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K. Kiss Department of Medical Biology, Medical School, University of Pécs Szigeti u. 12, H-7624 Pécs, Hungary

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Sz. Salamon Department of Medical Biology, Medical School, University of Pécs Szigeti u. 12, H-7624 Pécs, Hungary

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B. Törőcsik Department of Medical Biology, Medical School, University of Pécs Szigeti u. 12, H-7624 Pécs, Hungary

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J. Szeberényi Department of Medical Biology, Medical School, University of Pécs Szigeti u. 12, H-7624 Pécs, Hungary

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The PC12 phaeochromocytoma cell line provides a useful model to study nerve growth factor-induced neuronal differentiation. The central signaling route of this process is mediated by the Ras-dependent extracellular signal-regulated kinase cascade. However, Ras-independent pathways are also stimulated by nerve growth factor and may contribute to differentiation signaling. One mediator for Ras-independent signal transduction in PC12 cells is phospholipase C-g that generates the second messengers diacylglycerol and inositol-trisphosphate. To probe the possible involvement of this enzyme in nerve growth factor-promoted differentiation, we used the phospholipase C inhibitor U73122 and the inositol-trisphosphate-receptor inhibitor Xestospongin C. Our results show that both chemicals block nerve growth factor-promoted neurite outgrowth, but the blockage of phospholipase C does not inhibit nerve growth factor-induced expression of c-fos, zif268 and transin genes. In addition, induction of these genes by nerve growth factor plus dibutyryl-cAMP is comparable in wild-type PC12 cells as well as in cells in which both Ras- and phospholipase C-g-mediated pathways are inhibited. The phospholipase C-g pathway thus belongs to those nerve growth factor receptor-originated signaling routes that contribute to the biological response of PC12 cells to nerve growth factor, but its gene activating potential does not have a major role in its neuritogenic effect.

  • Bae, S. S., Lee, Y. H., Chang, J. S., Galadary, S. H., Kim, Y. S., Ryu, S. H., Suh, P. G. (1998) Src homology domains of phospholipase C-γ1 inhibit nerve growth factor-induced differentiation of PC12 cells. J. Neurochem. 71, 178-185.

    'Src homology domains of phospholipase C-γ1 inhibit nerve growth factor-induced differentiation of PC12 cells ' () 71 J. Neurochem : 178 -185 .

    • Search Google Scholar
  • Spivak-Kroizman, T., Mohammadi, M., Hu, P., Jaye, M., Schlessinger, J., Lax, I. (1994) Point mutation in the fibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronal differentiation of PC12 cells. J. Biol. Chem.269, 14419-14423.

    'Point mutation in the fibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronal differentiation of PC12 cells ' () 269 J. Biol. Chem. : 14419 -14423 .

    • Search Google Scholar
  • Szeberényi, J., Cai, H., Cooper, G. M. (1990) Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells. Mol. Cell. Biol.10, 5324-5332.

    'Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells ' () 10 Mol. Cell. Biol. : 5324 -5332 .

    • Search Google Scholar
  • Blumberg, D., Radeke, M. J., Feinstein, S. C. (1995) Specificity of nerve growth factor signaling: differential patterns of early tyrosine phosphorylation events induced by NGF, EGF, and bFGF. J. Neurosci Res.41, 628-639.

    'Specificity of nerve growth factor signaling: differential patterns of early tyrosine phosphorylation events induced by NGF, EGF, and bFGF ' () 41 J. Neurosci Res. : 628 -639 .

    • Search Google Scholar
  • Boglári, G., Szeberényi, J. (2001) Nerve growth factor in combination with second messenger analogues causes neuronal differentiation of PC12 cells expressing a dominant inhibitory Ras protein without inducing activation of extracellular signal-regulated kinases. Eur. J. Neurosci.14, 1445-1454.

    'Nerve growth factor in combination with second messenger analogues causes neuronal differentiation of PC12 cells expressing a dominant inhibitory Ras protein without inducing activation of extracellular signal-regulated kinases ' () 14 Eur. J. Neurosci. : 1445 -1454 .

    • Search Google Scholar
  • Carter, A. N., Downes, C. P. (1992) Phosphatidylinositol 3-kinase is activated by nerve growth factor and epidermal growth factor in PC12 cells. J. Biol. Chem.267, 14563-14567.

    'Phosphatidylinositol 3-kinase is activated by nerve growth factor and epidermal growth factor in PC12 cells ' () 267 J. Biol. Chem. : 14563 -14567 .

    • Search Google Scholar
  • Foehr, E. D., Tatavos, A., Tanabe, E., Raffioni, S., Goetz, S., Dimarco, E., De Luca, M., Bradshow, R. A. (2000) Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamem-brane domains in PDGFR/DDR/TrkA chimeric receptors. FASEB J. 14, 973-981.

    'Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamem-brane domains in PDGFR/DDR/TrkA chimeric receptors ' () 14 FASEB J : 973 -981 .

    • Search Google Scholar
  • Foehr, E. D., Raffioni, S., Murray-Rust, J., Bradshow, R. A. (2001) The role of tyrosine residues in fibroblast growth factor receptor 1 signaling. Systematic site-directed mutagenesis in the endodomain. J. Biol. Chem.276, 37529-37536.

    'The role of tyrosine residues in fibroblast growth factor receptor 1 signaling. Systematic site-directed mutagenesis in the endodomain ' () 276 J. Biol. Chem. : 37529 -37536 .

    • Search Google Scholar
  • Greene, L. A., Tischler, A. S. (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which responds to nerve growth factor. Proc. Natl. Acad. Sci. USA.73, 2424-2428.

    'Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which responds to nerve growth factor ' () 73 Proc. Natl. Acad. Sci. USA. : 2424 -2428 .

    • Search Google Scholar
  • Huang, E. J., Reichardt, L. F. (2003) Trk receptors: roles in neuronal signal transduction. Annu. Rev. Biochem.72, 609-642.

    'Trk receptors: roles in neuronal signal transduction ' () 72 Annu. Rev. Biochem. : 609 -642 .

    • Search Google Scholar
  • Kim, U. H., Fink, D. Jr, Kim, H. S., Park, D. J., Contreras, M. L., Guroff, G., Rhee, S. G. (1991) Nerve growth factor stimulates phosphorylation of phospholipase C-γ in PC12 cells. J. Biol. Chem.266, 1359-1362.

    'Nerve growth factor stimulates phosphorylation of phospholipase C-γ in PC12 cells ' () 266 J. Biol. Chem. : 1359 -1362 .

    • Search Google Scholar
  • Loeb, D. M., Stephens, R. M., Copeland, T., Kaplan, D. R., Greene, L. A. (1994) A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-γ1 abolishes NGF-promoted peripherin induction but not neurite outgrowth. J. Biol. Chem.269, 8901-8910.

    'A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-γ1 abolishes NGF-promoted peripherin induction but not neurite outgrowth ' () 269 J. Biol. Chem. : 8901 -8910 .

    • Search Google Scholar
  • Marshall, C. J. (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell80, 179-185.

    'Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation ' () 80 Cell : 179 -185 .

    • Search Google Scholar
  • McMahon, S. B., Monroe, J. G. (1992) Role of primary response genes in generating cellular responses to growth factors. FASEB J.6, 2707-2715.

    'Role of primary response genes in generating cellular responses to growth factors ' () 6 FASEB J. : 2707 -2715 .

    • Search Google Scholar
  • Obermeier, A., Bradshow, R. A., Seedorf, K., Choidas, A., Schlessinger, J., Ullrich, A. (1994) Neuronal differentiation signals are controlled by nerve growth factor receptor/Trk binding sites for SHC and PLC-γ. EMBO. J.13, 1585-1590.

    'Neuronal differentiation signals are controlled by nerve growth factor receptor/Trk binding sites for SHC and PLC-γ ' () 13 EMBO. J. : 1585 -1590 .

    • Search Google Scholar
  • Pap, M., Szeberényi, J. (1998) Differential Ras-dependence of gene induction by nerve growth factor and second messenger analogs in PC12 cells. Neurochem. Res.7, 971-977.

    'Differential Ras-dependence of gene induction by nerve growth factor and second messenger analogs in PC12 cells ' () 7 Neurochem. Res. : 971 -977 .

    • Search Google Scholar
  • Szeberényi, J., Erhardt, P., Cai, H., Cooper, G. M. (1992) Role of Ras in signal transduction from the nerve growth factor receptor: relationship to protein kinase C, calcium and cyclic AMP. Oncogene7, 2105-2113.

    'Role of Ras in signal transduction from the nerve growth factor receptor: relationship to protein kinase C, calcium and cyclic AMP ' () 7 Oncogene : 2105 -2113 .

    • Search Google Scholar
  • Szeberényi, J., Erhardt, P. (1994) Cellular components of nerve growth factor signaling. Biochim. Biophys. Acta. 1222, 187-202.

    'Cellular components of nerve growth factor signaling ' () 1222 Biochim. Biophys. Acta : 187 -202 .

    • Search Google Scholar
  • Thomas, S. M., De Marco, M., D'Arcangelo, G., Halegoua, S., Brugge, J. S. (1992) Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases. Cell68, 1031-1040.

    'Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases ' () 68 Cell : 1031 -1040 .

    • Search Google Scholar
  • Peng, X., Greene, L., Kaplan, D., Stephens, R. (1995) Deletion of a conserved juxtamembrane sequience in Trk abolishes NGF-promoted neuritogenesis. Neuron15, 395-406.

    'Deletion of a conserved juxtamembrane sequience in Trk abolishes NGF-promoted neuritogenesis ' () 15 Neuron : 395 -406 .

    • Search Google Scholar
  • Rabin, S., Cleghorn, V., Kaplan, D. (1993) SNT, a differentiation-specific target of neurotrophic factor-induced tyrosine kinase activity in neurons and PC12 cells. Mol. Cell. Biol.13, 2203-2213.

    'SNT, a differentiation-specific target of neurotrophic factor-induced tyrosine kinase activity in neurons and PC12 cells ' () 13 Mol. Cell. Biol. : 2203 -2213 .

    • Search Google Scholar
  • Soltoff, S. P., Rabin, S. L., Cantley, L. C., Kaplan, D. R. (1992) Nerve growth factor promotes the activation of phosphatidylinositol 3-kinase and its association with the trk tyrosine kinase. J. Biol. Chem.267, 17472-17477.

    'Nerve growth factor promotes the activation of phosphatidylinositol 3-kinase and its association with the trk tyrosine kinase ' () 267 J. Biol. Chem. : 17472 -17477 .

    • Search Google Scholar
  • Vetter, M. L., Bishop, J. M. (1995) b PDGF receptor mutants defective for mitogenesis promote neurite outgrowth in PC12 cells. Curr. Biol.5, 168-178.

    'b PDGF receptor mutants defective for mitogenesis promote neurite outgrowth in PC12 cells ' () 5 Curr. Biol. : 168 -178 .

    • Search Google Scholar
  • Wood, K. W., Sarnecki, C., Roberts, T. M., Blenis, J. (1992) Ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1 and RSK. Cell68, 1041-1050.

    'Ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1 and RSK ' () 68 Cell : 1041 -1050 .

    • Search Google Scholar
  • Zapf, C. A., Eichhorn, J., Webster, N. J., Olefsky, J. M. (1999) Inhibition of PLC-γ1 activity converts nerve growth factor from an anti-mitogenic to a mitogenic signal in CHO cells. Oncogene18, 4908-4919.

    'Inhibition of PLC-γ1 activity converts nerve growth factor from an anti-mitogenic to a mitogenic signal in CHO cells ' () 18 Oncogene : 4908 -4919 .

    • Search Google Scholar
  • Thompson, A., Mostafapour, S. P., Denlinger, L. C., Bleasdale, J. E., Fisher, S. K. J. (1991) The aminosteroid U-73122 inhibits muscarinic receptor sequestration and phosphoinositide hydrolysis in SK-N-SH neuroblastoma cells. A role for Gp in receptor compartmentation. J. Biol. Chem.266, 23856-23862.

    'The aminosteroid U-73122 inhibits muscarinic receptor sequestration and phosphoinositide hydrolysis in SK-N-SH neuroblastoma cells. A role for Gp in receptor compartmentation ' () 266 J. Biol. Chem. : 23856 -23862 .

    • Search Google Scholar
  • Troppmair, J., Bruder, J. T., App, H., Cai, H., Szeberényi, J., Cooper, G. M., Rapp, U. R. (1992) Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol. Oncogene7, 1867-1873.

    'Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol ' () 7 Oncogene : 1867 -1873 .

    • Search Google Scholar
  • Yao, R., Cooper, G. M. (1995) Requirement for phosphatidylinositol 3-kinase in prevention of apoptosis by nerve growth factor. Science276, 2003-2006.

    'Requirement for phosphatidylinositol 3-kinase in prevention of apoptosis by nerve growth factor ' () 276 Science : 2003 -2006 .

    • Search Google Scholar
  • Vaillancourt, R. R., Heasley, L. E., Zamarrina, J., Storey, B., Valius, M., Kazlanskas, A., Johnson, G. L. (1995) Mitogen-activated protein kinase activation is insufficient for growth factor receptor-mediated PC12 cell differentiation. Mol. Cell. Biol.15, 3644-3653.

    'Mitogen-activated protein kinase activation is insufficient for growth factor receptor-mediated PC12 cell differentiation ' () 15 Mol. Cell. Biol. : 3644 -3653 .

    • Search Google Scholar
  • Vetter, M. L., Martin, Z. D., Parada, L. F., Bishop, J. M., Kaplan, D. R. (1991) Nerve growth factor rapidly stimulates tyrosine phosphorylation of phospholipase C-γ1 by a kinase activity associated with the product of the trk protooncogene. Proc. Natl. Acad. Sci. USA88, 5650-5654.

    'Nerve growth factor rapidly stimulates tyrosine phosphorylation of phospholipase C-γ1 by a kinase activity associated with the product of the trk protooncogene ' () 88 Proc. Natl. Acad. Sci. USA : 5650 -5654 .

    • Search Google Scholar
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Editorial Board

    1. Csányi, Vilmos (Göd)
    1. Dudits, Dénes (Szeged)
    1. Falus, András (Budapest)
    1. Fischer, Ernő (Pécs)
    1. Gábriel, Róbert (Pécs)
    1. Gulya, Károly (Szeged)
    1. Gulyás, Balázs (Stockholm)
    1. Hajós, Ferenc (Budapest)
    1. Hámori, József (Budapest)
    1. Heszky, László (Gödöllő)
    1. Hideg, Éva (Szeged)
    1. E. Ito (Sanuki)
    1. Janda, Tibor (Martonvásár)
    1. Kavanaugh, Michael P. (Missoula)
    1. Kása, Péter (Szeged)
    1. Klein, Éva (Stockholm)
    1. Kovács, János (Budapest)
    1. Brigitte Mauch-Mani (Neuchâtel)
    1. Nässel, Dick R. (Stockholm)
    1. Nemcsók, János (Szeged)
    1. Péczely, Péter (Gödöllő)
    1. Roberts, D. F. (Newcastle-upon-Tyne)
    1. Sakharov, Dimitri A. (Moscow)
    1. Singh, Meharvan (Fort Worth)
    1. Sipiczky, Mátyás (Debrecen)
    1. Szeberényi, József (Pécs)
    1. Székely, György (Debrecen)
    1. Tari, Irma (Szeged)
    1. Vágvölgyi, Csaba (Szeged),
    1. L. Zaborszky (Newark)

 

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Acta Biologica Hungarica
Language English
Size  
Year of
Foundation
1950
Publication
Programme
changed title
Volumes
per Year
 
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per Year
 
Founder Magyar Tudományos Akadémia
Founder's
Address
H-1051 Budapest, Hungary, Széchenyi István tér 9.
Publisher Akadémiai Kiadó
Publisher's
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H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
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Chief Executive Officer, Akadémiai Kiadó
ISSN 0236-5383 (Print)
ISSN 1588-256X (Online)