ArticleThe Journal of biological chemistry2007
Regulation of protein phosphatase inhibitor-1 by cyclin-dependent kinase 5.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Role of Dopamine in the Heart in Health and Disease.International journal of molecular sciences · 2023Review
- Synaptic roles of cyclin-dependent kinase 5 & its implications in epilepsy.The Indian journal of medical research · 2017Review
- Characterizing PKA-Mediated Phosphorylation of Plexin Using Purified Proteins.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Multi-phasic bi-directional chemotactic responses of the growth cone.Scientific reports · 2016Article
- Cyclin-Dependent kinase 5 targeting prevents β-Amyloid aggregation involving glycogen synthase kinase 3β and phosphatases.Journal of neuroscience research · 2015Article
- Differential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis.Oncotarget · 2015Article
- Cdk5/p35 functions as a crucial regulator of spatial learning and memory.Molecular brain · 2014Article
- Article
- Cyclin-dependent kinase 5, a node protein in diminished tauopathy: a systems biology approach.Frontiers in aging neuroscience · 2014Review
- Bi-directional regulation of CaMKIIα phosphorylation at Thr286 by NMDA receptors in cultured cortical neurons.Journal of neurochemistry · 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
- The role of Cdk5 in cognition and neuropsychiatric and neurological pathology.Brain research bulletin · 2011Review
- The large isoforms of A-kinase anchoring protein 18 mediate the phosphorylation of inhibitor-1 by protein kinase A and the inhibition of protein phosphatase 1 activity.Molecular pharmacology · 2011Article
- Localization of dopamine- and cAMP-regulated phosphoprotein-32 and inhibitor-1 in area 9 of Macaca mulatta prefrontal cortex.Neuroscience · 2010Article
- Crosstalk between Cdk5 and GSK3beta: Implications for Alzheimer's Disease.Frontiers in molecular neuroscience · 2009Article
- Negative regulation of cyclin-dependent kinase 5 targets by protein kinase C.European journal of pharmacology · 2008Article
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 5 countries.
Funding
Abstract
Inhibitor-1, the first identified endogenous inhibitor of protein phosphatase 1 (PP-1), was previously reported to be a substrate for cyclin-dependent kinase 5 (Cdk5) at Ser67. Further investigation has revealed the presence of an additional Cdk5 site identified by mass spectrometry and confirmed by site-directed mutagenesis as Ser6. Basal levels of phospho-Ser6 inhibitor-1, as detected by a phosphorylation state-specific antibody against the site, existed in specific regions of the brain and varied with age. In the striatum, basal in vivo phosphorylation and dephosphorylation of Ser6 were mediated by Cdk5, PP-2A, and PP-1, respectively. Additionally, calcineurin contributed to dephosphorylation under conditions of high Ca2+. In biochemical assays the function of Cdk5-dependent phosphorylation of inhibitor-1 at Ser6 and Ser67 was demonstrated to be an intramolecular impairment of the ability of inhibitor-1 to be dephosphorylated at Thr35; this effect was recapitulated in two systems in vivo. Dephosphorylation of inhibitor-1 at Thr35 is equivalent to inactivation of the protein, as inhibitor-1 only serves as an inhibitor of PP-1 when phosphorylated by cAMP-dependent kinase (PKA) at Thr35. Thus, inhibitor-1 serves as a critical junction between kinase- and phosphatase-signaling pathways, linking PP-1 to not only PKA and calcineurin but also Cdk5.
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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.