ArticleThe EMBO journal1993
cAMP antagonizes p21ras-directed activation of extracellular signal-regulated kinase 2 and phosphorylation of mSos nucleotide exchange factor.
Article in The EMBO journal, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
83 citing papers in PubMed, 362 citations in OpenAlex.
- Article
- The cAMP-signaling cancers: Clinically-divergent disorders with a common central pathway.Frontiers in endocrinology · 2022Review
- Review
- Feedback activation of neurofibromin terminates growth factor-induced Ras activation.Cell communication and signaling : CCS · 2016Article
- Prostacyclin regulates bone growth via the Epac/Rap1 pathway.Endocrinology · 2015Article
- Local cAMP signaling in disease at a glance.Journal of cell science · 2013Review
- Phosphodiesterase-8A binds to and regulates Raf-1 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling.Genomics & informatics · 2012Article
- The alternative Epac/cAMP pathway and the MAPK pathway mediate hCG induction of leptin in placental cells.PloS one · 2012Article
- Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases.Progress in retinal and eye research · 2009Review
- cAMP-mediated induction of cyclin E sensitizes growth-arrested adipose stem cells to DNA damage-induced apoptosis.Molecular biology of the cell · 2008Article
- Epac and PKA: a tale of two intracellular cAMP receptors.Acta biochimica et biophysica Sinica · 2008Review
- Dibutyryl cAMP stimulates the proliferation of SH-SY5Y human neuroblastoma cells by up-regulating Skp2 protein.Journal of cancer research and clinical oncology · 2007Article
- Cyclic AMP selectively uncouples mitogen-activated protein kinase cascades from activating signals.Molecular and cellular biology · 2006Article
- Epac activation converts cAMP from a proliferative into a differentiation signal in PC12 cells.Molecular biology of the cell · 2005Article
- Raf-1 serine 338 phosphorylation plays a key role in adhesion-dependent activation of extracellular signal-regulated kinase by epidermal growth factor.Molecular and cellular biology · 2005Article
- Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP.Oncogene · 2005Article
- DeltaRaf-1:ER* bypasses the cyclic AMP block of extracellular signal-regulated kinase 1 and 2 activation but not CDK2 activation or cell cycle reentry.Molecular and cellular biology · 2003Article
- Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms.Molecular and cellular biology · 2002Article
- Cyclic AMP-mediated inhibition of cell growth requires the small G protein Rap1.Molecular and cellular biology · 2001Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In fibroblasts, stimulation of receptor tyrosine kinases results in the activation of the extracellular signal-regulated kinase 2 (ERK2). The major signalling pathway employed by these receptors involves the activation of p21ras and raf-1 kinase. Here we show that in NIH3T3 and rat-1 fibroblasts, elevation of the intracellular cAMP level results in the inhibition of ERK2 activation induced by PDGF, EGF and insulin treatment. Analysis of various signalling intermediates shows that cAMP interferes at a site downstream of p21ras, but upstream of raf-1 kinase. Inhibition by cAMP depends on both the cAMP concentration and the absolute amount of p21ras molecules bound to GTP, suggesting a mechanism of competitive inhibition. Also TPA-induced, p21ras-independent, activation of raf-1 kinase and ERK2 is inhibited by cAMP. We have used the inhibitory effect of cAMP to investigate whether phosphorylation of mSos, a p21ras nucleotide exchange factor, is dependent on the activity of the raf-1 kinase/ERK2 pathway. We found that phosphorylation of mSos, as monitored by a mobility shift, is delayed with respect to p21ras and ERK2 activation and is inhibited by cAMP in a similar cell type- and concentration-dependent manner as the inactivation of ERK2. These results provide evidence for a model of p21ras-directed signalling towards ERK2 that feeds back on mSos by regulating its phosphorylation status and that can be negatively modulated by protein kinase A and positively modulated by protein kinase C action.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.