Intact Ras function is required for sustained activation and nuclear translocation of extracellular signal-regulated kinases in nerve growth factor-stimulated PC12 cells

Gábor Boglári, Péter Erhardt, Geoffrey M. Cooper, J. Szeberényi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

PC12 pheochromocytoma cell lines expressing the dominant negative Ha-Ras Asn-17 protein at different levels were used in this study to analyze the relationship between nerve growth factor (NGF)-induced activation of members of the mitogen-activated protein kinase (MAPK) family, and neuritogenesis. In wild-type PC12 cells, NGF rapidly stimulated the extracellular signal-regulated kinases (ERKs). Kinase activation was sustained and was followed by the translocation of ERK 1 and ERK 2 into the nucleus ultimately leading to neurite outgrowth. In cells expressing relatively high levels of the inhibitory Ras protein, NGF stimulation of ERK 1 and ERK 2 as well as nuclear translocation of these protein kinases were greatly inhibited. In contrast, in PC12 subclones expressing low amounts of Ha-Ras Asn-17 the peak of ERK activation was only slightly reduced, but became transient in nature and was not followed by nuclear translocation of ERKs 1 and 2. Since all PC12 subclones expressing detectable levels of the dominant inhibitory Ras protein are resistant to NGF induction of neurite formation, our observations support the notion that sustained activation and translocation of ERKs into the nucleus are essential for NGF-induced neuronal differentiation of PC12 cells.

Original languageEnglish
Pages (from-to)54-58
Number of pages5
JournalEuropean Journal of Cell Biology
Volume75
Issue number1
Publication statusPublished - 1998

Fingerprint

PC12 Cells
Extracellular Signal-Regulated MAP Kinases
Nerve Growth Factor
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
ras Proteins
Neurites
Nuclear Proteins
Mitogen-Activated Protein Kinases
Protein Kinases
Phosphotransferases
Proteins

Keywords

  • Extracellular signalregulated kinases
  • Nerve growth factor
  • Neuronal differentiation
  • Nuclear translocation of ERKs
  • PC12 cells
  • Ras

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Intact Ras function is required for sustained activation and nuclear translocation of extracellular signal-regulated kinases in nerve growth factor-stimulated PC12 cells. / Boglári, Gábor; Erhardt, Péter; Cooper, Geoffrey M.; Szeberényi, J.

In: European Journal of Cell Biology, Vol. 75, No. 1, 1998, p. 54-58.

Research output: Contribution to journalArticle

@article{9d2a281da0464bd591cf82d43759b19a,
title = "Intact Ras function is required for sustained activation and nuclear translocation of extracellular signal-regulated kinases in nerve growth factor-stimulated PC12 cells",
abstract = "PC12 pheochromocytoma cell lines expressing the dominant negative Ha-Ras Asn-17 protein at different levels were used in this study to analyze the relationship between nerve growth factor (NGF)-induced activation of members of the mitogen-activated protein kinase (MAPK) family, and neuritogenesis. In wild-type PC12 cells, NGF rapidly stimulated the extracellular signal-regulated kinases (ERKs). Kinase activation was sustained and was followed by the translocation of ERK 1 and ERK 2 into the nucleus ultimately leading to neurite outgrowth. In cells expressing relatively high levels of the inhibitory Ras protein, NGF stimulation of ERK 1 and ERK 2 as well as nuclear translocation of these protein kinases were greatly inhibited. In contrast, in PC12 subclones expressing low amounts of Ha-Ras Asn-17 the peak of ERK activation was only slightly reduced, but became transient in nature and was not followed by nuclear translocation of ERKs 1 and 2. Since all PC12 subclones expressing detectable levels of the dominant inhibitory Ras protein are resistant to NGF induction of neurite formation, our observations support the notion that sustained activation and translocation of ERKs into the nucleus are essential for NGF-induced neuronal differentiation of PC12 cells.",
keywords = "Extracellular signalregulated kinases, Nerve growth factor, Neuronal differentiation, Nuclear translocation of ERKs, PC12 cells, Ras",
author = "G{\'a}bor Bogl{\'a}ri and P{\'e}ter Erhardt and Cooper, {Geoffrey M.} and J. Szeber{\'e}nyi",
year = "1998",
language = "English",
volume = "75",
pages = "54--58",
journal = "European Journal of Cell Biology (Supplement)",
issn = "0171-9335",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Intact Ras function is required for sustained activation and nuclear translocation of extracellular signal-regulated kinases in nerve growth factor-stimulated PC12 cells

AU - Boglári, Gábor

AU - Erhardt, Péter

AU - Cooper, Geoffrey M.

AU - Szeberényi, J.

PY - 1998

Y1 - 1998

N2 - PC12 pheochromocytoma cell lines expressing the dominant negative Ha-Ras Asn-17 protein at different levels were used in this study to analyze the relationship between nerve growth factor (NGF)-induced activation of members of the mitogen-activated protein kinase (MAPK) family, and neuritogenesis. In wild-type PC12 cells, NGF rapidly stimulated the extracellular signal-regulated kinases (ERKs). Kinase activation was sustained and was followed by the translocation of ERK 1 and ERK 2 into the nucleus ultimately leading to neurite outgrowth. In cells expressing relatively high levels of the inhibitory Ras protein, NGF stimulation of ERK 1 and ERK 2 as well as nuclear translocation of these protein kinases were greatly inhibited. In contrast, in PC12 subclones expressing low amounts of Ha-Ras Asn-17 the peak of ERK activation was only slightly reduced, but became transient in nature and was not followed by nuclear translocation of ERKs 1 and 2. Since all PC12 subclones expressing detectable levels of the dominant inhibitory Ras protein are resistant to NGF induction of neurite formation, our observations support the notion that sustained activation and translocation of ERKs into the nucleus are essential for NGF-induced neuronal differentiation of PC12 cells.

AB - PC12 pheochromocytoma cell lines expressing the dominant negative Ha-Ras Asn-17 protein at different levels were used in this study to analyze the relationship between nerve growth factor (NGF)-induced activation of members of the mitogen-activated protein kinase (MAPK) family, and neuritogenesis. In wild-type PC12 cells, NGF rapidly stimulated the extracellular signal-regulated kinases (ERKs). Kinase activation was sustained and was followed by the translocation of ERK 1 and ERK 2 into the nucleus ultimately leading to neurite outgrowth. In cells expressing relatively high levels of the inhibitory Ras protein, NGF stimulation of ERK 1 and ERK 2 as well as nuclear translocation of these protein kinases were greatly inhibited. In contrast, in PC12 subclones expressing low amounts of Ha-Ras Asn-17 the peak of ERK activation was only slightly reduced, but became transient in nature and was not followed by nuclear translocation of ERKs 1 and 2. Since all PC12 subclones expressing detectable levels of the dominant inhibitory Ras protein are resistant to NGF induction of neurite formation, our observations support the notion that sustained activation and translocation of ERKs into the nucleus are essential for NGF-induced neuronal differentiation of PC12 cells.

KW - Extracellular signalregulated kinases

KW - Nerve growth factor

KW - Neuronal differentiation

KW - Nuclear translocation of ERKs

KW - PC12 cells

KW - Ras

UR - http://www.scopus.com/inward/record.url?scp=2642624635&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2642624635&partnerID=8YFLogxK

M3 - Article

VL - 75

SP - 54

EP - 58

JO - European Journal of Cell Biology (Supplement)

JF - European Journal of Cell Biology (Supplement)

SN - 0171-9335

IS - 1

ER -