Rap1 mediates sustained MAP kinase activation induced by nerve growth factor

Randall D. York, Hong Yao, Tara Dillon, Cindy L. Ellig, Stephani P. Eckert, Edwin W. McCleskey, Philip Stork

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Abstract

Activation of mitogen-activated protein (MAP) kinase (also known as extracellular-signal-regulated kinase, or ERK) by growth factors can trigger either cell growth or differentiation. The intracellular signals that couple growth factors to MAP kinase may determine the different effects of growth factors: for example, transient activation of MAP kinase by epidermal growth factor stimulates proliferation of PC12 cells, whereas they differentiate in response to nerve growth factor, which acts partly by inducing a sustained activation of MAP kinase. Here we show that activation of MAP kinase by nerve growth factor involves two distinct pathways: the initial activation of MAP kinase requires the small G protein Ras, but its activation is sustained by the small G protein Rap1. Rap1 is activated by CRK adaptor proteins and the guanine-nucleotide-exchange factor C3G, and forms a stable complex with B- Raf, an activator of MAP kinase. Rap1 is required for at least two indices of neuronal differentiation by nerve growth factor: electrical excitability and the induction of neuron-specific genes. We propose that the activation of Rapl by C3G represents a common mechanism to induce sustained activation of the MAP kinase cascade in cells that express B-Raf.

Original languageEnglish (US)
Pages (from-to)622-626
Number of pages5
JournalNature
Volume392
Issue number6676
DOIs
StatePublished - Apr 9 1998

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Nerve Growth Factor
Mitogen-Activated Protein Kinases
Intercellular Signaling Peptides and Proteins
Monomeric GTP-Binding Proteins
Guanine Nucleotide-Releasing Factor 2
PC12 Cells
Extracellular Signal-Regulated MAP Kinases
Epidermal Growth Factor
Neurons
Growth
Genes

ASJC Scopus subject areas

  • General

Cite this

York, R. D., Yao, H., Dillon, T., Ellig, C. L., Eckert, S. P., McCleskey, E. W., & Stork, P. (1998). Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature, 392(6676), 622-626. https://doi.org/10.1038/33451

Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. / York, Randall D.; Yao, Hong; Dillon, Tara; Ellig, Cindy L.; Eckert, Stephani P.; McCleskey, Edwin W.; Stork, Philip.

In: Nature, Vol. 392, No. 6676, 09.04.1998, p. 622-626.

Research output: Contribution to journalArticle

York, RD, Yao, H, Dillon, T, Ellig, CL, Eckert, SP, McCleskey, EW & Stork, P 1998, 'Rap1 mediates sustained MAP kinase activation induced by nerve growth factor', Nature, vol. 392, no. 6676, pp. 622-626. https://doi.org/10.1038/33451
York RD, Yao H, Dillon T, Ellig CL, Eckert SP, McCleskey EW et al. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature. 1998 Apr 9;392(6676):622-626. https://doi.org/10.1038/33451
York, Randall D. ; Yao, Hong ; Dillon, Tara ; Ellig, Cindy L. ; Eckert, Stephani P. ; McCleskey, Edwin W. ; Stork, Philip. / Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. In: Nature. 1998 ; Vol. 392, No. 6676. pp. 622-626.
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