ArticlePloS one2014
Searching for novel Cdk5 substrates in brain by comparative phosphoproteomics of wild type and Cdk5-/- mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- The Recycling Endosomal (NaActa physiologica (Oxford, England) · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Quantitative phosphoproteomics reveals that nestin is a downstream target of dual leucine zipper kinase during retinoic acid-induced neuronal differentiation of Neuro-2a cells.BMC molecular and cell biology · 2025Article
- MAP2 phosphorylation: mechanisms, functional consequences, and emerging insights.Frontiers in cellular neuroscience · 2025Review
- Manipulating mitochondrial reactive oxygen species alters survival in unexpected ways in a Drosophila Cdk5 model of neurodegeneration.Biology open · 2024Article
- Protocols for Characterization of Cdk5 Kinase Activity.Current protocols · 2021Article
- Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons.Molecular & cellular proteomics : MCP · 2020Article
- Novel phospho-switch function of delta-catenin in dendrite development.The Journal of cell biology · 2020Article
- p39-associated Cdk5 activity regulates dendritic morphogenesis.Scientific reports · 2020Article
- ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle.PLoS biology · 2020Article
- Nestin Selectively Facilitates the Phosphorylation of the Lissencephaly-Linked Protein Doublecortin (DCX) by cdk5/p35 to Regulate Growth Cone Morphology and Sema3a Sensitivity in Developing Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Farnesyl Transferase Inhibitor Lonafarnib Enhances α7nAChR Expression Through Inhibiting DNA Methylation of CHRNA7 and Increases α7nAChR Membrane Trafficking.Frontiers in pharmacology · 2020Article
- Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception.Scientific reports · 2018Article
- Simvastatin Enhances Activity and Trafficking of α7 Nicotinic Acetylcholine Receptor in Hippocampal Neurons Through PKC and CaMKII Signaling Pathways.Frontiers in pharmacology · 2018Article
- Cdk5 Regulation of the GRAB-Mediated Rab8-Rab11 Cascade in Axon Outgrowth.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Article
- The Role of Cdk5 in Alzheimer's Disease.Molecular neurobiology · 2016Review
- Reduction of ciliary length through pharmacologic or genetic inhibition of CDK5 attenuates polycystic kidney disease in a model of nephronophthisis.Human molecular genetics · 2016Article
- Article
- Neuronal migration and protein kinases.Frontiers in neuroscience · 2014Review
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Protein phosphorylation is the most common post-translational modification that regulates several pivotal functions in cells. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase which is mostly active in the nervous system. It regulates several biological processes such as neuronal migration, cytoskeletal dynamics, axonal guidance and synaptic plasticity among others. In search for novel substrates of Cdk5 in the brain we performed quantitative phosphoproteomics analysis, isolating phosphoproteins from whole brain derived from E18.5 Cdk5+/+ and Cdk5-/- embryos, using an Immobilized Metal-Ion Affinity Chromatography (IMAC), which specifically binds to phosphorylated proteins. The isolated phosphoproteins were eluted and isotopically labeled for relative and absolute quantitation (iTRAQ) and mass spectrometry identification. We found 40 proteins that showed decreased phosphorylation at Cdk5-/- brains. In addition, out of these 40 hypophosphorylated proteins we characterized two proteins, :MARCKS (Myristoylated Alanine-Rich protein Kinase C substrate) and Grin1 (G protein regulated inducer of neurite outgrowth 1). MARCKS is known to be phosphorylated by Cdk5 in chick neural cells while Grin1 has not been reported to be phosphorylated by Cdk5. When these proteins were overexpressed in N2A neuroblastoma cell line along with p35, serine phosphorylation in their Cdk5 motifs was found to be increased. In contrast, treatments with roscovitine, the Cdk5 inhibitor, resulted in an opposite effect on serine phosphorylation in N2A cells and primary hippocampal neurons transfected with MARCKS. In summary, the results presented here identify Grin 1 as novel Cdk5 substrate and confirm previously identified MARCKS as a a bona fide Cdk5 substrate.
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