A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation

Megan J. Robinson, Stephen A. Stippec, Elizabeth Goldsmith, Michael A. White, Melanie H. Cobb

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266 Citations (Scopus)

Abstract

Background: Mitogen-activated protein (MAP) kinases are ubiquitous components of many signal transduction pathways. Constitutively active variants have been isolated for every component of the extracellular-signal-regulated kinase 1 (ERK1) and ERK2 MAP kinase pathway except for the ERK itself. Results: To create an activated ERK2 variant, we fused ERK2 to the low activity form of its upstream regulator, the MAP kinase kinase MEK1. The ERK2 in this fusion protein was active in the absence of extracellular signals. ExpressiOn of the fusion protein in mammalian cells did not activate endogenous ERK1 or ERK2. It was sufficient, however, to induce activation of the transcription factors Elk-1 and AP-1, neurite extension in PC12 cells in the absence of nerve growth factor, and foci of morphologically and growth-transformed NIH3T3 cells, if the fusion protein was localized to the nucleus. A cytoplasmic fusion protein was without effect. Conclusions: Activation of ERK2 is sufficient to cause several transcriptional and phenotypic responses in mammalian cells. Nuclear localization of activated ERK2 is required to induce these events.

Original languageEnglish (US)
Pages (from-to)1141-1150
Number of pages10
JournalCurrent Biology
Volume8
Issue number21
StatePublished - Oct 22 1998

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neurites
Mitogen-Activated Protein Kinases
mitogen-activated protein kinase
Fusion reactions
Mitogen-Activated Protein Kinase 3
ets-Domain Protein Elk-1
Proteins
Chemical activation
Cells
cells
Signal transduction
proteins
MAP Kinase Signaling System
Cell Fusion
PC12 Cells
Mitogen-Activated Protein Kinase Kinases
Transcription Factor AP-1
Nerve Growth Factor
Neurites
nerve growth factor

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation. / Robinson, Megan J.; Stippec, Stephen A.; Goldsmith, Elizabeth; White, Michael A.; Cobb, Melanie H.

In: Current Biology, Vol. 8, No. 21, 22.10.1998, p. 1141-1150.

Research output: Contribution to journalArticle

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AU - Cobb, Melanie H.

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