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Inhibition by cAMP of Ras-Dependent Activation of Raf
Abstract
Activation of the Raf and extracellular signal-regulated kinases (ERKs) (or mitogen-activated protein kinases) are key events in mitogenic signaling, but little is known about interactions with other signaling pathways. Agents that raise levels of intracellular cyclic adenosine 3′,5′-monophosphate (cAMP) blocked DNA synthesis and signal transduction in Rat1 cells exposed to epidermal growth factor (EGF) or lysophosphatidic acid. In the case of EGF, receptor tyrosine kinase activity and association with the signaling molecules Grb2 and Shc were unaffected by cAMP. Likewise, EGF-dependent accumulation of the guanosine 5′-triphosphate-bound form of Ras was unaffected. In contrast, activation of Raf-1 and ERK kinases was inhibited. Thus, cAMP appears to inhibit signal transmission from Ras by preventing Ras-dependent activation of Raf-1.
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Cited by
Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers
Schaeffer, H. J., & Weber, M. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.2435 · Cited by 1,600
Mitogen-activated protein kinase cascades and regulation of gene expression
Su, B., & Karin, M. (1996) · Current Opinion in Immunology · doi:10.1016/s0952-7915(96)80131-2 · Cited by 747
Regulation of RAF protein kinases in ERK signalling
Lavoie, H., & Therrien, M. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3979 · Cited by 702
Martin, K. C., Michael, D., Rose, J. C., Barad, M., Casadio, A., Zhu, H., & Kandel, E. R. (1997) · Neuron · doi:10.1016/s0896-6273(00)80330-x · Cited by 545
A family of transcriptional adaptor proteins targeted by the E1A oncoprotein
Arany, Z., Newsome, D., Oldread, E., Livingston, D. M., & Eckner, R. (1995) · Nature · doi:10.1038/374081a0 · Cited by 533
Metadata
- Authors
- Cook, S. J., & McCormick, F.
- Venue
- Science
- Published
- 1993-11-12
- Volume
- 262
- Issue
- 5136
- Pages
- 1069-1072
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1993876642
- Cited by
- 922
- References
- 0
- FWCI
- 34.47
- Type
- journal article
- Language
- en
- Open access
- closed
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