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A requirement for extracellular signal-regulated kinase (ERK) function in the activation of AP-1 by Ha-Ras, phorbol 12-myristate 13-acetate, and serum.
Open accessAbstract
The role of ERK-1 and ERK-2 in wild-type (wt) Ha-Ras, phorbol 12-myristate 13-acetate (PMA), and serum-induced AP-1 activity was studied. Microinjection of ERK-specific substrate peptides inhibited the induction of AP-1 activity by all three stimuli, whereas a control peptide had no effect. By using eukaryotic expression constructs encoding wt ERK-1 and kinase-deficient mutants of ERKs 1 and 2, it was found that ERK-1 and ERK-2 activities are required for AP-1 activation stimulated by either wt Ha-Ras, PMA, or serum. Overexpression of ERK-1 augmented wt Ha-Ras stimulation of AP-1, while having no effect upon PMA or serum stimulation. Overexpression of either kinase-deficient ERK-1 or kinase-deficient ERK-2 partially inhibited AP-1 activation by wt Ha-Ras but had no effect on PMA or serum-induced activation. Coexpression of both interfering mutants abolished AP-1 induction by wt Ha-Ras, PMA, or serum. We conclude that ERKs are necessary components in the pathway leading to the activation of AP-1 stimulated by these agents.
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Hibi, M., Lin, A., Smeal, T., Minden, A., & Karin, M. (1993) · Genes & Development · doi:10.1101/gad.7.11.2135 · Cited by 1,886
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Bar-Sagi, D., & Feramisco, J. R. (1986) · Science · doi:10.1126/science.3090687 · Cited by 734
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Metadata
- Authors
- Frost, J. A., Geppert, T. D., Cobb, M. H., & Feramisco, J. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1994-04-26
- Volume
- 91
- Issue
- 9
- Pages
- 3844-3848
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1964201687
- Cited by
- 218
- References
- 2
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: A requirement for extracellular signal-regulated kinase (ERK) function in the activation of AP-1 by Ha-Ras, phorbol 12-myristate 13-acetate, and serum. https://app.cochat.ai/papers/10.1073/pnas.91.9.3844
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- Frost, J. A., Geppert, T. D., Cobb, M. H., & Feramisco, J. R. (1994). A requirement for extracellular signal-regulated kinase (ERK) function in the activation of AP-1 by Ha-Ras, phorbol 12-myristate 13-acetate, and serum. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.91.9.3844
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