ArticleScientific reports2015
Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827.Science advances · 2025Article
- CaMKK2: bridging the gap between Ca2+ signaling and energy-sensing.Essays in biochemistry · 2024Review
- Loss of calcium/calmodulin-dependent protein kinase kinase 2, transferrin, and transferrin receptor proteins in the temporal cortex of Alzheimer's patients postmortem is associated with abnormal iron homeostasis: implications for patient survival.Frontiers in cell and developmental biology · 2024Article
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- SGC-CAMKK2-1: A Chemical Probe for CAMKK2.Cells · 2023Article
- Molecular Mechanisms Underlying CaInternational journal of molecular sciences · 2022Review
- Computational analysis of cortical neuronal excitotoxicity in a large animal model of neonatal brain injury.Journal of neurodevelopmental disorders · 2022Article
- CAMKK2 regulates mitochondrial function by controlling succinate dehydrogenase expression, post-translational modification, megacomplex assembly, and activity in a cell-type-specific manner.Cell communication and signaling : CCS · 2021Article
- CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins.The Journal of biological chemistry · 2020Article
- In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds.Molecules (Basel, Switzerland) · 2020Article
- Effects of Single-Nucleotide Polymorphisms in Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2): A Comprehensive Study.Computational and mathematical methods in medicine · 2020Article
- Polymorphisms in CAMKK2 associate with susceptibility to sensory neuropathy in HIV patients treated without stavudine.Journal of neurovirology · 2019Article
- 1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors.Molecules (Basel, Switzerland) · 2018Article
- Pharmacological inhibition of CaMKK2 with the selective antagonist STO-609 regresses NAFLD.Scientific reports · 2017Article
- Genetics of HIV-associated sensory neuropathy and related pain in Africans.Journal of neurovirology · 2017Review
- Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.CNS neuroscience & therapeutics · 2017Article
- Impact of Genetic Variation on Human CaMKK2 Regulation by CaScientific reports · 2017Article
- The Ca(2+)/Calmodulin/CaMKK2 Axis: Nature's Metabolic CaMshaft.Trends in endocrinology and metabolism: TEM · 2016Review
- Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients.Journal of neurovirology · 2016Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations that reduce expression or give rise to a Thr85Ser (T85S) mutation of Ca(2+)-CaM-dependent protein kinase kinase-2 (CaMKK2) have been implicated in behavioural disorders such as anxiety, bipolar and schizophrenia in humans. Here we report that Thr85 is an autophosphorylation site that endows CaMKK2 with a molecular memory that enables sustained autonomous activation following an initial, transient Ca(2+) signal. Conversely, autophosphorylation of Ser85 in the T85S mutant fails to generate autonomous activity but instead causes a partial loss of CaMKK2 activity. The loss of autonomous activity in the mutant can be rescued by blocking glycogen synthase kinase-3 (GSK3) phosphorylation of CaMKK2 with the anti-mania drug lithium. Furthermore, CaMKK2 null mice representing a loss of function model the human behavioural phenotypes, displaying anxiety and manic-like behavioural disturbances. Our data provide a novel insight into CaMKK2 regulation and its perturbation by a mutation associated with behavioural disorders.
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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.