ArticlePloS one2014
Distinct pathways of ERK1/2 activation by hydroxy-carboxylic acid receptor-1.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
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- Retraction: Distinct pathways of ERK1/2 activation by hydroxy-carboxylic acid receptor-1.PloS one · 2025Article
- Lactate/Hydroxycarboxylic Acid Receptor 1 in Alzheimer's Disease: Mechanisms and Therapeutic Implications-Exercise Perspective.Molecular neurobiology · 2024Review
- Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner.iScience · 2024Article
- Lactate administration induces skeletal muscle synthesis by influencing Akt/mTOR and MuRF1 in non-trained mice but not in trained mice.Physiological reports · 2024Article
- Activation of Lactate Receptor Positively Regulates Skeletal Muscle Mass in Mice.Physiological research · 2023Article
- Antipsychotics impair regulation of glucose metabolism by central glucose.Molecular psychiatry · 2022Article
- Beyond Mechanical Tension: A Review of Resistance Exercise-Induced Lactate Responses & Muscle Hypertrophy.Journal of functional morphology and kinesiology · 2022Review
- Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation.Metabolites · 2022Article
- Lactate drives cellular DNA repair capacity: Role of lactate and related short-chain fatty acids in cervical cancer chemoresistance and viral infection.Frontiers in cell and developmental biology · 2022Review
- Lactate Is Answerable for Brain Function and Treating Brain Diseases: Energy Substrates and Signal Molecule.Frontiers in nutrition · 2022Review
- Lactate Suppresses Retroviral Transduction in Cervical Epithelial Cells through DNA-PKcs Modulation.International journal of molecular sciences · 2021Article
- Lactate regulates autophagy through ROS-mediated activation of ERK1/2/m-TOR/p-70S6K pathway in skeletal muscle.Journal of cell communication and signaling · 2021Article
- Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review.Frontiers in cellular and infection microbiology · 2021Review
- Hydroxycarboxylic Acid Receptor 1 and Neuroprotection in a Mouse Model of Cerebral Ischemia-Reperfusion.Frontiers in physiology · 2021Article
- Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus.PloS one · 2020Article
- The Lactate Receptor HCAR1 Modulates Neuronal Network Activity through the Activation of GThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse.Physiological reports · 2018Article
- Glycolysis-Derived Compounds From Astrocytes That Modulate Synaptic Communication.Frontiers in neuroscience · 2018Review
Corrections and comments
- Retraction · 2025-03-04Concerns/Issues about Data · Concerns/Issues about Image · Duplication of Data · Duplication of/in Article · Duplication of/in Image · Euphemisms for Duplication · Unreliable Data · Unreliable Image · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanistic investigations have shown that, upon agonist activation, hydroxy-carboxylic acid receptor-1(HCA1) couples to a Gi protein and inhibits adenylate cyclase activity, leading to inhibition of liberation of free fatty acid. However, the underlying molecular mechanisms for HCA1 signaling remain largely unknown. Using CHO-K1 cells stably expressing HCA1, and L6 cells, which endogenously express rat HCA1 receptors, we found that activation of ERK1/2 by HCA1 was rapid, peaking at 5 min, and was significantly blocked by pertussis toxin. Furthermore, time course experiments with different kinase inhibitors demonstrated that HCA1 induced ERK1/2 activation via the extracellular Ca2+, PKC and IGF-I receptor transactivation-dependent pathways. In addition, we observed that pretreated the cells with M119K, an inhibitor of Gβγ subunit-dependent signaling, effectively attenuated the ERK1/2 activation triggered by HCA1, suggesting a critical role for βγ-subunits in HCA1-activated ERK1/2 phosphorylation. Furthermore, the present results also indicated that the arrestin2/3 were not required for ERK1/2 activation. In conclusion, our findings demonstrate that upon binding to agonist, HCA1 receptors initially activate Gi, leading to dissociation of the Gβγ subunit from activated Gi, and subsequently induce ERK1/2 activation via two distinct pathways: one PKC-dependent pathway and the other IGF-IR transactivation-dependent pathway. Our results provide the first in-depth evidence that defines the molecular mechanism of HCA1-mediated ERK1/2 activation.
Indexed as
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What Socratic 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 Socratic graph.