ArticleMolecular and cellular biology1999
Protein kinase A-dependent and -independent signaling pathways contribute to cyclic AMP-stimulated proliferation.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 184 citations in OpenAlex.
- Comparative pathogenicity of vaccinia virus and mpox virus infections in CAST/EiJ mice: Exploring splenomegaly and transcriptomic profiles.Animal models and experimental medicine · 2025Article
- Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids.Molecular cancer research : MCR · 2024Article
- Unraveling the Complex Interplay Between Transcription Factors and Signaling Molecules in Thyroid Differentiation and Function, From Embryos to Adults.Frontiers in endocrinology · 2021Review
- Arecoline Enhances Phosphodiesterase 4A Activity to Promote Transforming Growth Factor-β-Induced Buccal Mucosal Fibroblast Activation via cAMP-Epac1 Signaling Pathway.Frontiers in pharmacology · 2021Article
- The Emerging Role of Insulin Receptor Isoforms in Thyroid Cancer: Clinical Implications and New Perspectives.International journal of molecular sciences · 2018Review
- cAMP attenuates TGF-β's profibrotic responses in osteoarthritic synoviocytes: involvement of hyaluronan and PRG4.American journal of physiology. Cell physiology · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Oncogene-induced senescence and its evasion in a mouse model of thyroid neoplasia.Molecular and cellular endocrinology · 2018Article
- The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines.Endocrine · 2016Article
- PKA-dependent phosphorylation of ribosomal protein S6 does not correlate with translation efficiency in striatonigral and striatopallidal medium-sized spiny neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Switch in signaling control of mTORC1 activity after oncoprotein expression in thyroid cancer cell lines.The Journal of clinical endocrinology and metabolism · 2014Article
- Estrogens and stem cells in thyroid cancer.Frontiers in endocrinology · 2014Review
- Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt.American journal of physiology. Endocrinology and metabolism · 2013Article
- Functional mapping of protein kinase A reveals its importance in adult Schistosoma mansoni motor activity.PLoS neglected tropical diseases · 2013Article
- The alternative Epac/cAMP pathway and the MAPK pathway mediate hCG induction of leptin in placental cells.PloS one · 2012Article
- A Signaling Network of Thyroid-Stimulating Hormone.Journal of proteomics & bioinformatics · 2011Article
- H2S protects hippocampal neurons from anoxia-reoxygenation through cAMP-mediated PI3K/Akt/p70S6K cell-survival signaling pathways.Journal of molecular neuroscience : MN · 2011Article
- PKA and Epac synergistically inhibit smooth muscle cell proliferation.Journal of molecular and cellular cardiology · 2011Article
- cAMP-dependent activation of mammalian target of rapamycin (mTOR) in thyroid cells. Implication in mitogenesis and activation of CDK4.Molecular endocrinology (Baltimore, Md.) · 2010Article
- Rap1 promotes multiple pancreatic islet cell functions and signals through mammalian target of rapamycin complex 1 to enhance proliferation.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The effects of cyclic AMP (cAMP) on cell proliferation are cell type specific. Although the growth-inhibitory effects of cAMP have been well studied, much less is known regarding how cAMP stimulates proliferation. We report that cAMP stimulates proliferation through both protein kinase A (PKA)-dependent and PKA-independent signaling pathways and that phosphatidylinositol 3-kinase (PI3K) is required for cAMP-stimulated mitogenesis. In cells where cAMP is a mitogen, cAMP-elevating agents stimulate membrane ruffling, Akt phosphorylation, and p70 ribosomal S6 protein kinase (p70s6k) activity. cAMP effects on ruffle formation and Akt were PKA independent but sensitive to wortmannin. In contrast, cAMP-stimulated p70s6k activity was repressed by PKA inhibitors but not by wortmannin or microinjection of the N-terminal SH2 domain of the p85 regulatory subunit of PI3K, indicating that p70s6k and Akt can be regulated independently. Microinjection of highly specific inhibitors of PI3K or Rac1, or treatment with the p70s6k inhibitor rapamycin, impaired cAMP-stimulated DNA synthesis, demonstrating that PKA-dependent and -independent pathways contribute to cAMP-mediated mitogenesis. Direct elevation of PI3K activity through microinjection of an antibody that stimulates PI3K activity or stable expression of membrane-localized p110 was sufficient to confer hormone-independent DNA synthesis when accompanied by elevations in p70s6k activity. These findings indicate that multiple pathways contribute to cAMP-stimulated mitogenesis, only some of which are PKA dependent. Furthermore, they demonstrate that the ability of cAMP to stimulate both p70s6k- and PI3K-dependent pathways is an important facet of cAMP-regulated cell cycle progression.
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Registered trials
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.