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PMID: 1627832 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Testing the in vivo role of protein kinase C and c-fos in neurite outgrowth by microinjection of antibodies into PC12 cells.

Molecular biology of the cell ·Vol. 3 ·No. 3 ·1992-03-00 ·Pages 323-33

Altin JG, Wetts R, Riabowol KT, Bradshaw RA

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.

Related Genes
c-fos
MeSH Terms
Animals Antibodies Antibodies, Monoclonal Cell Division/physiology Fibroblast Growth Factors/physiology Microinjections Nerve Growth Factors/physiology Neurites/enzymology,physiology PC12 Cells Protein Kinase C/immunology,physiology Proto-Oncogene Proteins c-fos/immunology,physiology Rats
Chemicals
Antibodies Antibodies, Monoclonal Nerve Growth Factors Proto-Oncogene Proteins c-fos Fibroblast Growth Factors Protein Kinase C
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Altin J G
Department of Biological Chemistry, College of Medicine, University of California, Irvine.
Wetts R
Riabowol K T
Bradshaw R A
References (58)
58 references, click to expand
  1. 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):327-34 PMID: 2730662
  2. v-src genes stimulate neurite outgrowth in pheochromocytoma (PC12) variants unresponsive to neurotrophic factors.
    J Neurosci Res. 1989 Sep;24(1):67-71 PMID: 2810397
  3. 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):3538-44 PMID: 2914963
  4. 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):1185-92 PMID: 3277634
  5. Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells.
    J Neurosci. 1987 Nov;7(11):3639-53 PMID: 3316527
  6. 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):2353-7 PMID: 3458200
  7. Cellular ras activity and tumor cell proliferation.
    Exp Cell Res. 1987 Jul;171(1):232-42 PMID: 3622632
  8. Multiple influences of a heparin-binding growth factor on neuronal development.
    J Cell Biol. 1987 Mar;104(3):635-43 PMID: 3818795
  9. Domain structure and phosphorylation of protein kinase C.
    J Biol Chem. 1987 Feb 15;262(5):2291-7 PMID: 3818597
  10. 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):2367-78 PMID: 3782300
  11. Activated N-ras gene induces neuronal differentiation of PC12 rat pheochromocytoma cells.
    J Cell Physiol. 1986 Oct;129(1):71-6 PMID: 3760034
  12. Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines.
    Science. 1985 Sep 20;229(4719):1265-8 PMID: 4035354
  13. 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):333-40 PMID: 2403640
  14. Antisense-fos RNA causes partial reversion of the transformed phenotypes induced by the c-Ha-ras oncogene.
    Mol Cell Biol. 1990 Apr;10(4):1545-55 PMID: 1690847
  15. Nerve growth factor regulates tyrosine hydroxylase gene transcription through a nucleoprotein complex that contains c-Fos.
    Genes Dev. 1990 Apr;4(4):477-91 PMID: 1972929
  16. The regulation and function of c-fos and other immediate early genes in the nervous system.
    Neuron. 1990 Apr;4(4):477-85 PMID: 1969743
  17. 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):453-62 PMID: 2161931
  18. 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):1333-9 PMID: 2157719
  19. Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB.
    Neuron. 1990 Apr;4(4):571-82 PMID: 2157471
  20. 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):1556-63 PMID: 2108319
  21. 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):2257-61 PMID: 2105318
  22. Production of 1,2-diacylglycerol in PC12 cells by nerve growth factor and basic fibroblast growth factor.
    J Neurochem. 1990 May;54(5):1666-76 PMID: 2324742
  23. The nerve growth factor: biochemistry, synthesis, and mechanism of action.
    Annu Rev Neurosci. 1980;3:353-402 PMID: 6106451
  24. Nerve growth factor-induced neuronal differentiation of PC12 pheochromocytoma cells: lack of inhibition by a tumor promoter.
    Brain Res. 1982 Sep 9;247(1):115-9 PMID: 7127107
  25. 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):6059-63 PMID: 310552
  26. Characterization and isolation of proteolytically modified nerve growth factor.
    Biochemistry. 1976 Dec 14;15(25):5543-52 PMID: 999827
  27. 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):145-55 PMID: 2049181
  28. Distinct protein targets for signals acting at the c-fos serum response element.
    Science. 1991 Jan 11;251(4990):189-92 PMID: 1898992
  29. Differential induction of primary-response (TIS) genes in PC12 pheochromocytoma cells and the unresponsive variant PC12nnr5.
    J Biol Chem. 1991 Mar 25;266(9):5401-6 PMID: 2005087
  30. 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):4460-6 PMID: 3162237
  31. 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):8646-52 PMID: 2785993
  32. ras-induced neuronal differentiation of PC12 cells: possible involvement of fos and jun.
    Mol Cell Biol. 1989 Aug;9(8):3174-83 PMID: 2507902
  33. Differentiation of PC12 cells with v-src: comparison with nerve growth factor.
    J Neurosci Res. 1989 Sep;24(1):49-58 PMID: 2810396
  34. 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):18452-8 PMID: 3142878
  35. Nerve growth factor regulates gene expression by several distinct mechanisms.
    Mol Cell Biol. 1989 Jan;9(1):135-43 PMID: 2538715
  36. Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene.
    Nature. 1987 Nov 19-25;330(6145):269-72 PMID: 3313065
  37. 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):4553-6 PMID: 3325827
  38. Induction of the proto-oncogene fos by nerve growth factor.
    Proc Natl Acad Sci U S A. 1985 Nov;82(21):7330-4 PMID: 2997786
  39. Differentiation of PC12 phaeochromocytoma cells induced by v-src oncogene.
    Nature. 1985 Aug 8-14;316(6028):557-9 PMID: 2993898
  40. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation.
    Cell. 1985 Oct;42(3):841-8 PMID: 2996779
  41. Nerve growth factor action is mediated by cyclic AMP- and Ca+2/phospholipid-dependent protein kinases.
    J Cell Biol. 1986 Sep;103(3):887-93 PMID: 2875079
  42. The catalytic subunit of cAMP-dependent protein kinase induces expression of genes containing cAMP-responsive enhancer elements.
    Nature. 1988 Nov 3;336(6194):83-6 PMID: 2847055
  43. Studies and perspectives of protein kinase C.
    Science. 1986 Jul 18;233(4761):305-12 PMID: 3014651
  44. Nerve growth factor rapidly induces c-fos mRNA in PC12 rat pheochromocytoma cells.
    Proc Natl Acad Sci U S A. 1986 Jul;83(13):4789-93 PMID: 3014510
  45. Inhibition of growth factor-induced differentiation of PC12 cells by microinjection of antibody to ras p21.
    Nature. 1986 Feb 20-26;319(6055):680-2 PMID: 3005866
  46. The effect of fibroblast growth factor on PC12 cells.
    J Neurosci. 1985 Feb;5(2):307-16 PMID: 2983039
  47. Calcium and growth factor pathways of c-fos transcriptional activation require distinct upstream regulatory sequences.
    Mol Cell Biol. 1988 Jul;8(7):2787-96 PMID: 3136322
  48. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes.
    Cell. 1988 Aug 12;54(4):541-52 PMID: 3135940
  49. Enhancement of inositol phospholipid metabolism and activation of protein kinase C in ras-transformed rat fibroblasts.
    J Biol Chem. 1988 Dec 5;263(34):17975-80 PMID: 3056934
  50. A general procedure for screening inhibitory antibodies: application for identifying anti-protein kinase C antibodies.
    Anal Biochem. 1988 Apr;170(1):31-7 PMID: 3291639
  51. Cell lineage analysis reveals multipotent precursors in the ciliary margin of the frog retina.
    Dev Biol. 1989 Nov;136(1):254-63 PMID: 2478403
  52. Microinjection of fos-specific antibodies blocks DNA synthesis in fibroblast cells.
    Mol Cell Biol. 1988 Apr;8(4):1670-6 PMID: 2454395
  53. Role of ion flux in the control of c-fos expression.
    Nature. 1986 Aug 7-13;322(6079):552-5 PMID: 2426600
  54. Nerve growth factor-induced differentiation in PC-12 cells is blocked by fos oncogene.
    Oncogene. 1989 Oct;4(10):1193-9 PMID: 2552373
  55. Nerve growth factor induces the proto-oncogene c-jun in PC12 cells.
    J Biol Chem. 1989 May 25;264(15):9000-3 PMID: 2542296
  56. Dynamic interactions of c-fos protein in serum-stimulated 3T3 cells.
    J Cell Physiol. 1989 Mar;138(3):493-502 PMID: 2494195
  57. Enucleation of the rat pheochromocytoma clonal cell line, PC12: effect on neurite outgrowth.
    J Cell Physiol. 1989 Nov;141(2):301-9 PMID: 2808539
  58. Induction of neurite outgrowth from chick embryonic ganglia explants by activators of protein kinase C.
    Neurosci Lett. 1989 May 8;99(3):257-62 PMID: 2725953
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.3.3.323
Published
1992-03-00
Pages
323-33
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC275533
Subset
IM
Grants
NIA NIH HHS · AG09735 · United States
NEI NIH HHS · EY08153 · United States
External Links
PubMed source DOI: 10.1091/mbc.3.3.323 PMC Full Text View journal details
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