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PMID: 1545805 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Phosphorylation of translation initiation factor eIF-4E is induced in a ras-dependent manner during nerve growth factor-mediated PC12 cell differentiation.

Molecular and cellular biology ·Vol. 12 ·No. 3 ·1992-03-00 ·Pages 1239-47

Frederickson RM, Mushynski WE, Sonenberg N

Abstract

Translation initiation factor eIF-4E, which binds to the 5' cap structure of eukaryotic mRNAs, is believed to play an important role in the control of cell growth. Consistent with this, overexpression of eIF-4E in fibroblasts results in their malignant transformation. The activity of eIF-4E is thought to be regulated by phosphorylation on a single serine residue (Ser-53). Treatment of rat pheochromocytoma (PC12) cells with nerve growth factor (NGF) strongly curtails their growth and causes their differentiation into cells that resemble sympathetic neurons. The present study shows that eIF-4E is rapidly phosphorylated in PC12 cells upon NGF treatment, resulting in a significant increase in the steady-state levels of the phosphorylated protein. In contrast, epidermal growth factor, a factor which elicits a weak mitogenic response in PC12 cells, did not significantly enhance eIF-4E phosphorylation. We also show that although the mitogen and tumor promoter, phorbol 12-myristate-13-acetate, is able to induce phosphorylation of eIF-4E in PC12 cells, the NGF-mediated increase is primarily a protein kinase C-independent response. The NGF-induced enhancement of eIF-4E phosphorylation is abrogated in PC12 cells expressing a dominant inhibitory ras mutant (Ser-17 replaced by Asn), indicating that eIF-4E phosphorylation is dependent on a ras signalling pathway. As phosphorylation of eIF-4E effects translation initiation, these results suggest that NGF-mediated and ras-dependent eIF-4E phosphorylation may play a role in switching the pattern of gene expression during the differentiation of PC12 cells.

Related Genes
ras
MeSH Terms
Animals Cell Differentiation Eukaryotic Initiation Factor-4E Genes, ras Isoelectric Focusing Kinetics Nerve Growth Factors/metabolism PC12 Cells Peptide Initiation Factors/metabolism Phosphorylation Precipitin Tests Protein Kinase C/metabolism Signal Transduction Tetradecanoylphorbol Acetate/pharmacology
Chemicals
Eukaryotic Initiation Factor-4E Nerve Growth Factors Peptide Initiation Factors Protein Kinase C Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Frederickson R M
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Mushynski W E
Sonenberg N
References (61)
61 references, click to expand
  1. Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties.
    Proc Natl Acad Sci U S A. 1989 May;86(9):3099-103 PMID: 2470089
  2. 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
  3. Differentiation of PC12 phaeochromocytoma cells induced by v-src oncogene.
    Nature. 1985 Aug 8-14;316(6028):557-9 PMID: 2993898
  4. Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation.
    Prog Nucleic Acid Res Mol Biol. 1988;35:173-207 PMID: 3065823
  5. Nerve growth factor, a differentiating agent, and epidermal growth factor, a mitogen, increase the activities of different S6 kinases in PC12 cells.
    J Biol Chem. 1988 Nov 5;263(31):15853-6 PMID: 3141398
  6. Cap recognition and the entry of mRNA into the protein synthesis initiation cycle.
    Trends Biochem Sci. 1988 Feb;13(2):52-6 PMID: 3238751
  7. Revertants of v-fos-transformed fibroblasts have mutations in cellular genes essential for transformation by other oncogenes.
    Cell. 1987 Nov 6;51(3):357-69 PMID: 3664639
  8. Nerve growth factor enhances the synthesis, phosphorylation, and metabolic stability of neurofilament proteins in PC12 cells.
    J Biol Chem. 1987 Jan 15;262(2):605-10 PMID: 3804999
  9. Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells.
    Nature. 1985 Jan 17-23;313(5999):241-3 PMID: 3918269
  10. Regulation of protein synthesis in mammalian cells. II. Inhibition of protein synthesis at the level of initiation during mitosis.
    J Mol Biol. 1970 Jun 28;50(3):655-70 PMID: 5529301
  11. The nerve growth factor: biochemistry, synthesis, and mechanism of action.
    Annu Rev Neurosci. 1980;3:353-402 PMID: 6106451
  12. Nerve growth factor-induced alteration in the response of PC12 pheochromocytoma cells to epidermal growth factor.
    J Cell Biol. 1981 Jan;88(1):189-98 PMID: 6259177
  13. Phosphorylation of ribosomal protein S6 in avian sarcoma virus-transformed chicken embryo fibroblasts.
    Proc Natl Acad Sci U S A. 1981 Jul;78(7):4112-5 PMID: 6270659
  14. Mechanism of inhibition of polypeptide chain initiation in heat-shocked Ehrlich ascites tumour cells.
    Eur J Biochem. 1984 Apr 2;140(1):209-14 PMID: 6705795
  15. New initiation factor activity required for globin mRNA translation.
    J Biol Chem. 1983 May 10;258(9):5804-10 PMID: 6853548
  16. Modulation of protein synthesis by nerve growth factor.
    J Biol Chem. 1979 Aug 25;254(16):7978-85 PMID: 224040
  17. Continuous protein synthesis is required to maintain the probability of entry into S phase.
    Cell. 1977 Sep;12(1):311-7 PMID: 902318
  18. Regulation of fibroblast cell cycle by serum.
    Nature. 1976 Mar 18;260(5548):248-50 PMID: 942592
  19. Transfer of proteins to membranes facilitates both cyanogen bromide cleavage and two-dimensional proteolytic mapping.
    Oncogene. 1990 Jun;5(6):921-3 PMID: 1688326
  20. Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases.
    Nature. 1991 Sep 12;353(6340):170-3 PMID: 1716348
  21. The trk proto-oncogene encodes a receptor for nerve growth factor.
    Cell. 1991 Apr 5;65(1):189-97 PMID: 1849459
  22. Epidermal growth factor or okadaic acid stimulates phosphorylation of eukaryotic initiation factor 4F.
    J Biol Chem. 1991 Feb 15;266(5):3162-6 PMID: 1993687
  23. Phosphorylation of eukaryotic translation initiation factor 4E is increased in Src-transformed cell lines.
    Mol Cell Biol. 1991 May;11(5):2896-900 PMID: 2017184
  24. Alteration of the major phosphorylation site of eukaryotic protein synthesis initiation factor 4E prevents its association with the 48 S initiation complex.
    J Biol Chem. 1990 Feb 15;265(5):2979-83 PMID: 2105935
  25. Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells.
    Mol Cell Biol. 1990 Oct;10(10):5314-23 PMID: 2118993
  26. Overexpression of eukaryotic protein synthesis initiation factor 4E in HeLa cells results in aberrant growth and morphology.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8212-6 PMID: 2122455
  27. Differential stimulation of phosphorylation of initiation factors eIF-4F, eIF-4B, eIF-3, and ribosomal protein S6 by insulin and phorbol esters.
    J Biol Chem. 1990 Jun 25;265(18):10611-6 PMID: 2191953
  28. Simultaneous cytoplasmic redistribution of ribosomal protein L32 mRNA and phosphorylation of eukaryotic initiation factor 4E after mitogenic stimulation of Swiss 3T3 cells.
    J Biol Chem. 1990 Mar 5;265(7):3619-22 PMID: 2303467
  29. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap.
    Nature. 1990 Jun 7;345(6275):544-7 PMID: 2348862
  30. Protein phosphorylation controls translation rates.
    J Biol Chem. 1989 Dec 15;264(35):20823-6 PMID: 2687263
  31. Tumor necrosis factor induces phosphorylation of a 28-kDa mRNA cap-binding protein in human cervical carcinoma cells.
    Proc Natl Acad Sci U S A. 1989 Nov;86(21):8417-21 PMID: 2813400
  32. A polypeptide in eukaryotic initiation factors that crosslinks specifically to the 5'-terminal cap in mRNA.
    Proc Natl Acad Sci U S A. 1978 Oct;75(10):4843-7 PMID: 217002
  33. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.
    Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424-8 PMID: 1065897
  34. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF.
    Nature. 1991 Mar 14;350(6314):158-60 PMID: 1706478
  35. Translational control in mammalian cells.
    Annu Rev Biochem. 1991;60:717-55 PMID: 1883206
  36. Phosphorylation of eIF-4F by protein kinase C or multipotential S6 kinase stimulates protein synthesis at initiation.
    J Biol Chem. 1991 Mar 15;266(8):4669-72 PMID: 2002015
  37. Platelet-derived growth factor stimulates phosphorylation of the 25 kDa mRNA cap binding protein (eIF-4E) in human lung fibroblasts.
    FEBS Lett. 1991 Jun 3;283(2):219-22 PMID: 2044759
  38. Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells.
    Mol Cell Biol. 1990 Oct;10(10):5324-32 PMID: 2118994
  39. 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
  40. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F.
    Mol Cell Biol. 1990 Mar;10(3):1134-44 PMID: 2304461
  41. 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
  42. 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
  43. Requirement for c-ras proteins during viral oncogene transformation.
    Nature. 1986 Apr 10-16;320(6062):540-3 PMID: 2938016
  44. 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
  45. Involvement of the 24-kDa cap-binding protein in regulation of protein synthesis in mitosis.
    J Biol Chem. 1987 Aug 15;262(23):11134-9 PMID: 3038908
  46. Phosphorylation site of eukaryotic initiation factor 4E.
    J Biol Chem. 1987 Aug 5;262(22):10434-7 PMID: 3112145
  47. Alterations of the lymphocyte-specific protein tyrosine kinase (p56lck) during T-cell activation.
    Mol Cell Biol. 1988 Oct;8(10):4353-61 PMID: 3141789
  48. Down regulation of protein kinase C in neuronal cells: effects on neurotransmitter release.
    J Neurosci. 1987 Apr;7(4):1198-206 PMID: 3471877
  49. Immunological evidence for two physiological forms of protein kinase C.
    Mol Cell Biol. 1987 Jan;7(1):85-96 PMID: 3561403
  50. Regulated phosphorylation and low abundance of HeLa cell initiation factor eIF-4F suggest a role in translational control. Heat shock effects on eIF-4F.
    J Biol Chem. 1987 Jan 5;262(1):380-8 PMID: 3793730
  51. Nerve growth factor and epidermal growth factor induce rapid transient changes in proto-oncogene transcription in PC12 cells.
    J Biol Chem. 1985 Nov 15;260(26):14101-10 PMID: 3877054
  52. Immunological detection of the messenger RNA cap-binding protein.
    J Biol Chem. 1985 Jul 5;260(13):7843-9 PMID: 3891747
  53. Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line.
    Nature. 1985 Nov 7-13;318(6041):73-5 PMID: 4058592
  54. Control of macromolecular synthesis in proliferating and resting Syrian hamster cells in monolayer culture. I. Ribosome function.
    J Cell Physiol. 1971 Feb;77(1):31-42 PMID: 5546177
  55. The regulation of initiation of mammalian protein synthesis.
    Prog Nucleic Acid Res Mol Biol. 1981;25:127-85 PMID: 6164076
  56. Nerve growth factor mediates phosphorylation of specific proteins.
    Cell. 1980 Nov;22(2 Pt 2):571-81 PMID: 6256087
  57. Two forms of purified m7G-cap binding protein with different effects on capped mRNA translation in extracts of uninfected and poliovirus-infected HeLa cells.
    J Biol Chem. 1981 Aug 10;256(15):7691-4 PMID: 6267020
  58. Heat shock-induced translational alterations in HeLa cells. Initiation factor modifications and the inhibition of translation.
    J Biol Chem. 1984 Oct 10;259(19):11882-9 PMID: 6384217
  59. Involvement of eukaryotic initiation factor 4A in the cap recognition process.
    J Biol Chem. 1983 Sep 25;258(18):11398-403 PMID: 6604056
  60. The effect of serum, EGF, PGF2 alpha and insulin on S6 phosphorylation and the initiation of protein and DNA synthesis.
    Cell. 1982 Aug;30(1):235-42 PMID: 6751557
  61. 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
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.3.1239-1247.1992
Published
1992-03-00
Pages
1239-47
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC369556
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.12.3.1239-1247.1992 PMC Full Text View journal details
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