Abstract
Free full text
Testing the in vivo role of protein kinase C and c-fos in neurite outgrowth by microinjection of antibodies into PC12 cells.
Abstract
To define the molecular bases of growth factor-induced signal transduction pathways, antibodies known to block the activity of either protein kinase C (PKC) or the fos protein were introduced into PC12 cells by microinjection. The antibody against PKC significantly inhibited neurite outgrowth when scored 24 h after microinjection and exposure to nerve growth factor (NGF). Microinjection of antibodies to fos significantly increased the percentage of neurite-bearing cells after exposure to either NGF or basic fibroblast growth factor (bFGF) but inhibited the stimulation of DNA synthesis by serum, suggesting that in PC12 cells, fos is involved in cellular proliferation. Thus, activation of PKC is involved in the induction of neurite outgrowth by NGF, but expression of the fos protein, which is induced by both NGF and bFGF, is not necessary and inhibits neurite outgrowth.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alemà S, Casalbore P, Agostini E, Tatò F. Differentiation of PC12 phaeochromocytoma cells induced by v-src oncogene. Nature. 1985 Aug 8;316(6028):557–559. [Abstract] [Google Scholar]
- Altin JG, Bradshaw RA. Production of 1,2-diacylglycerol in PC12 cells by nerve growth factor and basic fibroblast growth factor. J Neurochem. 1990 May;54(5):1666–1676. [Abstract] [Google Scholar]
- Altin JG, Kujubu DA, Raffioni S, Eveleth DD, Herschman HR, Bradshaw RA. Differential induction of primary-response (TIS) genes in PC12 pheochromocytoma cells and the unresponsive variant PC12nnr5. J Biol Chem. 1991 Mar 25;266(9):5401–5406. [Abstract] [Google Scholar]
- Altin JG, Wetts R, Bradshaw RA. Microinjection of a p21ras antibody into PC12 cells inhibits neurite outgrowth induced by nerve growth factor and basic fibroblast growth factor. Growth Factors. 1991;4(2):145–155. [Abstract] [Google Scholar]
- Bar-Sagi D, Feramisco JR. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation. Cell. 1985 Oct;42(3):841–848. [Abstract] [Google Scholar]
- Burstein DE, Blumberg PM, Greene LA. Nerve growth factor-induced neuronal differentiation of PC12 pheochromocytoma cells: lack of inhibition by a tumor promoter. Brain Res. 1982 Sep 9;247(1):115–119. [Abstract] [Google Scholar]
- Burstein DE, Greene LA. Evidence for RNA synthesis-dependent and -independent pathways in stimulation of neurite outgrowth by nerve growth factor. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6059–6063. [Europe PMC free article] [Abstract] [Google Scholar]
- Chiu R, Boyle WJ, Meek J, Smeal T, Hunter T, Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. [Abstract] [Google Scholar]
- Cho KO, Skarnes WC, Minsk B, Palmieri S, Jackson-Grusby L, Wagner JA. Nerve growth factor regulates gene expression by several distinct mechanisms. Mol Cell Biol. 1989 Jan;9(1):135–143. [Europe PMC free article] [Abstract] [Google Scholar]
- Cooper DR, Watson JE, Acevedo-Duncan M, Pollet RJ, Standaert ML, Farese RV. Retention of specific protein kinase C isozymes following chronic phorbol ester treatment in BC3H-1 myocytes. Biochem Biophys Res Commun. 1989 May 30;161(1):327–334. [Abstract] [Google Scholar]
- Cremins J, Wagner JA, Halegoua S. Nerve growth factor action is mediated by cyclic AMP- and Ca+2/phospholipid-dependent protein kinases. J Cell Biol. 1986 Sep;103(3):887–893. [Europe PMC free article] [Abstract] [Google Scholar]
- Curran T, Morgan JI. Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines. Science. 1985 Sep 20;229(4719):1265–1268. [Abstract] [Google Scholar]
- Damon DH, D'Amore PA, 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. 1990 Apr;110(4):1333–1339. [Europe PMC free article] [Abstract] [Google Scholar]
- Eveleth DD, Hanecak R, Fox GM, Fan H, Bradshaw RA. v-src genes stimulate neurite outgrowth in pheochromocytoma (PC12) variants unresponsive to neurotrophic factors. J Neurosci Res. 1989 Sep;24(1):67–71. [Abstract] [Google Scholar]
- Fox GM, Schiffer SG, Rohde MF, Tsai LB, Banks AR, Arakawa T. Production, biological activity, and structure of recombinant basic fibroblast growth factor and an analog with cysteine replaced by serine. J Biol Chem. 1988 Dec 5;263(34):18452–18458. [Abstract] [Google Scholar]
- Gizang-Ginsberg E, Ziff EB. Nerve growth factor regulates tyrosine hydroxylase gene transcription through a nucleoprotein complex that contains c-Fos. Genes Dev. 1990 Apr;4(4):477–491. [Abstract] [Google Scholar]
- Glowacka D, Wagner JA. Role of the cAMP-dependent protein kinase and protein kinase C in regulating the morphological differentiation of PC12 cells. J Neurosci Res. 1990 Apr;25(4):453–462. [Abstract] [Google Scholar]
- Graham R, Gilman M. Distinct protein targets for signals acting at the c-fos serum response element. Science. 1991 Jan 11;251(4990):189–192. [Abstract] [Google Scholar]
- Greene LA, Shooter EM. The nerve growth factor: biochemistry, synthesis, and mechanism of action. Annu Rev Neurosci. 1980;3:353–402. [Abstract] [Google Scholar]
- Guerrero I, Pellicer A, Burstein DE. Dissociation of c-fos from ODC expression and neuronal differentiation in a PC12 subline stably transfected with an inducible N-ras oncogene. Biochem Biophys Res Commun. 1988 Feb 15;150(3):1185–1192. [Abstract] [Google Scholar]
- Guerrero I, Wong H, Pellicer A, Burstein DE. Activated N-ras gene induces neuronal differentiation of PC12 rat pheochromocytoma cells. J Cell Physiol. 1986 Oct;129(1):71–76. [Abstract] [Google Scholar]
- Hagag N, Halegoua S, Viola M. Inhibition of growth factor-induced differentiation of PC12 cells by microinjection of antibody to ras p21. Nature. 1986 Feb 20;319(6055):680–682. [Abstract] [Google Scholar]
- Hall FL, Fernyhough P, Ishii DN, Vulliet PR. Suppression of nerve growth factor-directed neurite outgrowth in PC12 cells by sphingosine, an inhibitor of protein kinase C. J Biol Chem. 1988 Mar 25;263(9):4460–4466. [Abstract] [Google Scholar]
- Hama T, Huang KP, Guroff G. Protein kinase C as a component of a nerve growth factor-sensitive phosphorylation system in PC12 cells. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2353–2357. [Europe PMC free article] [Abstract] [Google Scholar]
- Heasley LE, Johnson GL. Regulation of protein kinase C by nerve growth factor, epidermal growth factor, and phorbol esters in PC12 pheochromocytoma cells. J Biol Chem. 1989 May 25;264(15):8646–8652. [Abstract] [Google Scholar]
- Huang M, Chida K, Kamata N, Nose K, Kato M, Homma Y, Takenawa T, Kuroki T. Enhancement of inositol phospholipid metabolism and activation of protein kinase C in ras-transformed rat fibroblasts. J Biol Chem. 1988 Dec 5;263(34):17975–17980. [Abstract] [Google Scholar]
- Hsu L, Jeng AY, Chen KY. Induction of neurite outgrowth from chick embryonic ganglia explants by activators of protein kinase C. Neurosci Lett. 1989 May 8;99(3):257–262. [Abstract] [Google Scholar]
- Ito E, Sonnenberg JL, Narayanan R. Nerve growth factor-induced differentiation in PC-12 cells is blocked by fos oncogene. Oncogene. 1989 Oct;4(10):1193–1199. [Abstract] [Google Scholar]
- Kruijer W, Schubert D, Verma IM. Induction of the proto-oncogene fos by nerve growth factor. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7330–7334. [Europe PMC free article] [Abstract] [Google Scholar]
- Lacal JC. Diacylglycerol production in Xenopus laevis oocytes after microinjection of p21ras proteins is a consequence of activation of phosphatidylcholine metabolism. Mol Cell Biol. 1990 Jan;10(1):333–340. [Europe PMC free article] [Abstract] [Google Scholar]
- Lacal JC, Moscat J, Aaronson SA. Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene. Nature. 1987 Nov 19;330(6145):269–272. [Abstract] [Google Scholar]
- Ledwith BJ, Manam S, Kraynak AR, Nichols WW, Bradley MO. Antisense-fos RNA causes partial reversion of the transformed phenotypes induced by the c-Ha-ras oncogene. Mol Cell Biol. 1990 Apr;10(4):1545–1555. [Europe PMC free article] [Abstract] [Google Scholar]
- Milbrandt J. Nerve growth factor rapidly induces c-fos mRNA in PC12 rat pheochromocytoma cells. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4789–4793. [Europe PMC free article] [Abstract] [Google Scholar]
- Mobley WC, Schenker A, Shooter EM. Characterization and isolation of proteolytically modified nerve growth factor. Biochemistry. 1976 Dec 14;15(25):5543–5552. [Abstract] [Google Scholar]
- Mochly-Rosen D, Koshland DE., Jr Domain structure and phosphorylation of protein kinase C. J Biol Chem. 1987 Feb 15;262(5):2291–2297. [Abstract] [Google Scholar]
- Mochly-Rosen D, Koshland DE., Jr A general procedure for screening inhibitory antibodies: application for identifying anti-protein kinase C antibodies. Anal Biochem. 1988 Apr;170(1):31–37. [Abstract] [Google Scholar]
- Morgan JI, Curran T. Role of ion flux in the control of c-fos expression. Nature. 1986 Aug 7;322(6079):552–555. [Abstract] [Google Scholar]
- Nichols RA, Chandler CE, Shooter EM. Enucleation of the rat pheochromocytoma clonal cell line, PC12: effect on neurite outgrowth. J Cell Physiol. 1989 Nov;141(2):301–309. [Abstract] [Google Scholar]
- Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. [Abstract] [Google Scholar]
- Rausch DM, Dickens G, Doll S, Fujita K, Koizumi S, Rudkin BB, Tocco M, Eiden LE, Guroff G. Differentiation of PC12 cells with v-src: comparison with nerve growth factor. J Neurosci Res. 1989 Sep;24(1):49–58. [Abstract] [Google Scholar]
- Reinhold DS, Neet KE. The lack of a role for protein kinase C in neurite extension and in the induction of ornithine decarboxylase by nerve growth factor in PC12 cells. J Biol Chem. 1989 Feb 25;264(6):3538–3544. [Abstract] [Google Scholar]
- Riabowol KT, Fink JS, Gilman MZ, Walsh DA, Goodman RH, Feramisco JR. The catalytic subunit of cAMP-dependent protein kinase induces expression of genes containing cAMP-responsive enhancer elements. Nature. 1988 Nov 3;336(6194):83–86. [Abstract] [Google Scholar]
- Riabowol KT, Vosatka RJ, Ziff EB, Lamb NJ, Feramisco JR. Microinjection of fos-specific antibodies blocks DNA synthesis in fibroblast cells. Mol Cell Biol. 1988 Apr;8(4):1670–1676. [Europe PMC free article] [Abstract] [Google Scholar]
- Rydel RE, Greene LA. Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells. J Neurosci. 1987 Nov;7(11):3639–3653. [Abstract] [Google Scholar]
- Sassone-Corsi P, Der CJ, Verma IM. ras-induced neuronal differentiation of PC12 cells: possible involvement of fos and jun. Mol Cell Biol. 1989 Aug;9(8):3174–3183. [Europe PMC free article] [Abstract] [Google Scholar]
- Satoh T, Nakamura S, Kaziro Y. Induction of neurite formation in PC12 cells by microinjection of proto-oncogenic Ha-ras protein preincubated with guanosine-5'-O-(3-thiotriphosphate). Mol Cell Biol. 1987 Dec;7(12):4553–4556. [Europe PMC free article] [Abstract] [Google Scholar]
- Schubert D, Ling N, Baird A. Multiple influences of a heparin-binding growth factor on neuronal development. J Cell Biol. 1987 Mar;104(3):635–643. [Europe PMC free article] [Abstract] [Google Scholar]
- Sheng M, Dougan ST, McFadden G, Greenberg ME. Calcium and growth factor pathways of c-fos transcriptional activation require distinct upstream regulatory sequences. Mol Cell Biol. 1988 Jul;8(7):2787–2796. [Europe PMC free article] [Abstract] [Google Scholar]
- Sheng M, Greenberg ME. The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron. 1990 Apr;4(4):477–485. [Abstract] [Google Scholar]
- Sheng M, McFadden G, Greenberg ME. Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB. Neuron. 1990 Apr;4(4):571–582. [Abstract] [Google Scholar]
- Sigmund O, Naor Z, Anderson DJ, 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. 1990 Feb 5;265(4):2257–2261. [Abstract] [Google Scholar]
- Stacey DW, DeGudicibus SR, Smith MR. Cellular ras activity and tumor cell proliferation. Exp Cell Res. 1987 Jul;171(1):232–242. [Abstract] [Google Scholar]
- Thomson TM, Green SH, Trotta RJ, Burstein DE, Pellicer A. Oncogene N-ras mediates selective inhibition of c-fos induction by nerve growth factor and basic fibroblast growth factor in a PC12 cell line. Mol Cell Biol. 1990 Apr;10(4):1556–1563. [Europe PMC free article] [Abstract] [Google Scholar]
- Tiercy JM, Shooter EM. Early changes in the synthesis of nuclear and cytoplasmic proteins are induced by nerve growth factor in differentiating rat PC12 cells. J Cell Biol. 1986 Dec;103(6 Pt 1):2367–2378. [Europe PMC free article] [Abstract] [Google Scholar]
- Togari A, Dickens G, Kuzuya H, Guroff G. The effect of fibroblast growth factor on PC12 cells. J Neurosci. 1985 Feb;5(2):307–316. [Abstract] [Google Scholar]
- Vosatka RJ, Hermanowski-Vosatka A, Metz R, Ziff EB. Dynamic interactions of c-fos protein in serum-stimulated 3T3 cells. J Cell Physiol. 1989 Mar;138(3):493–502. [Abstract] [Google Scholar]
- Wetts R, Serbedzija GN, Fraser SE. Cell lineage analysis reveals multipotent precursors in the ciliary margin of the frog retina. Dev Biol. 1989 Nov;136(1):254–263. [Abstract] [Google Scholar]
- Wu BY, Fodor EJ, Edwards RH, Rutter WJ. Nerve growth factor induces the proto-oncogene c-jun in PC12 cells. J Biol Chem. 1989 May 25;264(15):9000–9003. [Abstract] [Google Scholar]
Associated Data
Articles from Molecular Biology of the Cell are provided here courtesy of American Society for Cell Biology
Full text links
Read article at publisher's site: https://doi.org/10.1091/mbc.3.3.323
Read article for free, from open access legal sources, via Unpaywall: https://europepmc.org/articles/pmc275533?pdf=render
Citations & impact
Impact metrics
Citations of article over time
Alternative metrics
Smart citations by scite.ai
Explore citation contexts and check if this article has been
supported or disputed.
https://scite.ai/reports/10.1091/mbc.3.3.323
Article citations
Molecular Characterization of the Llamas (Lama glama) Casein Cluster Genes Transcripts (CSN1S1, CSN2, CSN1S2, CSN3) and Regulatory Regions.
PLoS One, 10(4):e0124963, 29 Apr 2015
Cited by: 13 articles | PMID: 25923814 | PMCID: PMC4414411
The histone deacetylase inhibitor trichostatin A induces neurite outgrowth in PC12 cells via the epigenetically regulated expression of the nur77 gene.
Neurosci Res, 88:39-48, 13 Aug 2014
Cited by: 16 articles | PMID: 25128386
Dibutyryl-cAMP up-regulates nur77 expression via histone modification during neurite outgrowth in PC12 cells.
J Biochem, 148(1):93-101, 07 Apr 2010
Cited by: 20 articles | PMID: 20375114
Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway.
Proc Natl Acad Sci U S A, 102(34):12065-12070, 11 Aug 2005
Cited by: 84 articles | PMID: 16099831 | PMCID: PMC1189326
Regulation of Ras-MAPK pathway mitogenic activity by restricting nuclear entry of activated MAPK in endoderm differentiation of embryonic carcinoma and stem cells.
J Cell Biol, 164(5):689-699, 23 Feb 2004
Cited by: 41 articles | PMID: 14981092 | PMCID: PMC2172165
Go to all (21) article citations
Similar Articles
To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.
Hierarchical analysis of the nerve growth factor-dependent and nerve growth factor-independent differentiation signaling pathways in PC12 cells with protein kinase inhibitors.
J Neurosci Res, 42(2):207-219, 01 Oct 1995
Cited by: 9 articles | PMID: 8568921
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(4):2257-2261, 01 Feb 1990
Cited by: 33 articles | PMID: 2105318
Protein kinase C-epsilon plays a role in neurite outgrowth in response to epidermal growth factor and nerve growth factor in PC12 cells.
Cell Growth Differ, 10(3):183-191, 01 Mar 1999
Cited by: 60 articles | PMID: 10099832
Microinjection strategies for the study of mitogenic signaling in mammalian cells.
Front Biosci, 1:d19-29, 01 Mar 1996
Cited by: 6 articles | PMID: 9159206
Review
Funding
Funders who supported this work.
NEI NIH HHS (1)
Grant ID: EY08153
NIA NIH HHS (1)
Grant ID: AG09735