[en] We analysed how interactions between protein kinase-dependent intracellular signalling pathways were implicated in the control of the production of tissue-type plasminogen activator (tPA) and the generation of neurite outgrowth by PC12 cells. To that aim, cells were treated with agents that interact with the trk receptor and with protein kinases A and C. Nerve growth factor induced only the formation of large neurites. The release of the protease and the production of short neurite outgrowth were found to be protein-kinase-A-dependent events that could be enhanced by simultaneous activation of protein kinase C with phorbol ester. At high concentration, staurosporine, a nonselective inhibitor of protein kinases, induced the production of short neurites and mimicked the protein-kinase-A-dependent effect on tPA release. Such a response was not observed with K-252a, an analogue of staurosporine devoid of neurite-outgrowth-promoting activity. The responses to protein kinase A stimulation and the addition of staurosporine, although similar, seemed to occur through an activation of distinct, yet interacting, signalling pathways. In conclusion, tPA release and large neurite outgrowth from PC12 cells are controlled by parallel, albeit interacting, pathways, suggesting that these two potentially antagonistic events in PC12 cell differentiation can be modulated in a concerted way or independently of each other, depending on the activity of several protein kinases.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Leprince, Pierre ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.
Bonvoisin, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > Néphrologie
Rogister, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Mazy-Servais, C.
Moonen, Gustave ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie - Doyen de la Faculté de Médecine
Language :
English
Title :
Protein Kinase- and Staurosporine-Dependent Induction of Neurite Outgrowth and Plasminogen Activator Activity in Pc12 Cells
Publication date :
08 November 1996
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Elsevier, Netherlands
Volume :
52
Issue :
9
Pages :
1399-405
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] FMRE - Fondation Médicale Reine Elisabeth [BE]
1. Greene LA and Tischler AS, Establishment of a noradrenergic clonal line of rat adrenal phaeochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA 73: 2424-2428, 1976.
2. Hashimoto S, K-252a, a potent protein kinase inhibitor, blocks nerve growth factor-induced neurite outgrowth and changes in the phosphorylation of proteins in PC12h cells. J Cell Biol 107: 1531-1539, 1988.
3. Koizumi S, Contreras ML, Matsuda Y, Hama T, Lazarovici P and Guroff G, K-252a: A specific inhibitor of the action of nerve growth factor on PC12 cells. J Neurosci 8(2): 715-721, 1988.
4. Hashimoto S and Hagino A, Blockage of nerve growth factor action in PC12h cells by staurosporine, a potent protein kinase inhibitor. J Neurochem 53: 1675-1685, 1989.
5. Berg MM, Sternberg DW, Parada LF and Chao MV, K-252a inhibits nerve growth factor-induced trk proto-oncogene tyrosine phosphorylation and kinase activity. J Biol Chem 267: 13-16, 1992.
6. Ohmichi M, Decker SJ, Pang L and Saltiel AR, Inhibition of the cellular actions of nerve growth factor by staurosporine and K252a results from the attenuation of the activity of the trk tyrosine kinase. Biochemistry 31: 4034-4039, 1992.
7. Kaplan DR, Martin-Zanca D and Parada LF, Tyrosine phosphorylation and tyrosine kinase activity of the trk protooncogene product induced by NGF. Nature 350: 158-160, 1991.
8. Klein R, Jing S, Nanduri V, O'Rourke E and Barbacid M, The trk proto-oncogene encodes a receptor for nerve growth factor. Cell 65: 189-197, 1991.
9. Mann DA, Doherty P and Walsh FS, Increased intracellular cyclic AMP differentially modulates nerve growth factor induction of three neuronal recognition molecules involved in neurite outgrowth. J Neurochem 53: 1581-1588, 1989.
10. Brady MJ, Nairn AC, Wagner JA and Palfrey HC, Nerve growth factor-induced down-regulation of calmodulin-dependent protein kinase III in PC12 cells involves cyclic AMP-dependent protein kinase. J Neurochem 54: 1034-1039, 1990.
11. Cremins J, Wagner JA and Halegoua S, Nerve growth factor action is mediated by cyclic AMP- and Ca+2/phospholipid-dependent protein kinases. J Cell Biol 103: 887-893, 1986.
12. Doherty P, Mann DA and Walsh FS, Comparison of the effects of NGF, activators of protein kinase C, and a calcium ionophore on the expression of Thy-1 and N-CAM in PC12 cell cultures. J Cell Biol 107: 333-340, 1988.
13. Richter-Landsberg C and Jarstoff B, The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells. J Cell Biol 102: 821-829, 1986.
14. Ginty DD, Glowacka D, DeFranco C and Wagner JA, Nerve growth factor-induced neuronal differentiation after dominant repression of both type I and type II cAMP-dependent protein kinase activities. J Biol Chem 266: 15325-15333, 1991.
15. Sigmund O, Naor S, Anderson DJ and Stein R, Effect of nerve growth factor and fibroblast growth factor on SCG10 and c-fos expression and neurite outgrowth in protein kinase C-depleted PC12 cells. J Biol Chem 265: 2257-2261, 1990.
16. Cahill AL, Horwitz J and Perlman RL, Phosphorylation of tyrosine hydroxylase in protein kinase C-deficient PC12 cells. Neuroscience 30: 811-818, 1989.
17. Hashimoto S and Hagino A, Nerve growth factor-induced transient increase in the phosphorylation of ribosomal protein S6 mediated through a mechanism independent of cyclic AMP-dependent protein kinase and protein kinase C. J Neurochem 55: 970-980, 1990.
18. Damon DH, D'Amore PA and Wagner JA, Nerve growth factor and fibroblast growth factor regulate neurite outgrowth and gene expression in PC12 cells via both protein kinase C- and cAMP-independent mechanisms. J Cell Biol 110: 1333-1339, 1990.
19. Gunning PW, Landreth GE, Bothwell MA and Shooter EM, Differential and synergistic actions of nerve growth factor and cyclic AMP m PC12 cells. J Cell Biol 89: 240-245, 1981.
20. Heidemann SR, Joshi HC, Schechter A, Fletcher JR and Bothwell MA, Synergistic effects of cyclic AMP and nerve growth factor on neurite outgrowth and microtubule stability of PC12 cells. J Cell Biol 100: 916-927, 1985.
21. Sugimoto Y, Noda M, Kitayama H and Ikawa Y, Possible involvement of two signaling pathways in induction of neuron-associated properties by v-Ha-ras gene in PC12 cells. J Biol Chem 263 (24): 12102-12108, 1988.
22. Burstein DE, Blumberg PM and Greene LA, Nerve growth factor-induced neuronal differentiation of PC12 pheochromocytoma cells: lack of inhibition by a tumor promoter. Brain Res 247: 115-119, 1982.
23. Hashimoto S and Hagino A, Staurosporine-induced neurite outgrowth in PC12h cells. Exp Cell Res 184: 351-359, 1989.
24. Leprince P, Rogister B, Delrée P, Rigo J-M, André B and Moonen G, Modulation of proteolytic activity during neuritogenesis in the PC12 nerve cell: differential control of plasminogen activator and plasminogen activator inhibitor activities by nerve growth factor and dibutyryl-cyclic AMP. J Neurochem 57(2): 665-674, 1991.
25. Krystosek A and Seeds NW, Plasminogen activator release at the neuronal growth cone. Science 213: 1532-1534, 1981.
26. Pittman RN, Ivins JK and Buettner HM, Neuronal plasminogen activators: cell surface binding sites and involvement in neunte outgrowth. J Neurosci 9(12): 4269-4286, 1989.
27. Pittman RN and DiBenedetto AJ, PC12 cells overexpressing tissue plasminogen activator regenerate neurites to a greater extent and migrate faster than control cells in complex extracellular matrix. J Neurochem 64: 566-575, 1995.
28. Mobley WC, Schenker A and Shooter EM, Characterization and isolation of proteolytically modified nerve growth factor. Biochemistry 15: 5543-5552, 1976.
29. Leprince P, Rogister B and Moonen G, A colorimetric assay for the simultaneous measurement of plasminogen activators and plasminogen activator inhibitors in serum-free conditioned media from cultured cells. Anal Biochem 177: 341-346, 1989.
30. Lowry OH, Rosenbrough NJ, Farr AL and Randall RJ, Protein measurement with the folin phenol reagent. J Biol Chem 193: 265-275, 1951.
31. Kvanta A and Fredholm BB, Synergistic effects between protein kinase C and cAMP on activator protein-1 activity and differentiation of PC12 pheochromocytoma cells. J Mol Neurosci 4: 205-214, 1993.
32. Frödin M, Peraldi P and Van Obberghen E, Cyclic AMP activates the mitogen-activated protein kinase cascade in PC12 cells. J Biol Chem 269: 6207-6214, 1994.
33. Hollingsworth EB, Ukena D and Daly JW, The protein kinase C activator phorbol-12-myristate-13-acetate enhances cyclic AMP accumulation in pheochromocytoma cells. FEBS Lett 196: 131-134, 1986.
34. Rasouly D, Rahamim E, Lester D, Matsuda Y and Lazarovici P, Staurosporine-induced neurite outgrowth in PC12 cells is independent of protein kinase inhibition. Mol Pharmacol 42: 35-43, 1992.
35. Cheng B, Barger SW and Mattson MP, Staurosporine, K-252a, and K-252b stabilize calcium homeostasis and promote survival of CNS neurons in the absence of glucose. J Neurochem 62: 1319-1329, 1994.
36. Sadot E, Barg J, Rasouly D, Lazarovici P and Ginzburg I, Short- and long-term mechanisms of tau regulation in PC12 cells. J Cell Sci 108: 2857-2864, 1995.
37. Rasouly D and Lazarovici P, Staurosporine induces tyrosine phosphorylation of a 145 kDa protein but does not activate gp140trk in PC12 cells. Eur J Pharmacol 269: 255-264, 1994.
38. Pavlovic-Surjancev B, Cahill AL and Perlman RL, Staurosporine activates a 60,000 Mr protein kinase in bovine chromaffin cells that phosphorylates myelin basic protein in vitro. J Neurochem 61: 697-703, 1993.
39. Knüsel B and Hefti F, K-252 compounds: modulators of neurotrophin signal transduction. J Neurochem 59: 1987-1996, 1992.
40. Doherty P and Walsh FS, Cell adhesion molecules, second messengers and axonal growth. Curr Opin Neurobiol 2: 595-601, 1992.
41. Williams EJ, Walsh FS and Doherty P, The production of arachidonic acid can account for calcium channel activation in the second messenger pathway underlying neurite outgrowth stimulated by NCAM, N-cadherin, and L1. J Neurochem 62: 1231-1234, 1994.
42. Levitzki A and Gazit A, Tyrosine kinase inhibition: an approach to drug development. Science 267: 1782-1788, 1995.