

  • Fesus L, Davies PJA, Piacentini M (1991) Apoptosis: molecular mechanisms in programmed cell death. Eur J Cell Biol 56:170–177

    PubMed  CAS  Google Scholar 

  • Golstein P, Ojcius DM, Young JDE (1991) Cell death mechanisms and the immune system. Immunol Rev 121:29–65

    Article  PubMed  CAS  Google Scholar 

  • Gomez J, Delahera A, Silva A, Pitton C, Garcia A, Rebollo A (1994) Implication of protein kinase C in IL-2-mediated proliferation and apoptosis in a murine T cell clone. Exp Cell Res 213:178–182

    Article  PubMed  CAS  Google Scholar 

  • Green DR, Scott DW (1994) Activation-induced apoptosis in lymphocytes. Curr Opin Immunol 6:476–487

    Article  PubMed  CAS  Google Scholar 

  • Gubina E, Rinaudo MS, Szallasi Z, Blumberg PM, Mufson RA (1998) Overexpression of protein kinase C isoform epsilon but not delta in human interleukin-3dependent cells suppresses apoptosis and induces bcl-2 expression. Blood 91:823–829

    PubMed  CAS  Google Scholar 

  • Haimovitz-Friedman A, Balaban N, Mcloughlin M, Ehleiter D, Michaeli J, Vlodavsky I, Fuks Z (1994a) Protein kinase C mediates basic fibroblast growth factor protection of endothelial cells against radiation-induced apoptosis. Cancer Res 54:2591–2597

    PubMed  CAS  Google Scholar 

  • Haimovitz-Friedman A, Kan CC, Ehleiter D, Persaud RS, Mcloughlin M, Fuks Z, Kolesnick RN (1994b) Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 180:525–535

    Article  PubMed  CAS  Google Scholar 

  • Haimovitz-Friedman A, Kolesnick RN, Fuks Z (1997) Ceramide signaling in apoptosis. Br Med Bull 53:539–553

    Article  PubMed  CAS  Google Scholar 

  • Havlicek L, Hanus J, Vesely J, Leclerc S, Meijer L, Shaw G, Strand M (1997) Cytokininderived cyclin-dependent kinase inhibitors: synthesis and cdc2 inhibitory activity of olomoucine and related compounds. J Med Chem 40:408–412

    Article  PubMed  CAS  Google Scholar 

  • Hannun YA, Linardic CM (1993) Sphingolipid breakdown products: anti-proliferative and tumor-suppressor lipids. Biochim Biophys Acta 1154:223–236

    Article  PubMed  CAS  Google Scholar 

  • Heald R, MaLoughlin M, McKeon F (1993) Human Weel maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. Cell 74:463–474

    Article  PubMed  CAS  Google Scholar 

  • Hockenberry D, Núñez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334–336

    Article  Google Scholar 

  • Iseki R, Kudo Y, Iwata M (1993) Early mobilization of Ca2+ is not required for glucocorticoid-induced apoptosis in thymocytes. J Immunol 151:5198–5207

    PubMed  CAS  Google Scholar 

  • Jacobson MD, Burne JF, King MP, Miyashita T, Reed JC, Raff MC (1993) Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature 361:365–369

    Article  PubMed  CAS  Google Scholar 

  • Jarvis WD, Kolesnick RN, Fornari FA, Traylor RS, Gerwitz DA, Grant S (1994) Induction of apoptotic DNA damage and cell death by activation of the sphingomyelin pathway. Proc Natl Acad Sci USA 91:73–77

    Article  PubMed  CAS  Google Scholar 

  • Jarvis WD, Fornari FA Jr, Auer KL, Fremerman AJ, Szabo E, Birrer MJ, Johnson CR, Barbour SE, Dent P, Grant S (1997) Coordinate regulation of stress-and mitogenactivated protein kinases in the apoptotic actions of ceramide and sphingosine. Mol Pharmacol 52:935–947

    PubMed  CAS  Google Scholar 

  • Kaneko Y, Tsukamoto A (1994) Thapsigargin-induced persistent intracellular calcium pool depletion and apoptosis in human hepatoma cells. Cancer Lett 79:147–155

    Article  PubMed  CAS  Google Scholar 

  • Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  PubMed  CAS  Google Scholar 

  • King RW, Deshaies RJ, Peters JM, Kirschner MW (1996) How proteolysis drives cell cycle. Science 274:1652–1659

    Article  PubMed  CAS  Google Scholar 

  • Knox KA, Honson GD, Gordon J (1993) Distribution of cAMP in secondary follicles and its expression in B cell apoptosis and CD40-mediated survival. Int Immunol 5:1085–1091

    Article  PubMed  CAS  Google Scholar 

  • Knox KA, Gordon J (1994) Protein tyrosine kinases couple the surface immunoglobulin of germinal center b cells to phosphatidyl inositol-dependent and independent pathways of rescue from apoptosis. Cell Immunol 155:62–76

    Article  PubMed  CAS  Google Scholar 

  • Lam M, Dubyak G, Chen L, Nuñez G, Miesfeld RL, Distelhorst CW (1994) Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. Proc Natl Acad Sci USA 91:6569–6573

    Article  PubMed  CAS  Google Scholar 

  • Liu ZG, Hsu H, Goeddel DV et al. (1996) Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-κB activation prevents cell death. Cell 87:565–576

    Article  PubMed  CAS  Google Scholar 

  • Lock RB, Thompson BS, Sullivan DM, Stribinskiene L (1997) Potentiation of etoposide-induced apoptosis by staurosporine in human tumor cells is associated with events downstream of DNA-protein complex formation. Cancer Chemother Pharmacol 39:399–409

    Article  PubMed  CAS  Google Scholar 

  • Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes Nature 362:847–849

    Article  PubMed  CAS  Google Scholar 

  • Lu Z, Liu D, Hornia A, Devonish W, Pagano M, Foster DA (1998) Activation of protein kinase C triggers its ubiquitination and degradation. Mol Cell Biol 18:839–845

    PubMed  CAS  Google Scholar 

  • Lucas M, Solano F, Sanz A (1991) Induction of programmed cell death (apoptosis) in mature lymphocytes. FEBS Lett 1:19–20

    Article  Google Scholar 

  • Lucas M, Sánchez-Margalet V, Sanz A, Solano F (1994) Protein kinase C activation promotes cell survival in mature lymphocytes prone to apoptosis. Biochem Pharmacol 47:667–672

    Article  PubMed  CAS  Google Scholar 

  • May WS, Tyler PG, Armstrong DK, Davidson NE (1993) Roll for serine phosphorylation of Bcl-2 in an antiapoptotic signaling pathway triggered by IL-3, EPO and bryostatin. Blood 82:(Suppl 1) 1738

    Google Scholar 

  • McConkey DJ, Orrenius S, Jondal M (1990) Cellular signaling in programmed cell death (apoptosis). Immunol Today 11:120–121

    Article  PubMed  CAS  Google Scholar 

  • Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N, Inagaki M, Delcros JG, Moulinoux JP (1997) Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem 243:527–536

    Article  PubMed  CAS  Google Scholar 

  • Meikrantz W, Gisselbrecht S, Tarn SW, Schlegel R (1994) Activation of cyclin a-dependent protein kinases during apoptosis. Proc Natl Acad Sci USA 91:3754–3758

    Article  PubMed  CAS  Google Scholar 

  • Migliorati G, Nicoletti I, D’Adamio F, Spreca A, Pagliacci C, Riccardi C (1994) Dexamethasone induces apoptosis in mouse natural killer cells and cytotoxic T lymphocytes. Immunology 81:21–26

    PubMed  CAS  Google Scholar 

  • Montero M, García-Sancho J, Alvarez J (1993) Transient inhibition by chemotactic peptide of a store-operated Ca2+ entry pathway in human neutrophils. J Biol Chem 268:13055–13061

    PubMed  CAS  Google Scholar 

  • Munchmore SW, Sattler M, Liang H et al. (1996) X-ray and NMR structure of human Bcl-XL, an inhibitor of programmed cell death. Nature 381:225–241

    Google Scholar 

  • Murata M, Nagai M, Fujita M, Ohmori M, Takahara J (1997) Calphostin C synergistically induces apoptosis with VP,16 in lymphoma cells which express abundant phosphorylated Bcl-2 protein. Cell Mol Life Sci 53:737–743

    Article  PubMed  CAS  Google Scholar 

  • Murray NR, Fields AP (1997) A typical protein kinase C iota protects human leukemia cells against drug-induced apoptosis. J Biol Chem 272:27521–27524

    Article  PubMed  CAS  Google Scholar 

  • Newton AC (1997) Regulation of protein kinase C. Curr Opin Cell Biol 9:161–167

    Article  PubMed  CAS  Google Scholar 

  • Nurse P (1990) Universal control mechanism regulating onset of M-phase. Nature 344:503–509

    Article  PubMed  CAS  Google Scholar 

  • Obeid LM, Linardic CM, Karolak LA, Hannun YA (1993) Programmed cell death induced by ceramide. Science 259:1769–1771

    Article  PubMed  CAS  Google Scholar 

  • Oberhammer FA, Hochegger K, Froschl G (1994) Chromatin condensation during apoptosis is accompanied by degradation of lamin A + B without activation of cdc2 kinase. J Cell Biol 126:827–837

    Article  PubMed  CAS  Google Scholar 

  • O’Brian CA (1998) Protein kinase C-alpha: a novel target for the therapy of androgen-independent prostate cancer. Oncol Rep 5:305–309

    PubMed  Google Scholar 

  • Radford IR (1994) Phorbol esters can protect mouse pre-t cell lines from radiation-induced rapid interphase apoptosis. Int J Radiat Biol 65:345–355

    Article  PubMed  CAS  Google Scholar 

  • Sánchez V, Lucas M, Sanz A, Goberna R (1992) Decreases protein kinase C activity is associated with programmed cell death (apoptosis) in freshly isolated rat hepatocytes. Biosc Report 12:199–206

    Article  Google Scholar 

  • Sánchez V, Lucas M, Solano F, Goberna R (1993) Sensitivity of insulin-secreting RIN m5F cells to undergoing apoptosis by the protein kinase C inhibitor staurosporine. Exp Cell Res 209:160–163

    Article  Google Scholar 

  • Shao RG, Shimizu T, Pommier Y (1997a) 7-Hydroxystaurosporine induces apoptosis in human colon carcinoma and leukemia cells independently of p53. Exp Cell Res 234:388–397

    Article  PubMed  CAS  Google Scholar 

  • Shao RG, Cao CX, Pommier Y (1997b) Activation of PKCalpha downstream from caspases during apoptosis induced by 7-hydroxystaurosporine or the topoisomerase inhibitors, camptothecin and etoposide, in human myeloid leukemia HL60 cells. J Biol Chem 272:31321–31325

    Article  PubMed  CAS  Google Scholar 

  • Shen SC, Huang TS, Jee SH, Kuo ML (1998) Taxol-induced p34cdc2 kinase activation and apoptosis inhibited by 12-O-tetradecanoylphorbol-13-acetate in human breast MCF-7 carcinoma cells. Cell Growth Differ 9:23–29

    PubMed  CAS  Google Scholar 

  • Shen L, Glacer IR (1998) Induction of apoptosis in gliobastoma cells by inhibition of protein kinase C and its association with the rapid accumulation of p53 and induction of the insulin-like growth factor-1-binding protein-3. Biochem Pharmacol 55:1711–1719

    Article  PubMed  CAS  Google Scholar 

  • Shi L, Nishioka WK, Th'ng J, Bradbury EM, Litchfield DW, Greenberg AH (1994) Premature p34cdc2 activation required for apoptosis. Science 263:1143–1145

    Article  PubMed  CAS  Google Scholar 

  • Spiegel S, Foster D, Kolesnick R (1996) Signal transduction through lipid second messengers. Curr Opin Cell Biol 8:159–167

    Article  PubMed  CAS  Google Scholar 

  • Thornberry NA (1996) The caspase family of cysteine proteases. British Med Bull 53:478–490

    Article  Google Scholar 

  • Tsushima H, Urata Y, Miyazaki Y, Fuchigami K, Kuriyama K, Kondo T, Tomonaga M (1997) Human erythropoietin receptor increases GATA-2 and Bcl-xL by a protein kinase C-dependent pathway in human erythropoietin-dependent cell line AS-E2. Cell Growth Differ 8:1317–1328

    PubMed  CAS  Google Scholar 

  • Wang S, Vrana JA, Bartimole TM, Freemerman AJ, Jarvis WD, Kramer LB, Krystal G, Dent P, Grant S (1997) Agents that down-regulate or inhibit protein kinase C circumvent resistance to l-beta-D-arabinofuranosylcytosine-induced apoptosis in human leukemia cells that overexpress Bcl-2. Mol Pharmacol 52:1000–1009

    PubMed  CAS  Google Scholar 

  • Wright SC, Zhong J, Larrick JW (1994) Inhibition of apoptosis as a mechanism of tumor promotion FASEB J 8:654–6

    PubMed  CAS  Google Scholar 

  • Wyllie AH, Kerr JFR, Currie AR (1980). Cell death: the significance of of apoptosis. Int Rev Cytol 68:251–356

    Article  PubMed  CAS  Google Scholar 

  • Wyllie AH (1997) Apoptosis: an overview. British Med Bull 53:451–465

    Article  CAS  Google Scholar 

  • Yoshida M, Usui T, Tsujimura K, Inagaki M, Beppu T, Horinouchi S (1997) Biochemical differences between staurosporine-induced apoptosis and premature mitosis. Exp Cell Res 232:225–239

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. M. Lucas
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pathology Toronto Hospital, General Division, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, Canada, M5G 2C4

    Ross G. Cameron M.D., Ph.D.

  2. Banting Institute Department of Clinical Biochemistry, University of Toronto, Toronto, Ontario, Canada, M5G 2C4

    George Feuer Ph.D., C. Med. Sci.

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Lucas, M. (2000). The Role of C-type Protein Kinases in Apoptosis. In: Cameron, R.G., Feuer, G. (eds) Apoptosis and Its Modulation by Drugs. Handbook of Experimental Pharmacology, vol 142. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57075-9_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-57075-9_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63025-5

  • Online ISBN: 978-3-642-57075-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation