ArticleMolecular and cellular biology2009
Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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
35 citing papers in PubMed, 53 citations in OpenAlex.
- Raf kinase inhibitor protein combined with phosphorylated extracellular signal-regulated kinase offers valuable prognosis in gastrointestinal stromal tumor.World journal of gastroenterology · 2023Trial
- Clinical and prognostic significance of Raf kinase inhibitory protein expression in gastrointestinal stromal tumors.World journal of gastroenterology · 2018Trial
- Review
- Protein Kinase A Phosphorylates a Conformationally High-energy State of Raf Kinase Inhibitory Protein.Journal of molecular biology · 2025Article
- Two Cysteines in Raf Kinase Inhibitor Protein Make Differential Contributions to Structural Dynamics In Vitro.Molecules (Basel, Switzerland) · 2025Article
- Review
- Cefotetan-bound human RKIP involves in Ras/Raf1/MEK/ERK signaling pathway.Acta biochimica et biophysica Sinica · 2022Article
- Sphingosine kinases regulate ER contacts with late endocytic organelles and cholesterol trafficking.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Raf kinase inhibitory protein reduces bradykinin receptor desensitization.Journal of neurochemistry · 2022Article
- Raf Kinase Inhibitory Protein regulates the cAMP-dependent protein kinase signaling pathway through a positive feedback loop.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Florigen and its homologs of FT/CETS/PEBP/RKIP/YbhB family may be the enzymes of small molecule metabolism: review of the evidence.BMC plant biology · 2022Review
- Insights of RKIP-Derived Suppression of Prostate Cancer.Cancers · 2021Review
- Review
- Suramin Targets the Conserved Ligand-Binding Pocket of Human Raf1 Kinase Inhibitory Protein.Molecules (Basel, Switzerland) · 2021Article
- NF-κB sub-pathways and HIV cure: A revisit.EBioMedicine · 2021Review
- PEBP1 suppresses HIV transcription and induces latency by inactivating MAPK/NF-κB signaling.EMBO reports · 2020Article
- RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact.Cancers · 2018Review
- Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a loss or switch in the function of yeast or plant RKIP homologues. However, the mechanism by which the pocket influences RKIP function is unknown. Here we show that the pocket integrates two regulatory signals, phosphorylation and ligand binding, to control RKIP inhibition of Raf-1. RKIP association with Raf-1 is prevented by RKIP phosphorylation at S153. The P74L mutation increases kinase interaction and RKIP phosphorylation, enhancing Raf-1/MAPK signaling. Conversely, ligand binding to the RKIP pocket inhibits kinase interaction and RKIP phosphorylation by a noncompetitive mechanism. Additionally, ligand binding blocks RKIP association with Raf-1. Nuclear magnetic resonance studies reveal that the pocket is highly dynamic, rationalizing its capacity to interact with distinct partners and be involved in allosteric regulation. Our results show that RKIP uses a flexible pocket to integrate ligand binding- and phosphorylation-dependent interactions and to modulate the MAPK signaling pathway. This mechanism is an example of an emerging theme involving the regulation of signaling proteins and their interaction with effectors at the level of protein dynamics.
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What OpenQuestion holds
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.