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Cyclic AMP-Mediated Inhibition of Cell Growth Requires the Small G Protein Rap1
Open accessAbstract
In many normal and transformed cell types, the intracellular second messenger cyclic AMP (cAMP) blocks the effects of growth factors and serum on mitogenesis, proliferation, and cell cycle progression. cAMP exerts these growth-inhibitory effects via inhibition of the mitogen-activated protein (MAP) kinase cascade. Here, using Hek293 and NIH 3T3 cells, we show that cAMP's inhibition of the MAP kinase cascade is mediated by the small G protein Rap1. Activation of Rap1 by cAMP induces the association of Rap1 with Raf-1 and limits Ras-dependent activation of ERK. In NIH 3T3 cells, Rap1 is required not only for cAMP's inhibition of ERK activation but for inhibition of cell proliferation and mitogenesis as well.
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Cites
A role for Rho in Ras transformation
Qiu, R. G., Chen, J., McCormick, F., & Symons, M. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.25.11781 · Cited by 533
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Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A
Lee, H., Rezai-Zadeh, N., & Seto, E. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.2.765-773.2004 · Cited by 153
Ye, X., & Carew, T. J. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.013 · Cited by 121
Smiljanić, K., Prodić, I., Trifunovic, S., Krstić Ristivojević, M., Aćimović, M., Stanković Jeremić, J., Lončar, B., & Tešević, V. (2023) · Antioxidants · doi:10.3390/antiox12111988 · Cited by 24
Metadata
- Authors
- Schmitt, J. M., & Stork, P. J. S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2001-06
- Volume
- 21
- Issue
- 11
- Pages
- 3671-3683
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W1991930853
- Cited by
- 160
- References
- 1
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- green
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- Schmitt, J. M., & Stork, P. J. S. (2001). Cyclic AMP-Mediated Inhibition of Cell Growth Requires the Small G Protein Rap1. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.21.11.3671-3683.2001
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
