ArticleThe Journal of biological chemistry2017
Phosphorylation of Rap1 by cAMP-dependent Protein Kinase (PKA) Creates a Binding Site for KSR to Sustain ERK Activation by cAMP.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 64 citations in OpenAlex.
- Rab1A Promotes Hepatic Steatosis by Suppressing Mitophagy via the Raf-1/ERK1/2/PINK1 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- M2-like GAMs secreting CSTA drive glioblastoma progression via the ITGB4-TGFB1 feedback axis.Journal of translational medicine · 2026Article
- Levistolide A Alleviates Myocardial Ischemia-Reperfusion Injury Partly by Improving Calcium Homeostasis via the ADORA2B/cAMP/PKA/PLB/SERCA2α Signaling Axis.Current issues in molecular biology · 2026Article
- PKA restricts ERK signaling in learning and memory Kenyon cell neurons.Cellular signalling · 2025Article
- The Critical Role of the Bile Acid Receptor TGR5 in Energy Homeostasis: Insights into Physiology and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Article
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Review
- Disruption of the pro-oncogenic c-RAF-PDE8A complex represents a differentiated approach to treating KRAS-c-RAF dependent PDAC.Scientific reports · 2024Article
- Protein Kinase A in neurological disorders.Journal of neurodevelopmental disorders · 2024Review
- Signalling of Adrenoceptors: Canonical Pathways and New Paradigms.Handbook of experimental pharmacology · 2024Review
- Revisiting the roles of cAMP signalling in the progression of prostate cancer.The Biochemical journal · 2023Article
- Analysis of RAS and drug induced homo- and heterodimerization of RAF and KSR1 proteins in living cells using split Nanoluc luciferase.Cell communication and signaling : CCS · 2023Article
- Chemobrain: An accelerated aging process linking adenosine AInternational review of neurobiology · 2023Review
- Phostensin enables lymphocyte integrin activation and population of peripheral lymphoid organs.The Journal of experimental medicine · 2022Article
- Review
- From Physiological Properties to Selective Vulnerability of Motor Units in Amyotrophic Lateral Sclerosis.Advances in neurobiology · 2022Article
- Temporal pattern and synergy influence activity of ERK signaling pathways during L-LTP induction.eLife · 2021Article
- Review
- The Rap1 small GTPase is a critical mediator of the effects of stress on prefrontal cortical dysfunction.Molecular psychiatry · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions 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. Using HEK293 cells as a model system, we have recently shown that both Ras and Rap1 are required for cAMP signaling to ERKs. However, cAMP-dependent Ras signaling to ERKs is transient and rapidly terminated by PKA phosphorylation of the Raf isoforms C-Raf and B-Raf. In contrast, cAMP-dependent Rap1 signaling to ERKs and Rap1 is potentiated by PKA. We show that this is due to sustained binding of B-Raf to Rap1. One of the targets of PKA is Rap1 itself, directly phosphorylating Rap1a on serine 180 and Rap1b on serine 179. We show that these phosphorylations create potential binding sites for the adaptor protein 14-3-3 that links Rap1 to the scaffold protein KSR. These results suggest that Rap1 activation of ERKs requires PKA phosphorylation and KSR binding. Because KSR and B-Raf exist as heterodimers within the cell, this binding also brings B-Raf to Rap1, allowing Rap1 to couple to ERKs through B-Raf binding to Rap1 independently of its Ras-binding domain.
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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.