ArticleMolecular biology of the cell2011
Phosphorylation of STEF/Tiam2 by protein kinase A is critical for Rac1 activation and neurite outgrowth in dibutyryl cAMP-treated PC12D cells.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- RhoGEF Tiam2 Regulates Glutamatergic Synaptic Transmission in Hippocampal CA1 Pyramidal Neurons.eNeuro · 2024Article
- Loss-of-function variants in TIAM1 are associated with developmental delay, intellectual disability, and seizures.American journal of human genetics · 2022Article
- Protein Kinase A in cellular migration-Niche signaling of a ubiquitous kinase.Frontiers in molecular biosciences · 2022Review
- GPCRs thatSmall GTPases · 2022Review
- TRP Channels Regulation of Rho GTPases in Brain Context and Diseases.Frontiers in cell and developmental biology · 2020Review
- DDX3 Modulates Neurite Development via Translationally Activating an RNA Regulon Involved in Rac1 Activation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- 8-Oxoguanine accumulation in mitochondrial DNA causes mitochondrial dysfunction and impairs neuritogenesis in cultured adult mouse cortical neurons under oxidative conditions.Scientific reports · 2016Article
- Guanine nucleotide exchange factor αPIX leads to activation of the Rac 1 GTPase/glycogen phosphorylase pathway in interleukin (IL)-2-stimulated T cells.The Journal of biological chemistry · 2015Article
- Regulating Rac in the nervous system: molecular function and disease implication of Rac GEFs and GAPs.BioMed research international · 2015Review
- Genetically encoded fluorescent biosensors for live-cell visualization of protein phosphorylation.Chemistry & biology · 2014Review
- PKA modulation of Rac in neuronal cells.Frontiers in cellular neuroscience · 2014Article
- Gpr126 functions in Schwann cells to control differentiation and myelination via G-protein activation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Neuronal Rho GEFs in synaptic physiology and behavior.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2013Review
- GDNF and endothelin 3 regulate migration of enteric neural crest-derived cells via protein kinase A and Rac1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- 1-42 β-amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death.Translational psychiatry · 2013Article
- Article
- ROCK1 feedback regulation of the upstream small GTPase RhoA.Cellular signalling · 2012Article
- Optogenetic reporters: Fluorescent protein-based genetically encoded indicators of signaling and metabolism in the brain.Progress in brain research · 2012Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The second messenger cAMP plays a pivotal role in neurite/axon growth and guidance, but its downstream pathways leading to the regulation of Rho GTPases, centrally implicated in neuronal morphogenesis, remain elusive. We examined spatiotemporal changes in Rac1 and Cdc42 activity and phosphatidylinositol 3,4,5-triphosphate (PIP(3)) concentration in dibutyryl cAMP (dbcAMP)-treated PC12D cells using Förster resonance energy transfer-based biosensors. During a 30-min incubation with dbcAMP, Rac1 activity gradually increased throughout the cells and remained at its maximal level. There was no change in PIP(3) concentration. After a 5-h incubation with dbcAMP, Rac1 and Cdc42 were activated at the protruding tips of neurites without PIP(3) accumulation. dbcAMP-induced Rac1 activation was principally mediated by protein kinase A (PKA) and Sif- and Tiam1-like exchange factor (STEF)/Tiam2. STEF depletion drastically reduced dbcAMP-induced neurite outgrowth. PKA phosphorylates STEF at three residues (Thr-749, Ser-782, Ser-1562); Thr-749 phosphorylation was critical for dbcAMP-induced Rac1 activation and neurite extension. During dbcAMP-induced neurite outgrowth, PKA activation at the plasma membrane became localized to neurite tips; this localization may contribute to local Rac1 activation at the same neurite tips. Considering the critical role of Rac1 in neuronal morphogenesis, the PKA-STEF-Rac1 pathway may play a crucial role in cytoskeletal regulation during neurite/axon outgrowth and guidance, which depend on cAMP signals.
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