ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Decreased cyclin-dependent kinase 5 (cdk5) activity is accompanied by redistribution of cdk5 and cytoskeletal proteins and increased cytoskeletal protein phosphorylation in p35 null mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 118 citations in OpenAlex.
- Exploring New Structures of Kinase Inhibitors and Multitarget Strategies in Alzheimer's Disease Treatment.Protein and peptide letters · 2025Review
- Identification and characterization of transcribed enhancers during cerebellar development through enhancer RNA analysis.BMC genomics · 2023Article
- Alzheimer's Disease: Significant Benefit from the Yeast-Based Models.International journal of molecular sciences · 2023Review
- Cdk5-mediated JIP1 phosphorylation regulates axonal outgrowth through Notch1 inhibition.BMC biology · 2022Article
- RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation.Cell death and differentiation · 2021Article
- CDK5: Key Regulator of Apoptosis and Cell Survival.Biomedicines · 2019Review
- Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging.Disease models & mechanisms · 2018Article
- PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress.Nature communications · 2017Article
- FKBP51 inhibits GSK3β and augments the effects of distinct psychotropic medications.Molecular psychiatry · 2016Article
- Article
- Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Hippocampal glycogen synthase kinase 3β is critical for the antidepressant effect of cyclin-dependent kinase 5 inhibitor in rats.Journal of molecular neuroscience : MN · 2014Article
- Physiological and pathological phosphorylation of tau by Cdk5.Frontiers in molecular neuroscience · 2014Review
- Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice.Toxicology reports · 2014Article
- Neuroprotective effect of Buyang Huanwu Decoction on spinal ischemia-reperfusion injury in rats is linked with inhibition of cyclin-dependent kinase 5.BMC complementary and alternative medicine · 2013Article
- Both cyclin I and p35 are required for maximal survival benefit of cyclin-dependent kinase 5 in kidney podocytes.American journal of physiology. Renal physiology · 2012Article
- Special Issue on "Cdk5 and Brain Disorders": Prologue.Brain disorders & therapy · 2012Article
- Changes in cGMP levels affect the localization of EGL-4 in AWC in Caenorhabditis elegans.PloS one · 2012Article
- Decreasing Levels of the cdk5 Activators, p25 and p35, Reduces Excitotoxicity in Striatal Neurons.Journal of Huntington's disease · 2012Article
- Mice lacking phosphatase PP2A subunit PR61/B'delta (Ppp2r5d) develop spatially restricted tauopathy by deregulation of CDK5 and GSK3beta.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Cdk5/p35 has been implicated in cytoskeletal protein phosphorylation in normal brain and in many human neurodegenerative disorders. Yet, mouse models of cdk5/p35 hyperactivity have not yielded corresponding changes in cytoskeletal protein phosphorylation. To elucidate the relationship between p35, cdk5, and the neuronal cytoskeleton, we deleted the p35 gene in mice having a pure C57BL/6 background. We found that p35 deficiency leads to a 38% reduction of cdk5 activity in adult brain. In addition, loss of p35 causes an anterograde redistribution of cdk5 toward peripheral neuronal processes. The unusual presence of nonphosphorylated neurofilament (NF) in aberrant axon fascicles and the relocation of tau and MAP2B from cell bodies and proximal neuronal processes to more distal sites of the neuropil in p35-/- mouse brain implicate p35 in neuronal trafficking, particularly in dynein-driven retrograde transport. In many axons of normal brain, cdk5 fails to colocalize with phosphorylated cytoskeletal protein epitopes. This observation, together with an unexpected increase of NF, tau, and MAP2B phosphoepitopes accompanying the decreased cdk5 activity in p35-/- mice, supports the idea that cdk5 does not phosphorylate cytoskeletal proteins directly. Rather, in structures where cdk5 does colocalize with phosphorylated cytoskeletal protein epitopes, it may function as a negative regulator of other proline-directed kinases that directly phosphorylate the proteins. Evidence for increased glycogen synthase kinase 3beta (GSK3beta) activity in p35-/- mice suggests that GSK3beta may be one such kinase regulated by cdk5. Our studies illustrate that p35 regulates the subcellular distribution of cdk5 and cytoskeletal proteins in neurons and that cdk5 has a hierarchical role in regulating the phosphorylation and function of cytoskeletal proteins.
Indexed as
Identifiers
14627648PMC6740918W2135026720What OpenQuestion 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 OpenQuestion graph.