ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent Extracellular Signal-regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated protein 1b distribution in neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
- The Role of Vitamin D in Parkinson's Disease: Evidence from Serum Concentrations, Supplementation, andNeuroSci · 2025Review
- A Retrospective Tribute to Dr. Harish Pant (1938-2023) and His Seminal Work on Cyclin Dependent Kinase 5.Neurochemical research · 2024Article
- Integrated proteomics and phosphoproteomics revealed druggable kinases in neoadjuvant chemotherapy resistant tongue cancer.Frontiers in cell and developmental biology · 2022Article
- Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells.Biomolecules · 2020Article
- CB1R regulates CDK5 signaling and epigenetically controls Rac1 expression contributing to neurobehavioral abnormalities in mice postnatally exposed to ethanol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Tale of the Good and the Bad Cdk5: Remodeling of the Actin Cytoskeleton in the Brain.Molecular neurobiology · 2018Review
- Synaptic roles of cyclin-dependent kinase 5 & its implications in epilepsy.The Indian journal of medical research · 2017Review
- p35 and Rac1 underlie the neuroprotection and cognitive improvement induced by CDK5 silencing.Journal of neurochemistry · 2015Article
- CDK5 contributes to neuronal apoptosis via promoting MEF2D phosphorylation in rat model of intracerebral hemorrhage.Journal of molecular neuroscience : MN · 2015Article
- Regulating Rac in the nervous system: molecular function and disease implication of Rac GEFs and GAPs.BioMed research international · 2015Review
- TFP5, a peptide derived from p35, a Cdk5 neuronal activator, rescues cortical neurons from glucose toxicity.Journal of Alzheimer's disease : JAD · 2014Article
- Maturation and integration of adult born hippocampal neurons: signal convergence onto small Rho GTPases.Frontiers in synaptic neuroscience · 2013Article
- Article
- Cdk5/p25-induced cytosolic PLA2-mediated lysophosphatidylcholine production regulates neuroinflammation and triggers neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- The Role of Pharmacokinetics and Pharmacodynamics in Early Drug Development with reference to the Cyclin-dependent Kinase (Cdk) Inhibitor - Roscovitine.Sultan Qaboos University medical journal · 2011Article
- Regulation of Neuronal Function by Ras-GRF Exchange Factors.Genes & cancer · 2011Article
- Nestin negatively regulates postsynaptic differentiation of the neuromuscular synapse.Nature neuroscience · 2011Article
- Cyclin-dependent kinase 5 regulates endothelial cell migration and angiogenesis.The Journal of biological chemistry · 2010Article
- Cdk5-mediated phosphorylation of delta-catenin regulates its localization and GluR2-mediated synaptic activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed kinase the activity of which is dependent on association with its neuron-specific activators, p35 and p39. Cdk5 activity is critical for the proper formation of cortical structures and lamination during development. In the adult nervous system, Cdk5 function is implicated in cellular adhesion, dopamine signaling, neurotransmitter release, and synaptic activity. In addition, Cdk5 is also involved in "cross-talk" with other signal transduction pathways. To further examine its involvement in cross-talk with other pathways, we identified proteins that interacted with p35 using the yeast two-hybrid system. We report here that p35 associates with Ras guanine nucleotide releasing factor 2 (RasGRF2) in coimmunoprecipitation and colocalization studies using transfected cell lines as well as primary cortical neurons. Additionally, Cdk5 phosphorylates RasGRF2 both in vitro and in vivo, leading to a decrease in Rac-guanidine exchange factor activity and a subsequent reduction in extracellular signal-regulated kinase 1/2 activity. We show that p35/Cdk5 phosphorylates RasGRF2 on serine737, which leads to an accumulation of RasGRF2 in the neuronal cell bodies coinciding with an accumulation of microtubule-associated protein 1b. The membrane association of p35 and subsequent localization of Cdk5 activity toward RasGRF2 and Rac provide insights into important cellular signaling processes that occur at the membrane, resulting in downstream effects on signal transduction cascades.
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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.