ArticleThe Journal of biological chemistry2016
Protein Kinase A-independent Ras Protein Activation Cooperates with Rap1 Protein to Mediate Activation of the Extracellular Signal-regulated Kinases (ERK) by cAMP.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Cocaine-Induced Immediate-Early Gene Expression in the Nucleus Accumbens: Roles of Separate cAMP Sensors.Journal of neurochemistry · 2026Article
- M2-like GAMs secreting CSTA drive glioblastoma progression via the ITGB4-TGFB1 feedback axis.Journal of translational medicine · 2026Article
- ucOCN Promotes Testosterone Synthesis via the PKA-MAPK/ERK-CREB Signaling Pathway in Porcine Leydig Cells.Cells · 2025Article
- PKA restricts ERK signaling in learning and memory Kenyon cell neurons.Cellular signalling · 2025Article
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids.Molecular cancer research : MCR · 2024Article
- Rosmarinic Acid Present inPlants (Basel, Switzerland) · 2024Article
- Signalling of Adrenoceptors: Canonical Pathways and New Paradigms.Handbook of experimental pharmacology · 2024Review
- Review
- Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer.NPJ breast cancer · 2022Article
- SGSM2 inhibits thyroid cancer progression by activating RAP1 and enhancing competitive RAS inhibition.Cell death & disease · 2022Article
- βLung · 2021Article
- Temporal pattern and synergy influence activity of ERK signaling pathways during L-LTP induction.eLife · 2021Article
- SUZ12 Loss Amplifies the Ras/ERK Pathway by Activating Adenylate Cyclase 1 in NF1-Associated Neurofibromas.Frontiers in oncology · 2021Article
- Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis.Pigment cell & melanoma research · 2021Review
- Signaling diversity enabled by Rap1-regulated plasma membrane ERK with distinct temporal dynamics.eLife · 2020Article
- The Mystery of Rap1 Suppression of Oncogenic Ras.Trends in cancer · 2020Review
- The road to ERK activation: Do neurons take alternate routes?Cellular signalling · 2020Review
- C3G contributes to platelet activation and aggregation by regulating major signaling pathways.Signal transduction and targeted therapy · 2020Article
- Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cyclic adenosine monophosphate (cAMP) is an important mediator of hormonal stimulation of cell growth and differentiation through its activation of the extracellular signal-regulated kinase (ERK) cascade. Two small G proteins, Ras and Rap1, have been proposed to mediate this activation, with either Ras or Rap1 acting in distinct cell types. Using Hek293 cells, we show that both Ras and Rap1 are required for cAMP signaling to ERKs. The roles of Ras and Rap1 were distinguished by their mechanism of activation, dependence on the cAMP-dependent protein kinase (PKA), and the magnitude and kinetics of their effects on ERKs. Ras was required for the early portion of ERK activation by cAMP and was activated independently of PKA. Ras activation required the Ras/Rap guanine nucleotide exchange factor (GEF) PDZ-GEF1. Importantly, this action of PDZ-GEF1 was disrupted by mutation within its putative cyclic nucleotide-binding domain within PDZ-GEF1. Compared with Ras, Rap1 activation of ERKs was of longer duration. Rap1 activation was dependent on PKA and required Src family kinases and the Rap1 exchanger C3G. This is the first report of a mechanism for the cooperative actions of Ras and Rap1 in cAMP activation of ERKs. One physiological role for the sustained activation of ERKs is the transcription and stabilization of a range of transcription factors, including c-FOS. We show that the induction of c-FOS by cAMP required both the early and sustained phases of ERK activation, requiring Ras and Rap1, as well as for each of the Raf isoforms, B-Raf and C-Raf.
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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.