ArticleMolecular and cellular biology2011
Spatiotemporally regulated protein kinase A activity is a critical regulator of growth factor-stimulated extracellular signal-regulated kinase signaling in PC12 cells.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Role of the Glycine Transporter GlyT2 in the Neuronal Differentiation of PC12 Cells.International journal of molecular sciences · 2026Article
- Sensitive and Selective Next-Generation FRET-based PKA Biosensors.bioRxiv : the preprint server for biology · 2026Article
- Hepatocyte cholesterol content modulates glucagon receptor signalling.Molecular metabolism · 2022Article
- Review
- Myomegalin regulates Hedgehog pathway by controlling PDE4D at the centrosome.Molecular biology of the cell · 2021Article
- Biochemical Activity Architectures Visualized-Using Genetically Encoded Fluorescent Biosensors to Map the Spatial Boundaries of Signaling Compartments.Accounts of chemical research · 2021Review
- Amphetamines signal through intracellular TAAR1 receptors coupled to GαMolecular psychiatry · 2021Article
- The ERK mitogen-activated protein kinase signaling network: the final frontier in RAS signal transduction.Biochemical Society transactions · 2021Review
- An ultrasensitive biosensor for high-resolution kinase activity imaging in awake mice.Nature chemical biology · 2021Article
- Signalling, trafficking and glucoregulatory properties of glucagon-like peptide-1 receptor agonists exendin-4 and lixisenatide.British journal of pharmacology · 2020Article
- Signaling diversity enabled by Rap1-regulated plasma membrane ERK with distinct temporal dynamics.eLife · 2020Article
- Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.Chemical reviews · 2018Review
- Single-fluorophore biosensors for sensitive and multiplexed detection of signalling activities.Nature cell biology · 2018Article
- Local protein kinase A action proceeds through intact holoenzymes.Science (New York, N.Y.) · 2017Article
- Multiplexing PKA and ERK1&2 kinases FRET biosensors in living cells using single excitation wavelength dual colour FLIM.Scientific reports · 2017Article
- Bimodal antagonism of PKA signalling by ARHGAP36.Nature communications · 2016Article
- Confinement Sensing and Signal Optimization via Piezo1/PKA and Myosin II Pathways.Cell reports · 2016Article
- GGA3 mediates TrkA endocytic recycling to promote sustained Akt phosphorylation and cell survival.Molecular biology of the cell · 2015Article
- Frequency modulation of ERK activation dynamics rewires cell fate.Molecular systems biology · 2015Article
- Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome.The New England journal of medicine · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
PC12 cells exhibit precise temporal control of growth factor signaling in which stimulation with epidermal growth factor (EGF) leads to transient extracellular signal-regulated kinase (ERK) activity and cell proliferation, whereas nerve growth factor (NGF) stimulation leads to sustained ERK activity and differentiation. While cyclic AMP (cAMP)-mediated signaling has been shown to be important in conferring the sustained ERK activity achieved by NGF, little is known about the regulation of cAMP and cAMP-dependent protein kinase (PKA) in these cells. Using fluorescence resonance energy transfer (FRET)-based biosensors localized to discrete subcellular locations, we showed that both NGF and EGF potently activate PKA at the plasma membrane, although they generate temporally distinct activity patterns. We further show that both stimuli fail to induce cytosolic PKA activity and identify phosphodiesterase 3 (PDE3) as a critical regulator in maintaining this spatial compartmentalization. Importantly, inhibition of PDE3, and thus perturbation of the spatiotemporal regulation of PKA activity, dramatically increases the duration of EGF-stimulated nuclear ERK activity in a PKA-dependent manner. Together, these findings identify EGF and NGF as potent activators of PKA activity specifically at the plasma membrane and reveal a novel regulatory mechanism contributing to the growth factor signaling specificity achieved by NGF and EGF in PC12 cells.
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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.