Affinage

Showing CAMK2B — CAMK2 is a alias.

CAMK2B

Calcium/calmodulin-dependent protein kinase type II subunit beta · UniProt Q13554

Length
666 aa
Mass
72.7 kDa
Annotated
2026-06-09
80 papers in source corpus 31 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CaMKIIβ is a Ca2+/calmodulin-activated serine/threonine kinase that doubles as a structural actin-organizing protein, coupling calcium signaling to cytoskeletal dynamics in neurons (PMID:9768845, PMID:16928958). Its distinguishing feature is an alternatively spliced variable domain (requiring exon v1/E1) that confers direct F-actin binding and bundling not shared by CaMKIIα; CaMKIIβ thereby targets CaMKIIα/β heterooligomers to dendritic spines and the cell cortex, and isoforms lacking this exon fail to associate with F-actin (PMID:9768845, PMID:16928958, PMID:25031715). CaMKIIβ binds preferentially to stable F-actin and maintains polymerized actin in vivo, an association released by Ca2+/calmodulin binding, autophosphorylation, or PKC-mediated phosphorylation, creating a regulated structural-to-signaling switch that governs spine formation, elongation, and maintenance (PMID:18840684, PMID:28607044, PMID:30528771, PMID:35079728). Through this actin-binding/bundling activity CaMKIIβ controls radial migration of cortical neurons in balance with cofilin, and tightly regulated Thr287 autophosphorylation—both gains and losses—impairs neuronal migration and underlies a neurodevelopmental disorder caused by de novo CAMK2B mutations (PMID:29100089, PMID:29712998). As a kinase, CaMKIIβ phosphorylates defined substrates to remodel the cytoskeleton and synapse: LIMK1 at Thr508 to drive BDNF-induced neuritogenesis (PMID:23600483), Cdc20 at Ser51 at the PCM1-targeted centrosome to inhibit Cdc20-APC and trigger dendrite retraction (PMID:21725312), and spastin at Ser233/Ser562 to stabilize it against proteasomal degradation and promote neurite outgrowth (PMID:40645772). It also acts non-catalytically and through partner recruitment—serving as the calmodulin-free receptor for Arc in inverse synaptic tagging (PMID:22579289), scaffolding with drebrin in the spine core as a resting-state arrangement released by NMDA receptor activation (PMID:29675826, PMID:37659612), and acting upstream of ERK1/2 to drive GABAB receptor lysosomal degradation (PMID:37686242). CaMKIIβ activity is required for LTP, fear learning, locomotion, and sleep regulation (PMID:30528771, PMID:31064859, PMID:36194579, PMID:36543542), and beyond the nervous system it regulates autophagic flux via MLKL phosphorylation (PMID:34282994), adipocyte insulin signaling (PMID:34303021), and oligodendrocyte maturation and viability through actin stabilization and GSK3β antagonism (PMID:23785157, PMID:30674062). Structurally, the CaMKIIβ hub domain assembles into coexisting 14-mer and 16-mer oligomers that are less stable than those of CaMKIIα (PMID:38501502).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1998 High

    Established that CaMKIIβ, unlike CaMKIIα, binds F-actin and acts as a targeting module that docks CaMKII heterooligomers to dendritic spines, defining a non-catalytic localization function distinct from kinase activity.

    Evidence GFP-tagged CaMKII isoform live imaging and co-expression heterooligomer analysis in neurons

    PMID:9768845

    Open questions at the time
    • Did not define the structural determinant within CaMKIIβ responsible for F-actin binding
    • Did not establish how the interaction is regulated
  2. 2006 High

    Identified the alternatively spliced exon v1 as the determinant of F-actin association and showed CaMKIIβ bundles and phosphorylates actin, linking the splice-defined domain to both structural and enzymatic actions on the cytoskeleton.

    Evidence Splice deletion constructs, in vitro F-actin bundling, in-cell co-localization, and in vitro kinase assay on actin

    PMID:16928958

    Open questions at the time
    • Functional consequence of actin phosphorylation in vivo not resolved
    • Did not address regulation by Ca2+/CaM in cells
  3. 2008 High

    Showed CaMKIIβ selectively binds stable F-actin and maintains polymerized actin, and that Ca2+/calmodulin or high phosphorylation (not kinase inactivity) releases it, defining the regulated structural-to-signaling switch.

    Evidence FRAP of GFP-CaMKIIβ in CaMKIIα-free cortical neurons with pharmacological actin manipulation and deletion mutants

    PMID:18840684

    Open questions at the time
    • Specific phosphosites controlling release not mapped here
    • Downstream effects of actin stabilization on synaptic function not addressed
  4. 2011 High

    Defined a CaMKIIα-independent centrosomal function: CaMKIIβ phosphorylates Cdc20 at Ser51 to inhibit Cdc20-APC and drive dendrite retraction, extending CaMKIIβ substrate biology beyond actin.

    Evidence Neuronal knockdown in vitro and in vivo, PCM1 targeting identification, in vitro kinase assay mapping Cdc20 Ser51, and Cdc20-APC activity assay

    PMID:21725312

    Open questions at the time
    • How CaMKIIβ activity at the centrosome is triggered remains unclear
    • Relationship between centrosomal and spine pools not defined
  5. 2012 High

    Established CaMKIIβ as the calmodulin-free targeting receptor for Arc, mechanistically linking synaptic inactivity to AMPA receptor endocytosis in inverse synaptic tagging.

    Evidence Co-immunoprecipitation, CaMKIIβ knockout in vitro and in vivo, surface GluA1 immunofluorescence, and synaptic activity manipulation

    PMID:22579289

    Open questions at the time
    • Structural basis of the calmodulin-state-dependent Arc binding not resolved
    • Whether kinase activity is involved not addressed
  6. 2013 High

    Identified LIMK1 Thr508 as a CaMKIIβ substrate driving BDNF-induced neuritogenesis and showed CaMKIIβ (not α) is required, connecting CaMKIIβ to the cofilin/actin reorganization pathway.

    Evidence CaMKIIβ knockdown in cortical neurons, in vitro kinase assay, and kinase-dead LIMK1 rescue

    PMID:23600483

    Open questions at the time
    • In vivo requirement for LIMK1 phosphorylation by CaMKIIβ not tested
    • Single-lab finding
  7. 2013 High

    Demonstrated CaMKIIβ is required for oligodendrocyte maturation and myelin thickness, and that this function may be largely non-catalytic, broadening its role beyond neurons and beyond kinase activity.

    Evidence Oligodendrocyte cultures, Camk2b knockout mice, and Camk2b(A303R) kinase-dead knock-in mice with myelin thickness measurement

    PMID:23785157

    Open questions at the time
    • The structural mechanism mediating myelin thickness not defined
    • Partner proteins in oligodendrocytes not identified here
  8. 2016 High

    Distinguished developmental from acute requirements: Ca2+/calmodulin activation (not autonomous activity) is needed for locomotion, and deficits arise developmentally and are not localized to one brain region.

    Evidence Conditional Camk2b knockout, Camk2b(T287A) autonomy-block knock-in, and temporal/regional Cre deletion with behavioral assays

    PMID:27244486

    Open questions at the time
    • Specific developmental circuit affected not pinpointed
    • Molecular substrates underlying locomotion not identified
  9. 2017 High

    Established that tightly regulated Thr287 autophosphorylation is essential for neuronal migration and brain development, linking de novo CAMK2B mutations to a neurodevelopmental disorder.

    Evidence Whole-exome sequencing, autophosphorylation assays, and neuronal migration assays in vitro and in vivo

    PMID:29100089

    Open questions at the time
    • Downstream migration substrates of CaMKIIβ not defined here
    • Genotype-phenotype correlations across patients not fully resolved
  10. 2018 High

    Showed CaMKIIβ controls cortical radial migration through actin binding/bundling in balance with cofilin, and that F-actin-binding-domain autophosphorylation is required for fear learning, tying its structural switch directly to behavior.

    Evidence In utero electroporation with domain mutants; F-actin binding domain phosphoblock knock-in mice with fear conditioning

    PMID:29712998 PMID:30528771

    Open questions at the time
    • How migration and learning phenotypes mechanistically connect not defined
    • Precise kinetics of the actin-binding switch in vivo unresolved
  11. 2018 High

    Identified drebrin as a CaMKIIβ partner organizing a resting-state pool in the spine core that is released by NMDA receptor activation, defining how CaMKIIβ is positioned for activity-dependent redistribution.

    Evidence Yeast two-hybrid, FRAP in hippocampal neurons, drebrin knockdown, and NMDA receptor activation (later refined by STORM imaging)

    PMID:29675826 PMID:37659612

    Open questions at the time
    • Functional output of drebrin-dependent versus -independent pools not fully separated
    • Whether drebrin binding requires kinase activity not addressed
  12. 2019 High

    Demonstrated both Ca2+-dependent and autonomous CaMKII activity are essential for survival and LTP without altering PSD composition, separating CaMKII signaling from structural scaffolding of the postsynaptic density.

    Evidence Germline and adult-inducible Camk2a/Camk2b double knockouts, activity mutant mice, LTP electrophysiology, and PSD fractionation

    PMID:31064859

    Open questions at the time
    • Isoform-specific contributions of CaMKIIβ within the double KO not isolated
    • Substrates mediating survival not identified here
  13. 2019 Medium

    Showed CaMKIIβ antagonizes GSK3β to determine oligodendrocyte viability in an HIV-1 Tat model, adding a viability-control axis to CaMKIIβ oligodendrocyte biology.

    Evidence KN-93 inhibition and CaMKIIβ knockdown in oligodendrocyte cultures, GSK3β activity and viability assays, and Tat transgenic mice

    PMID:30674062

    Open questions at the time
    • Whether CaMKIIβ directly phosphorylates GSK3β not established
    • Single-lab finding
  14. 2021 High

    Extended CaMKIIβ (and CaMKII broadly) into non-neuronal physiology: regulating autophagic flux via MLKL phosphorylation, adipocyte insulin signaling, and stress resilience via TARPγ-8/AMPAR.

    Evidence Genetic/pharmacological MLKL studies with autophagy flux assays; adipocyte-specific CAMK2 knockout with metabolic phenotyping; in vivo ventral hippocampus manipulation with phosphorylation and behavioral readouts

    PMID:34113835 PMID:34282994 PMID:34303021

    Open questions at the time
    • Isoform-specific contribution of CaMKIIβ in autophagy and adipocyte roles not fully separated from other CaMKII isoforms
    • MLKL and TARPγ-8 phosphosite mapping for CaMKIIβ not detailed here
  15. 2022 High

    Showed distinct CaMKIIβ autophosphorylation states differentially control sleep induction versus maintenance, and that primate-specific splice isoforms with altered kinetics affect LTP, linking phospho-state and splicing to higher functions.

    Evidence Phosphomimetic/phosphoblock mutants with EEG sleep analysis; CRISPR knock-in of human branch point into mouse with LTP electrophysiology

    PMID:36194579 PMID:36543542

    Open questions at the time
    • Circuit-level basis of sleep-state control not resolved
    • Substrate-specificity changes of primate isoforms not fully mapped
  16. 2022 Medium

    Linked CaMKIIβ to spine calcium homeostasis, showing knockdown reduces store-operated calcium entry and causes mushroom spine loss.

    Evidence siRNA knockdown in hippocampal neurons with calcium imaging, spine morphology, and KN-62 inhibition

    PMID:35079728

    Open questions at the time
    • Mechanism connecting CaMKIIβ to nSOCE channels not defined
    • Single-lab finding
  17. 2023 High

    Defined an indirect signaling route: CaMKIIβ activates ERK1/2, which phosphorylates GABAB1 to trigger lysosomal receptor degradation, showing CaMKIIβ acts upstream rather than directly on the receptor.

    Evidence Site-directed mutagenesis of GABAB1 phosphosites, ERK1/2 inhibition, and CaMKIIβ manipulation with degradation assays under physiological and ischemic conditions

    PMID:37686242

    Open questions at the time
    • The direct CaMKIIβ substrate linking it to ERK1/2 activation not identified
    • Physiological context of GABAB downregulation incompletely defined
  18. 2024 High

    Resolved the CaMKIIβ hub architecture, showing coexisting 14-mer and 16-mer assemblies that are less stable than CaMKIIα hubs, providing a structural basis for isoform-specific oligomer behavior.

    Evidence X-ray crystallography (3.1 Å 14-mer, 3.4 Å 16-mer), mass photometry, temperature denaturation, and rational dimer mutagenesis

    PMID:38501502

    Open questions at the time
    • Functional consequence of variable oligomer size in cells not established
    • Relationship of hub stability to actin targeting not addressed
  19. 2024 High

    Implicated CaMKIIβ in neuromuscular junction stability, showing CaMKIIβ overexpression normalizes endplate fragmentation and corrects HDAC4-regulated synaptic gene programs in Myotonic Dystrophy type I models.

    Evidence HSALR and Mbnl1ΔE3/ΔE3 DM1 mouse models with AAV CaMKIIβ overexpression, endplate morphology, gene expression, and AChR turnover assays

    PMID:38769542

    Open questions at the time
    • Direct CaMKIIβ substrates at the NMJ not identified
    • Whether kinase activity mediates the rescue not separated
  20. 2025 High

    Identified spastin as a CaMKIIβ substrate (Ser233/Ser562) stabilized against degradation, mechanistically connecting CaMKIIβ to microtubule severing and neurite outgrowth.

    Evidence Co-IP, in vitro kinase assay mapping phosphosites, ubiquitination and degradation assays, neurite outgrowth, mEPSC recording, and behavioral tests

    PMID:40645772

    Open questions at the time
    • In vivo requirement for spastin phosphorylation by CaMKIIβ across tissues not established
    • How phosphorylation reduces ubiquitination mechanistically not detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct molecular axes of CaMKIIβ — actin structural targeting, defined substrate phosphorylation (Cdc20, LIMK1, spastin, MLKL), and scaffold/receptor functions (Arc, drebrin) — are coordinated through its splice variants, phospho-state, and hub oligomerization within a single cell remains unresolved, and the bulk of its in vivo substrate landscape is still being defined.
  • Most CaMKII substrates identified by phosphoproteomics in double-KO tissue lack direct validation [#30]
  • No unified model relating hub stability/oligomer size to functional output
  • Isoform-specific versus shared functions across CaMKIIα/β incompletely separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0060089 molecular transducer activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 3 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 1
Partners
ARCCAMK2ACDC20DBN1GSK3BLIMK1PCM1SPAST
Complex memberships
CaMKII holoenzyme (CaMKIIα/β heterooligomer)

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 CaMKIIβ (but not CaMKIIα) binds to F-actin in dendritic spines and cell cortex, functioning as a targeting module that localizes CaMKIIα/β heterooligomers to synaptic and cytoskeletal sites. When co-expressed, CaMKIIα and CaMKIIβ form large heterooligomers, and a small fraction of CaMKIIβ is sufficient to dock the predominant CaMKIIα to the actin cytoskeleton. GFP-tagged CaMKII isoform live imaging in neurons; co-expression heterooligomer analysis Neuron High 9768845
2006 CaMKIIβ association with the F-actin cytoskeleton requires inclusion of alternatively spliced exon v1; the neonatal variant CaMKIIβe (lacking exon v1) fails to associate with F-actin. CaMKIIβ (but not CaMKIIα) bundles F-actin filaments in vitro and can phosphorylate actin in vitro even by basal (unstimulated) activity in the absence of Ca2+/CaM. Alternative splicing analysis with deletion constructs; F-actin bundling in vitro assay; in-cell F-actin co-localization; in vitro kinase assay on actin Molecular biology of the cell High 16928958
2008 CaMKIIβ binds preferentially to stable (vs. dynamic) F-actin in embryonic cortical neurons. CaMKIIβ binding to F-actin is disrupted by Ca2+/calmodulin binding or by high phosphorylation, but not by kinase inactivity. CaMKIIβ over-expression increased F-actin-rich structures, while disruption of its F-actin binding reduced them, indicating CaMKIIβ binding to stable F-actin maintains polymerized F-actin in vivo. FRAP of GFP-CaMKIIβ in CaMKIIα-free embryonic cortical neurons; pharmacological F-actin stabilization/destabilization; deletion mutant analysis Proceedings of the National Academy of Sciences of the United States of America High 18840684
2011 CaMKIIβ operates at the centrosome (localized there by the targeting protein PCM1) in a CaMKIIα-independent manner to drive dendrite retraction and pruning. CaMKIIβ phosphorylates the E3 ubiquitin ligase substrate Cdc20 at Ser51, inducing Cdc20 dispersion from the centrosome, inhibiting centrosomal Cdc20-APC activity, and triggering the transition from dendrite growth to retraction. Knockdown in primary rat neurons and in vivo in rat cerebellar cortex; identification of PCM1 as centrosomal targeting partner; in vitro kinase assay identifying Cdc20 Ser51 as CaMKIIβ phosphorylation site; Cdc20-APC activity assay Nature neuroscience High 21725312
2012 Arc/Arg3.1 interacts with high affinity with CaMKIIβ that is not bound to calmodulin. Arc accumulates at inactive synapses via this interaction, leading to AMPA-R (GluA1) endocytosis. Loss of CaMKIIβ in vitro or in vivo abolished Arc upregulation at silenced synapses, establishing CaMKIIβ as the targeting receptor for Arc in 'inverse synaptic tagging'. Co-immunoprecipitation; in vivo CaMKIIβ knockout; immunofluorescence for surface GluA1; synaptic activity manipulations Cell High 22579289
2013 CaMKIIβ is critical for the morphological maturation of differentiating oligodendrocytes and regulates myelin thickness in vivo. CaMKIIβ has an actin-cytoskeleton-stabilizing role in oligodendrocytes, and its in vivo function in myelin thickness may be mediated by non-kinase-catalytic (structural) activity, as shown using Camk2b knockout and Camk2b(A303R) kinase-dead mutant mice. In vitro oligodendrocyte culture with CaMKIIβ manipulation; Camk2b knockout mice; Camk2b(A303R) kinase-dead knock-in mice; myelin thickness measurement The Journal of neuroscience High 23785157
2013 CaMKIIβ (but not CaMKIIα) is required for BDNF-induced neuritogenesis. CaMKIIβ phosphorylates LIM-kinase 1 (LIMK1) at Thr-508 in the kinase domain, activating LIMK1's cofilin-phosphorylating activity, which in turn drives actin cytoskeletal reorganization and primary neurite formation. CaMKIIβ knockdown in cortical neurons; in vitro kinase assay identifying LIMK1 Thr-508 phosphorylation; kinase-dead LIMK1 mutant rescue; pharmacological CaMK inhibition Genes to cells High 23600483
2015 CaMKIIβ promotes spine formation and elongation in cerebellar Purkinje cells through its F-actin bundling activity. Activation of group I mGluR (but not AMPAR) triggers PKC-mediated phosphorylation of CaMKIIβ, causing dissociation of the CaMKIIβ/F-actin complex. Defective PKC-mediated CaMKIIβ phosphorylation promotes excess F-actin bundling and leads to abnormally numerous and elongated spines. Purkinje cell spine morphology analysis; pharmacological mGluR activation; PKC inhibition; CaMKIIβ phosphorylation assay; IP3R1-deficient mouse model Proceedings of the National Academy of Sciences of the United States of America High 28607044
2016 Normal locomotion requires Ca2+/calmodulin-mediated activation of CAMK2B, but CAMK2B autonomous (Ca2+-independent) activity is largely dispensable. Severe locomotion deficits in Camk2b−/− mice are largely of developmental origin, as adult-onset deletion causes only mild deficits. These deficits cannot be attributed to a single brain area (cerebellum, striatum, or forebrain). Conditional Camk2b knockout (Camk2b(f/f)); Camk2b(T287A) knock-in (autonomous activity block); temporal and region-specific Cre-mediated deletion; behavioral locomotion assays Scientific reports High 27244486
2017 De novo mutations in CAMK2B that alter auto-phosphorylation at Thr287 (either decreasing or increasing it) also impair neuronal migration in vitro and in vivo, establishing that tightly regulated CAMK2B auto-phosphorylation is required for normal neuronal migration and brain development. Whole-exome sequencing; CAMK2 auto-phosphorylation assays in cell lines; neuronal migration assays in vitro and in vivo American journal of human genetics High 29100089
2018 CaMKIIβ controls radial migration of cortical projection neurons through its actin-binding and -bundling activities; knockdown accelerates migration while overexpression inhibits it. A fine-tuned balance between CaMKIIβ and cofilin activities is necessary for proper neuronal migration, placing CaMKIIβ upstream of actin dynamics in cortical neuron locomotion. In utero electroporation with CaMKIIβ knockdown/overexpression and actin-binding domain mutants; analysis of multipolar-bipolar transition and locomotion in cortical plate Molecular psychiatry High 29712998
2018 Autophosphorylation at the F-actin binding domain of CaMKIIβ is required for fear learning. Phosphoblock mutations in the actin-binding domain (knock-in mice) impair contextual and cued fear conditioning, demonstrating that proper regulation of CaMKIIβ–F-actin interaction is important for learning and memory. CaMKIIβ F-actin binding domain phosphoblock knock-in mice; contextual and cued fear conditioning behavioral tests Neurobiology of learning and memory High 30528771
2018 CaMKIIβ is localized in dendritic spines as both drebrin-dependent and drebrin-independent pools. Drebrin knockdown causes diffuse localization of CaMKIIβ and increases the stable CaMKIIβ fraction. NMDA receptor activation releases CaMKIIβ from the drebrin-binding F-actin complex, shifting CaMKIIβ association to the PSD. Yeast two-hybrid identification of drebrin–CaMKIIβ interaction; FRAP analysis in rat hippocampal neurons; drebrin knockdown; NMDA receptor activation Journal of neurochemistry High 29675826
2019 Both Ca2+-dependent and Ca2+-independent (autonomous) activity of CAMK2 are essential for survival. Combined loss of CAMK2A and CAMK2B abolishes LTP but does not affect synaptic transmission or the biochemical composition of the postsynaptic density, demonstrating that CAMK2 signaling is required for postnatal development and mature brain function beyond PSD structural organization. Germline and adult-inducible Camk2a/Camk2b double knockout mice; Ca2+-dependent/autonomous activity mutant mice; LTP electrophysiology; PSD biochemical fractionation; brain morphology The Journal of neuroscience High 31064859
2019 CaMKIIβ interacts with GSK3β and opposes its activity in oligodendrocytes. HIV-1 Tat increases CaMKIIβ activity in oligodendrocytes; pharmacological or genetic inhibition of CaMKIIβ increases GSK3β activity and promotes death in mature oligodendrocytes treated with Tat, showing that CaMKIIβ–GSK3β interaction determines oligodendrocyte viability. CaMKII inhibitor (KN-93) treatment; CaMKIIβ knockdown in oligodendrocyte cultures; GSK3β activity assay; cell viability assays; in vivo Tat transgenic mice Journal of neurochemistry Medium 30674062
2021 CAMK2 activation disrupts adipocyte insulin signaling and lowers insulin receptor levels, contributes to lipolysis and TNFα-induced inflammation. Adipocyte-specific CAMK2 deletion in obese mice improved glucose intolerance and insulin resistance, establishing CAMK2 as a regulator of adipocyte metabolic function. Conditional adipocyte-specific CAMK2 knockout mice; in vitro differentiated adipocytes; insulin signaling analysis; glucose and insulin tolerance tests Molecular metabolism High 34303021
2021 CAMK2/CaMKII (including the β isoform) phosphorylates MLKL in a RIPK3-independent manner during short-term nutrient starvation, facilitating autophagic flux by promoting autophagosome maturation and fusion with lysosomes, independent of necroptosis. Genetic knockdown/knockout of CAMK2 and MLKL in multiple cell lines; pharmacological inhibition; LC3-II and p62 flux assays; pHluorin-mKate2-LC3 autolysosome incorporation assay Autophagy High 34282994
2021 CaMKIIβ-mediated phosphorylation of TARPγ-8 enhances GluA1 AMPA receptor expression at postsynaptic sites in the ventral hippocampus, enabling stress resilience; this CaMKIIβ/TARPγ-8/AMPAR pathway mediates gene-environment interactions controlling behavioral susceptibility and resilience to chronic stress. CaMKIIβ activity manipulation in vivo in ventral hippocampus; phosphorylation assays; GluA1 surface expression measurement; behavioral stress paradigms in GxE mouse models iScience Medium 34113835
2022 Distinct phosphorylation states of CaMKIIβ differentially control sleep induction versus sleep maintenance: a mutant mimicking constitutive-active auto-phosphorylation promotes wakefulness-to-sleep transition, while mutants mimicking subsequent multisite auto-phosphorylation suppress sleep-to-wakefulness transition. Sleep regulation depends on CaMKIIβ kinase activity. Camk2b knockout mice; CaMKIIβ activation/inhibition in mice; phosphomimetic and phosphoblock CaMKIIβ mutants; EEG sleep duration/state analysis PLoS biology High 36194579
2022 Primate-specific CAMK2B alternative splice isoforms (generated through evolutionarily weakened branch point sequences) show altered kinetic properties and changed substrate specificity. Introducing a weaker human branch point sequence into mouse Camk2b via CRISPR/Cas9 strongly alters splicing in brain and severely impairs LTP at CA3-CA1 synapses. Identification of primate-specific CAMK2B isoforms; in vitro kinase assays of splice isoforms; CRISPR/Cas9 knock-in of human branch point into mouse; LTP electrophysiology in hippocampal slices Life science alliance High 36543542
2022 CaMKIIβ knockdown reduces store-operated calcium entry (nSOCE) amplitude in dendritic spines of hippocampal neurons and causes mushroom spine loss, linking CaMKIIβ to regulation of spine calcium homeostasis and structural maintenance. CaMKIIβ knockdown by siRNA in primary hippocampal neurons; calcium imaging for nSOCE; spine morphology analysis; pharmacological CaMKII inhibition (KN-62) IBRO neuroscience reports Medium 35079728
2022 Super-resolution STORM imaging shows CaMKIIβ co-localizes with drebrin in the core region of dendritic spines; NMDA receptor activation dissociates CaMKIIβ from drebrin in the core region. Drebrin knockdown decreases CaMKIIβ in the core but not the submembrane region, establishing drebrin-dependent clustering of CaMKIIβ in the spine core as a resting-state standby arrangement. STORM super-resolution microscopy; NMDA receptor activation; drebrin knockdown in hippocampal neurons Neuroscience research Medium 37659612
2023 CaMKIIβ activates ERK1/2, which then phosphorylates GABAB1 at S867 and T872, triggering lysosomal degradation of GABAB receptors. Mutational inactivation of T872 or blocking ERK1/2 prevents receptor degradation, revealing that CaMKIIβ does not directly phosphorylate S867 but instead acts upstream of ERK1/2 in the GABAB receptor degradation pathway. Site-directed mutagenesis of GABAB1 phosphosites; ERK1/2 inhibition; CaMKIIβ manipulation; receptor degradation assays in cultured neurons under physiological and ischemic conditions International journal of molecular sciences High 37686242
2024 CaMKIIβ hub domains adopt both 14-mer and 16-mer oligomeric assemblies that coexist in solution. CaMKIIβ hub is less stable than CaMKIIα hub, with larger oligomers being more stable. A dimeric CaMKIIβ hub unit created by rational mutagenesis is significantly less stable than the oligomer, and both hubs populate an intermediate during unfolding. X-ray crystallography (3.1 Å 14-mer and 3.4 Å 16-mer crystal structures); mass photometry; temperature denaturation; rational mutagenesis to create dimer Protein science High 38501502
2024 CaMKIIβ deregulation contributes to neuromuscular junction destabilization in Myotonic Dystrophy type I. CaMKIIβ/βM overexpression normalizes endplate fragmentation and corrects aberrant synaptic gene expression (including abnormal HDAC4 accumulation) in innervated Mbnl1ΔE3/ΔE3 muscle, placing CaMKIIβ upstream of HDAC4-regulated synaptic gene programs. HSALR and Mbnl1ΔE3/ΔE3 DM1 mouse models; AAV-mediated CaMKIIβ overexpression; endplate morphology; synaptic gene expression; HDAC4 immunostaining; AChR turnover assays Skeletal muscle High 38769542
2025 CaMKIIβ interacts with and phosphorylates spastin at Ser233 and Ser562, reducing its polyubiquitination and suppressing proteasomal degradation, thereby increasing spastin protein stability, enhancing its microtubule-severing activity, and promoting neurite outgrowth in hippocampal neurons. Co-IP identifying CaMKIIβ–spastin interaction; in vitro kinase assay mapping Ser233/Ser562 phosphosites; ubiquitination assays; proteasomal degradation assays; neurite outgrowth analysis; mEPSC electrophysiology; behavioral tests (Y-maze, Morris water maze) The Journal of neuroscience High 40645772
2018 Calpain 3 (CAPN3) colocalizes with CaMKIIβ at the muscle triad; CAPN3 knockout reduces triad integrity and blunts CaMKIIβ signaling, impairing transcriptional activation of myofibrillar and oxidative metabolism genes in response to exercise and during muscle reloading after atrophy. CaMKIIβ signaling is required for induction of HSP70 and the inflammatory response needed for muscle recovery. CAPN3 knockout mice; hindlimb unloading/reloading model; CaMKIIβ activation measurement; RNA-sequencing; HSP70 expression; immune cell infiltration analysis Human molecular genetics Medium 29528394
2020 CaMKIIβ specifically (among the four CaMKII isoforms) enhances the surface expression and channel activity of the Ca2+-activated chloride channel ANO1 in glioblastoma cells. Gene silencing of CaMKIIβ suppresses ANO1 surface expression and channel activity and reduces migration and invasion of glioblastoma cells. KN-93 pharmacological inhibition; CaMKIIβ siRNA knockdown; heterologous expression of individual CaMKII isoforms; ANO1 surface expression assay; patch-clamp electrophysiology; migration/invasion assays Cells Medium 32357567
2022 ERK1/2 is identified as an important linker downstream of CaMKIIβ affecting synaptic protein expression in hippocampal neurons; CaMKIIβ overexpression or underexpression leads to different profiles of synaptic protein changes, with Mapk3 (ERK1) as a candidate target linking CaMKIIβ dysregulation to synaptogenesis. Lentiviral CaMKIIβ overexpression and knockdown in rat hippocampal neurons; iTRAQ-based quantitative proteomics; immunoblot validation; protein interaction network analysis Neuroscience Low 36041587
2014 Alternative splicing of the CaMKIIβ variable region determines F-actin association in developing neurons: exon E1 is required for F-actin association, while exon E4 assists but is not required. CaMKIIβ isoforms lacking E1 (βe and β'e) do not associate with F-actin microspikes in embryonic cortical neurons. Expression of CaMKIIβ splice variants with and without E1/E4 in E18 rat cortical neurons; co-localization with F-actin microspike structures International journal of clinical and experimental pathology Medium 25031715
2026 Phosphoproteomic analysis of CaMKIIα/CaMKIIβ double-knockout cortical tissue identified 130 proteins with reduced phosphorylation, including 113 not previously known as CaMKII substrates, and provided new in vivo data on the CaMKII substrate consensus sequence. Inducible Camk2a/Camk2b double KO mice; mass spectrometry-based phosphoproteomics; comparison of 5622 phosphopeptides from 2080 proteins ACS chemical neuroscience Medium 41740964
2024 CaMKIIβ hub domain crystal structures reveal coexisting 14-mer and 16-mer assemblies. The CaMKIIβ hub is significantly less thermodynamically stable than the CaMKIIα hub, and larger oligomers are more stable than smaller ones. X-ray crystallography at 3.1 Å (14-mer) and 3.4 Å (16-mer); mass photometry; temperature denaturation experiments; rational mutagenesis to produce dimer Protein science High 38501502

Source papers

Stage 0 corpus · 80 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 CaMKIIbeta functions as an F-actin targeting module that localizes CaMKIIalpha/beta heterooligomers to dendritic spines. Neuron 283 9768845
2012 Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. Cell 253 22579289
2017 De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. American journal of human genetics 153 29100089
2006 CaMKIIbeta association with the actin cytoskeleton is regulated by alternative splicing. Molecular biology of the cell 97 16928958
2016 Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition. Autophagy 91 27245989
2008 CaMKIIbeta binding to stable F-actin in vivo regulates F-actin filament stability. Proceedings of the National Academy of Sciences of the United States of America 84 18840684
2021 CAMK2/CaMKII activates MLKL in short-term starvation to facilitate autophagic flux. Autophagy 73 34282994
2024 Quercetin induces ferroptosis in gastric cancer cells by targeting SLC1A5 and regulating the p-Camk2/p-DRP1 and NRF2/GPX4 Axes. Free radical biology & medicine 71 38190923
2018 De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders. Annals of clinical and translational neurology 70 29560374
2011 A CaMKIIβ signaling pathway at the centrosome regulates dendrite patterning in the brain. Nature neuroscience 68 21725312
2019 CAMK2-Dependent Signaling in Neurons Is Essential for Survival. The Journal of neuroscience : the official journal of the Society for Neuroscience 66 31064859
2020 CaMKIIβ in Neuronal Development and Plasticity: An Emerging Candidate in Brain Diseases. International journal of molecular sciences 52 33019657
2013 CaMKIIβ regulates oligodendrocyte maturation and CNS myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 23785157
2021 Adipocyte CAMK2 deficiency improves obesity-associated glucose intolerance. Molecular metabolism 42 34303021
2014 Generation and behavior characterization of CaMKIIβ knockout mice. PloS one 38 25127391
2022 Distinct phosphorylation states of mammalian CaMKIIβ control the induction and maintenance of sleep. PLoS biology 34 36194579
2017 Regulation of spinogenesis in mature Purkinje cells via mGluR/PKC-mediated phosphorylation of CaMKIIβ. Proceedings of the National Academy of Sciences of the United States of America 34 28607044
2013 CaMKIIβ-mediated LIM-kinase activation plays a crucial role in BDNF-induced neuritogenesis. Genes to cells : devoted to molecular & cellular mechanisms 33 23600483
1991 Efficient transformation of cam2, a behavioral mutant of Paramecium tetraurelia, with the calmodulin gene. Proceedings of the National Academy of Sciences of the United States of America 31 1961754
2015 Capsicum annuum transcription factor WRKYa positively regulates defense response upon TMV infection and is a substrate of CaMK1 and CaMK2. Scientific reports 30 25613640
2021 The dysregulated expression and functional effect of CaMK2 in cancer. Cancer cell international 29 34193145
2017 Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36). Frontiers in molecular neuroscience 27 29311815
2016 The molecular, temporal and region-specific requirements of the beta isoform of Calcium/Calmodulin-dependent protein kinase type 2 (CAMK2B) in mouse locomotion. Scientific reports 25 27244486
1995 Cell adhesion activity of the short cytoplasmic domain isoform of C-CAM (C-CAM2) in CHO cells. FEBS letters 23 7774714
2019 Effects of HIV-1 Tat on oligodendrocyte viability are mediated by CaMKIIβ-GSK3β interactions. Journal of neurochemistry 22 30674062
2018 A novel role for CAMKIIβ in the regulation of cortical neuron migration: implications for neurodevelopmental disorders. Molecular psychiatry 21 29712998
2018 Calpain 3 and CaMKIIβ signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy. Human molecular genetics 20 29528394
2007 Amphetamine sensitization elevates CaMKIIbeta mRNA. Synapse (New York, N.Y.) 20 17603807
2021 Gene-environment interactions mediate stress susceptibility and resilience through the CaMKIIβ/TARPγ-8/AMPAR pathway. iScience 19 34113835
2011 Downregulation of ARFGEF1 and CAMK2B by promoter hypermethylation in breast cancer cells. BMB reports 19 21871176
2020 Severe intellectual disability, absence of language, epilepsy, microcephaly and progressive cerebellar atrophy related to the recurrent de novo variant p.(P139L) of the CAMK2B gene: A case report and brief review. American journal of medical genetics. Part A 17 32875707
2017 Non-canonical heterogeneous cellular distribution and co-localization of CaMKIIα and CaMKIIβ in the spinal superficial dorsal horn. Brain structure & function 16 29151114
2015 Extracellular matrix protein reelin regulate dendritic spine density through CaMKIIβ. Neuroscience letters 16 26003447
2008 Ethanol inhibition of recombinant NMDA receptors is not altered by coexpression of CaMKII-alpha or CaMKII-beta. Alcohol (Fayetteville, N.Y.) 15 18562151
2022 Anti-Tumor Role of CAMK2B in Remodeling the Stromal Microenvironment and Inhibiting Proliferation in Papillary Renal Cell Carcinoma. Frontiers in oncology 14 35127542
2017 Tris (1,3-dichloro-2-propyl) phosphate induces toxicity by stimulating CaMK2 in PC12 cells. Environmental toxicology 13 28181390
2014 Camk2b protects neurons from homocysteine-induced apoptosis with the involvement of HIF-1α signal pathway. International journal of clinical and experimental medicine 13 25126162
2023 Understanding the pathogenetic mechanisms underlying altered neuronal function associated with CAMK2B mutations. Neuroscience and biobehavioral reviews 12 37391113
2022 MiR-24-3p Conservatively Regulates Muscle Cell Proliferation and Apoptosis by Targeting Common Gene CAMK2B in Rat and Cattle. Animals : an open access journal from MDPI 12 35203213
2022 Case Report: Developmental Delay and Acute Neuropsychiatric Episodes Associated With a de novo Mutation in the CAMK2B Gene (c.328G>A p.Glu110Lys). Frontiers in pharmacology 12 35620293
2022 CaMKIIβ knockdown decreases store-operated calcium entry in hippocampal dendritic spines. IBRO neuroscience reports 11 35079728
2018 CaMKIIβ is localized in dendritic spines as both drebrin-dependent and drebrin-independent pools. Journal of neurochemistry 11 29675826
2020 Suppression of CaMKIIβ Inhibits ANO1-Mediated Glioblastoma Progression. Cells 10 32357567
2019 Localization of Retinal Ca2+/Calmodulin-Dependent Kinase II-β (CaMKII-β) at Bipolar Cell Gap Junctions and Cross-Reactivity of a Monoclonal Anti-CaMKII-β Antibody With Connexin36. Frontiers in molecular neuroscience 10 31555090
2021 A familial case of CAMK2B mutation with variable expressivity. SAGE open medical case reports 9 33796307
2024 CaMKIIβ deregulation contributes to neuromuscular junction destabilization in Myotonic Dystrophy type I. Skeletal muscle 8 38769542
2023 Inflammatory Factor IL1α Induces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca2+/CaMK2b Pathway. Neuroscience bulletin 8 37864744
2022 Effects of Camk2b Overexpression and Underexpression on the Proteome of Rat Hippocampal Neurons. Neuroscience 8 36041587
2019 Roles of CaMKIIβ in the neurotoxicity induced by ropivacaine hydrochloride in dorsal root ganglion. Artificial cells, nanomedicine, and biotechnology 8 31317779
2024 Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1 -mutated oral squamous cell carcinoma. Chinese medical journal 7 39227322
2022 GluN1 antibody causes behavioral deficits in prepulse inhibition and memory through CaMKIIβ signaling. Journal of neuroimmunology 7 36417808
2022 Branch point strength controls species-specific CAMK2B alternative splicing and regulates LTP. Life science alliance 7 36543542
2020 A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIβ Signaling in Limb Girdle Muscular Dystrophy. Cell reports. Medicine 7 33205074
2018 Autophosphorylation of F-actin binding domain of CaMKIIβ is required for fear learning. Neurobiology of learning and memory 7 30528771
2024 CAMK2; four genes, one syndrome? Delineation of genotype-phenotype correlations. Current opinion in neurobiology 6 39631163
2023 ERK1/2-Dependent Phosphorylation of GABAB1(S867/T872), Controlled by CaMKIIβ, Is Required for GABAB Receptor Degradation under Physiological and Pathological Conditions. International journal of molecular sciences 6 37686242
2022 Elucidation of pathological mechanism caused by human disease mutation in CaMKIIβ. Journal of neuroscience research 6 35043465
2019 Hypergravity-induced plastic alteration of the vestibulo-sympathetic reflex involves decrease in responsiveness of CAMK2-expressing neurons in the vestibular nuclear complex. The journal of physiological sciences : JPS 6 31435871
2025 Cellular Cholesterol Loss Impairs Synaptic Vesicle Mobility via the CAMK2/Synapsin-1 Signaling Pathway. Frontiers in bioscience (Landmark edition) 5 39862102
2025 Activation of CAMK2 by pseudokinase PEAK1 represents a targetable pathway in triple negative breast cancer. Nature communications 5 39984440
2024 Targeting CAMK2N1/CAMK2 inhibits invasion, migration and angiogenesis of non-small cell lung cancer by promoting autophagy and apoptosis via AKT/mTOR signaling pathway. Gene 5 38490509
2024 Ca2+/CaM dependent protein kinase II (CaMKII)α and CaMKIIβ hub domains adopt distinct oligomeric states and stabilities. Protein science : a publication of the Protein Society 4 38501502
2023 Vascular endothelial growth factor B regulates insulin secretion in β cells of type 2 diabetes mellitus mice via PLCγ and the IP3R‑evoked Ca2+/CaMK2 signaling pathway. Molecular medicine reports 4 37681454
2023 Glucose restriction enhances oxidative fiber formation: A multi-omic signal network involving AMPK and CaMK2. iScience 4 38161415
2014 Alternative splicing in the variable domain of CaMKIIβ affects the level of F-actin association in developing neurons. International journal of clinical and experimental pathology 4 25031715
2025 CaMKIIβ Ca2+ptures ER signals to initiate autophagosome biogenesis. Molecular cell 3 39919714
2025 CaMKIIβ-mediated Phosphorylation Enhances Protein Stability of Spastin to Promote Neurite Outgrowth. The Journal of neuroscience : the official journal of the Society for Neuroscience 3 40645772
2025 CAMK2B Impacts the Proliferation, Invasion, and Migration of Glioma Cells via the Ras/Raf/MEK/ERK Signaling Pathway. Oncology research 3 41050075
2016 Phorbol ester-mediated re-expression of endogenous LAT adapter in J.CaM2 cells: a model for dissecting drivers and blockers of LAT transcription. Genes and immunity 3 27278128
2025 The Protective Effect of Annexin A1 on Autophagy Via the CAMK2/BECN1 Signaling Pathway in PC12 Cells Stimulated with H2O2. Neurotoxicity research 2 40272685
2025 The m6A reader IGF2BP3 facilitates myogenesis by activating the CAMK2B-MEF2C axis. International journal of biological macromolecules 2 40683492
2023 Super-resolution imaging reveals the relationship between CaMKIIβ and drebrin within dendritic spines. Neuroscience research 2 37659612
2024 Feed-forward stimulation of CAMK2 by the oncogenic pseudokinase PEAK1 generates a therapeutically "actionable" signalling axis in triple negative breast cancer. bioRxiv : the preprint server for biology 1 38405732
2023 A CAMK2B variant associated with tetralogy of Fallot, developmental delay, and growth retardation. European journal of medical genetics 1 37734707
2021 Adeno-associated virus-mediated expression of an inactive CaMKIIβ mutant enhances muscle mass and strength in mice. Biochemical and biophysical research communications 1 34922202
2026 CAMK2 Expression and Its Regulation on Testosterone Synthesis in Mouse Testis. Biological & pharmaceutical bulletin 0 41638654
2026 Phosphoproteomic Analysis of Cortical Tissue from Mice Lacking Both CaMKIIα and CaMKIIβ Identifies Novel In Vivo Substrates. ACS chemical neuroscience 0 41740964
2026 CaMKIIβ insufficiency disrupts cortical networks, producing aberrant low-gamma oscillations and seizure susceptibility. Epilepsia 0 41984532
2024 Severe Developmental Delay and Behavior Abnormalities in a Patient with De Novo CAMK2B Mutation: A Case Report and Literature Review. Annals of Indian Academy of Neurology 0 39113374
2024 Hypoxia Modulates Sodium Chloride Co-transporter via CaMKII-β Pathway: An In Vitro Study with mDCT15 Cells. Life (Basel, Switzerland) 0 39459529

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