Affinage

CAMKK2

Calcium/calmodulin-dependent protein kinase kinase 2 · UniProt Q96RR4

Length
588 aa
Mass
64.7 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CaMKK2 is a Ca²⁺/calmodulin-activated serine/threonine kinase that transduces intracellular Ca²⁺ signals into the activation of downstream kinases, principally AMPK and the CaMKI/CaMKIV cascade, thereby coupling Ca²⁺ flux to energy sensing, transcription, cytoskeletal dynamics, and cell-fate decisions across multiple tissues (PMID:18460329, PMID:26050738). Isoform-selective drug-resistant mutants establish CaMKK2 as the kinase responsible for Ca²⁺-stimulated phosphorylation of AMPKα at Thr172, while it shares CaMKIV phosphorylation with CaMKKα (PMID:26050738); it also directly phosphorylates Akt at Thr-308 in a Ca²⁺/CaM-dependent manner (PMID:28634229). Activity is gated by autophosphorylation at Thr85, which confers autonomous Ca²⁺-independent activity as a form of molecular memory (PMID:26395653), and is switched off by PKA phosphorylation at Ser100/Ser495/Ser511 coupled to 14-3-3 recruitment that locks the kinase in a dephosphorylation-resistant inhibited state (PMID:32913128, PMID:29649512, PMID:33146997). Through AMPK, CaMKK2 governs hypothalamic appetite control via NPY/AgRP (PMID:18460329), amino-acid- and genotoxic-stress-driven autophagy and cell-cycle arrest via ULK1 and nuclear AMPKα1 (PMID:23027865, PMID:29133590), hepatic gluconeogenesis (PMID:22240810), and adipogenic and granulocytic differentiation programs (PMID:21862616, PMID:21816924). CaMKK2 localizes to focal adhesions and caveolar Cav1.2 complexes, where it drives AMPK–VASP-dependent actomyosin assembly and CaMK1a-mediated excitation–transcription coupling, respectively (PMID:29972773, PMID:35412911). In disease, Aβ42-driven over-activation of the CaMKK2–AMPK dyad mediates synaptic loss through Tau-S262, MFF, and ULK2 phosphorylation (PMID:23583109, PMID:35915085), and CaMKK2 supports multiple cancers through AMPK-dependent and AMPK-independent (lipogenic, PDE1A–PKG1–VASP) routes (PMID:30242113, PMID:37335130), including immunosuppressive functions in intratumoral myeloid cells (PMID:31164648). Notably, CaMKK2 protein is undetectable in adult murine skeletal muscle and is dispensable for contraction-stimulated AMPK activation there (PMID:37380024).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2008 High

    Established CaMKK2 as the physiological upstream AMPK kinase in hypothalamic energy-sensing neurons, defining its role in appetite regulation.

    Evidence CaMKK2 knockout mice with pharmacological inhibition and co-IP of an AMPK signaling complex, with NPY/AgRP readouts

    PMID:18460329

    Open questions at the time
    • Did not define the molecular architecture of the CaMKK2-AMPK complex
    • Upstream Ca²⁺ sources in these neurons not resolved
  2. 2009 High

    Demonstrated that CaMKK2 acts through CaMKIV to drive CREB-dependent BDNF transcription, linking the kinase to developmental transcriptional programs.

    Evidence CaMKK2 and CaMKIV null mice with BDNF rescue of cerebellar granule cell migration and pCREB immunostaining

    PMID:19605628

    Open questions at the time
    • Direct CaMKIV substrate phosphorylation by CaMKK2 not biochemically isolated here
    • Ca²⁺ trigger upstream not defined
  3. 2011 High

    Defined CaMKK2 as a cell-intrinsic, kinase-activity-dependent brake on granulocyte and adipocyte differentiation via AMPK, extending its role to lineage commitment.

    Evidence Camkk2-/- mice, BMT rescue, kinase-dead epistasis in 32D cells, and AMPK-rescue in preadipocytes

    PMID:21816924 PMID:21862616

    Open questions at the time
    • Ca²⁺ signals controlling lineage-specific CaMKK2 activation unknown
    • Direct AMPK substrates in differentiation not identified
  4. 2012 High

    Showed CaMKK2 controls hepatic gluconeogenesis and links androgen-receptor signaling to a feed-forward proliferative loop in prostate cancer, broadening its metabolic and oncogenic reach.

    Evidence Liver-specific Cre-lox deletion with glucose-production assays; siRNA and DHT stimulation in LNCaP cells with AR reporter and cell-cycle analysis

    PMID:22240810 PMID:22654108

    Open questions at the time
    • HDAC5 phosphorylation link to PGC-1α stated as mechanism 'may involve'
    • Direct kinase substrates in AR loop not defined
  5. 2012 High

    Placed CaMKK2-β upstream of AMPK and mTORC1 in amino-acid-starvation autophagy, connecting Ca²⁺ to ULK1-Ser555 phosphorylation.

    Evidence siRNA, STO-609, Ca²⁺ chelation, and ULK1 phosphorylation assays

    PMID:23027865

    Open questions at the time
    • Source distinction between extracellular and store Ca²⁺ not fully resolved
    • Mechanism of mTORC1 inactivation not detailed
  6. 2013 High

    Connected CaMKK2-AMPK to Alzheimer's pathology by showing Ca²⁺-driven, CaMKK2-dependent AMPK phosphorylation of Tau-S262 mediates Aβ-induced spine loss.

    Evidence Neuronal knockdown/overexpression, pharmacological inhibition, APP transgenic mouse, Tau S262A rescue and spine counting

    PMID:23583109

    Open questions at the time
    • Whether Tau S262 is a direct AMPK substrate in vivo not isolated biochemically
    • Reversibility of synaptic loss not addressed
  7. 2015 High

    Defined the activity-state machinery of CaMKK2: Thr85 autophosphorylation generates autonomous activity (molecular memory), with a disease-linked T85S mutation and behavioral phenotypes in null mice.

    Evidence In vitro autophosphorylation, T85S mutagenesis, lithium rescue, and behavioral assays in CaMKK2 null mice

    PMID:26395653

    Open questions at the time
    • Human disease causality of T85S not established by genetics
    • Structural basis of autonomous activity not solved
  8. 2015 High

    Established CaMKK2 as a scaffold coupling CaMKIV to mTOR/S6K for protein synthesis in liver cancer, and confirmed kinase-activity dependence.

    Evidence RNAi, kinase-inactive mutant rescue, STO-609, and in vivo tumor models

    PMID:25847065

    Open questions at the time
    • Direct interaction surfaces of the scaffold not mapped
    • Distinction between scaffold and catalytic contributions incomplete
  9. 2016 High

    Resolved that elevated Ca²⁺ engages CaMKK2-AMPK to enforce G1 arrest in LKB1-null tumors, positioning CaMKK2 as an alternative AMPK-activating axis.

    Evidence LKB1-null cells, constitutively active CaMKK2, dominant-negative AMPK, CRISPR AMPKα double KO, cell-cycle analysis

    PMID:27141100

    Open questions at the time
    • Source of Ca²⁺ elevation in LKB1-null cells unresolved
    • Did not assess Akt or CaMKIV branches
  10. 2017 High

    Showed CaMKK2 directly phosphorylates Akt at Thr-308, revealing a substrate beyond the canonical AMPK/CaMK cascade.

    Evidence In vitro kinase assay with recombinant CaMKK2 and Akt plus cellular epistasis with PDK1 knockdown in ovarian cancer cells

    PMID:28634229

    Open questions at the time
    • Single lab; reciprocal in vivo confirmation limited
    • Relative contribution versus PDK1 across cell types unknown
  11. 2017 Medium

    Identified metabolite-level control of CaMKK2, with GDH1-derived α-ketoglutarate enhancing CaMKK2-AMPK binding to confer anoikis resistance.

    Evidence Reciprocal Co-IP, RNAi, pharmacological inhibition, and patient-derived xenografts

    PMID:29249655

    Open questions at the time
    • Single lab; structural basis of αKG-enhanced binding unknown
    • Direct binding of αKG to CaMKK2 not shown
  12. 2017 High

    Demonstrated nuclear-restricted CaMKK2-AMPKα1 activation by genotoxic stress, independent of ATM and LKB1, defining a compartmentalized DNA-damage survival pathway.

    Evidence STO-609, AMPKα double KO, subcellular fractionation, Ca²⁺ chelation, and viability assays

    PMID:29133590

    Open questions at the time
    • Mechanism of nuclear Ca²⁺ generation unresolved
    • Nuclear AMPK substrates not enumerated
  13. 2018 High

    Defined the inhibitory regulatory mechanism: 14-3-3 binds the CaMKK2 kinase domain and N-terminal phospho-sites and slows dephosphorylation without blocking catalysis.

    Evidence Enzyme activity, SAXS, time-resolved fluorescence, phosphopeptide crystallography

    PMID:29649512

    Open questions at the time
    • Full-length CaMKK2/14-3-3 complex structure not solved
    • Physiological kinase generating Thr145 phosphorylation not defined here
  14. 2018 High

    Localized CaMKK2 to focal adhesions and established its AMPK-VASP-dependent control of mechanosensitive contractile stress fiber assembly.

    Evidence Localization imaging, pharmacological inhibition of CaMKK2 and Ca²⁺ channels, VASP phosphorylation, traction force microscopy

    PMID:29972773

    Open questions at the time
    • Mechanosensitive channel identity not specified
    • Whether VASP is a direct AMPK substrate not isolated
  15. 2018 High

    Revealed an AMPK-independent oncogenic function: CaMKK2 promotes lipogenesis (ACC/FASN) post-transcriptionally, opposite to AMPK's lipogenesis-suppressing role in prostate cancer.

    Evidence Camkk2 and AMPKβ1 deletion in Pten-null prostate cancer model with lipogenesis and protein expression analysis

    PMID:30242113

    Open questions at the time
    • Molecular mechanism of post-transcriptional ACC/FASN control undefined
    • Direct CaMKK2 effector in this pathway unidentified
  16. 2019 High

    Extended CaMKK2 function to the tumor microenvironment, showing macrophage CaMKK2 drives immunosuppression and limits CD8+ T cell recruitment.

    Evidence Conditional Camkk2-/- mice, BMT, macrophage-T cell co-culture, pharmacological inhibition, flow cytometry

    PMID:31164648

    Open questions at the time
    • Downstream kinase effectors in macrophages not defined
    • Chemokine regulation mechanism not resolved
  17. 2020 High

    Solved the PKA-driven OFF-switch: phosphorylation at Ser495 impairs Ca²⁺/CaM activation while Ser100/Ser511 recruit 14-3-3 to lock CaMKK2 inactive, with a cooperative-binding crystal structure.

    Evidence In vitro kinase assays, mutagenesis, 14-3-3ζ/CaMKK2 peptide crystallography, cellular PKA stimulation

    PMID:32913128

    Open questions at the time
    • Phosphatase counteracting these sites not identified
    • In vivo physiological triggers of PKA inactivation not mapped
  18. 2020 High

    Demonstrated pharmacological stabilization of the 14-3-3/CaMKK2 inhibited state by fusicoccanes, validating 14-3-3 as a tunable regulatory interface.

    Evidence Ternary complex crystal structures, fluorescence polarization, and phosphorylation-mediated inhibition assays with full-length CaMKK2

    PMID:33146997

    Open questions at the time
    • Cellular and in vivo efficacy of fusicoccanes on CaMKK2 not shown
    • Selectivity across 14-3-3 client kinases not addressed
  19. 2020 Medium

    Broadened CaMKK2 outputs to membrane trafficking and metabolite/cofactor sensing, including CaMK4-dependent transferrin/iron handling and direct BH4 binding driving AMPK/CREB/PGC-1α.

    Evidence CRISPR KO HEK293 cells and CAMK4-/- mice for transferrin trafficking; direct BH4 binding assay and diabetic cardiomyopathy models

    PMID:32460794 PMID:32699151

    Open questions at the time
    • Single-lab studies
    • Direct CaMKK2 substrate in transferrin trafficking not defined
    • BH4 binding site on CaMKK2 not mapped
  20. 2021 Medium

    Established additional cancer-promoting axes for CaMKK2: AR-driven AMPK-ULK1 autophagy, AMPK-NRF2 ferroptosis suppression, and CAF macropinocytosis, plus a COPI/Gemin4 endomembrane link.

    Evidence Genetic/pharmacological CAMKK2 disruption in CRPC and melanoma models, CAF macropinocytosis assays, and proteomic identification of Gemin4/COPI interaction

    PMID:33531625 PMID:33653692 PMID:34242660 PMID:34725334

    Open questions at the time
    • COPI mechanistic link to CaMKK2 inferred rather than direct
    • Some readouts single-lab
    • Direct substrates in these pathways unidentified
  21. 2022 High

    Resolved compartmentalized Ca²⁺-to-transcription coupling: a caveolar Cav1.2/CaMKK2/CaMK1a complex drives CREB-dependent vascular remodeling genes.

    Evidence Live Ca²⁺ imaging, reciprocal Co-IP, caveolin1-KO mice, STO-609, and mesenteric artery pressure model

    PMID:35412911

    Open questions at the time
    • Stoichiometry and assembly determinants of the complex unknown
    • Generalizability beyond vascular myocytes unaddressed
  22. 2022 High

    Mechanistically detailed Aβ-driven synaptotoxicity, with CaMKK2-AMPK over-activation coordinating MFF-dependent mitochondrial fission and ULK2-dependent mitophagy.

    Evidence Transgenic AD mice, human APP knockin ES-derived neurons, AMPK subunit KO, and MFF/ULK2 phosphorylation assays

    PMID:35915085

    Open questions at the time
    • Direct phosphorylation of MFF/ULK2 by AMPK in this context not isolated biochemically
    • Therapeutic reversibility not tested
  23. 2023 High

    Defined a non-canonical actin-regulatory metastasis pathway, CaMKK2-PDE1A-PKG1-VASP, distinct from the AMPK-VASP axis.

    Evidence Genetic/pharmacological CaMKK2 disruption, PDE1A and cGMP/PKG1 assays, VASP phosphorylation, and TNBC/HGSOC xenograft metastasis models

    PMID:37335130

    Open questions at the time
    • Mechanism by which CaMKK2 raises PDE1A expression unknown
    • Relationship to the AMPK-VASP focal adhesion pathway not reconciled
  24. 2023 High

    Identified Cdo1 as a physical tether assembling CaMKK2 with AMPK in hepatocytes to drive exercise-responsive fatty-acid oxidation and mitochondrial biogenesis.

    Evidence Hepatocyte-specific Cdo1 KO/OE, Co-IP of Cdo1-CaMKK2-AMPK complex, and exercise mouse model

    PMID:38110408

    Open questions at the time
    • Structural basis of the trimeric tether unknown
    • Generality across other tissues unaddressed
  25. 2023 High

    Corrected the tissue scope of CaMKK2 by showing it is absent and functionally dispensable in adult murine skeletal muscle, refuting earlier inhibitor-based claims.

    Evidence Selective inhibitor SGC-CAMKK2-1, CaMKK2 KO mice, ex vivo contraction assays, and proteomic/mass-spec negative detection

    PMID:37380024

    Open questions at the time
    • Does not resolve which kinase mediates contraction-stimulated AMPK activation in muscle
    • Species/developmental-stage generalization untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CaMKK2 substrate choice (AMPK vs CaMKI/IV vs Akt) and scaffold-versus-catalytic functions are selected in a given cell, and how diverse Ca²⁺/metabolite inputs are integrated at the kinase, remain unresolved.
  • No unified structural model coupling activation inputs to substrate selection
  • Tissue-specific determinants of AMPK-dependent versus AMPK-independent outputs undefined
  • Direct in vivo substrate repertoire incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005886 plasma membrane 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 3 R-HSA-168256 Immune System 2
Partners
AKT1CACNA1CCAMK4CDO1PRKAA1PRKAA2YWHAGYWHAZ
Complex memberships
CaMKK2-AMPK signaling complexCav1.2/CaMKK2/CaMK1a caveolar complexCdo1-CaMKK2-AMPK complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 CaMKK2 functions as an AMPKα kinase in the hypothalamus and forms a unique signaling complex with AMPKα and AMPKβ subunits. Acute pharmacological inhibition of CaMKK2 in wild-type but not CaMKK2 null mice inhibits appetite and reduces NPY/AgRP mRNAs, establishing CaMKK2 as an upstream activator of AMPK in hypothalamic energy-sensing neurons. CaMKK2 knockout mice, pharmacological inhibition (STO-609), co-immunoprecipitation of signaling complex, NPY/AgRP mRNA measurement Cell metabolism High 18460329
2013 NMDA receptor activation or membrane depolarization raises intracellular Ca²⁺, which activates AMPK in a CAMKK2-dependent manner in cortical/hippocampal neurons. AMPK then phosphorylates Tau on the KxGS motif S262, and Aβ42 oligomer-induced dendritic spine loss is blocked by inhibiting CAMKK2 or AMPK, or by expressing Tau S262A. Neuronal knockdown/overexpression of CAMKK2 and AMPK, pharmacological inhibition, in vivo APP transgenic mouse model, dendritic spine counting Neuron High 23583109
2017 GDH1-derived α-ketoglutarate activates CaMKK2 by enhancing its binding to the substrate AMPK, placing CaMKK2 downstream of GDH1 and upstream of AMPK in LKB1-deficient lung cancer cells to provide anoikis resistance. Co-immunoprecipitation, RNAi knockdown, pharmacological inhibition, patient-derived xenograft models Molecular cell Medium 29249655
2015 CaMKK2 signals through CaMKIV to control liver cancer cell growth, and serves as a scaffold to assemble CaMKIV with components of the mTOR/S6K pathway, stimulating protein synthesis. Kinase-inactive CaMKK2 mutants fail to rescue growth defects from CaMKK2 loss, demonstrating kinase-activity dependence. RNAi knockdown, ectopic expression of wild-type vs. kinase-inactive mutants, in vivo tumor models, STO-609 pharmacological inhibition Hepatology High 25847065
2017 CaMKK2 directly phosphorylates Akt at Thr-308 in a Ca²⁺/CaM-dependent manner, as shown by in vitro reconstitution with recombinant CaMKK2 and recombinant Akt. In ovarian cancer cells, CaMKK2 knockdown or inhibition reduces Akt phosphorylation at Thr-308 and Ser-473 additively with PDK1 knockdown. In vitro kinase assay with recombinant proteins, siRNA knockdown, pharmacological inhibition, intracellular Ca²⁺ chelation The Journal of biological chemistry High 28634229
2012 Essential amino acid withdrawal raises cytosolic Ca²⁺ from extracellular medium and intracellular stores, activating AMPK via CaMKK-β, which then phosphorylates ULK1 at Ser-555 to initiate autophagy. CaMKK-β is also required for mTORC1 inactivation under amino acid starvation. siRNA knockdown of CaMKK-β and AMPK, pharmacological inhibition (STO-609), Ca²⁺ chelation, ULK1 phosphorylation assay The Journal of biological chemistry High 23027865
2022 Aβ42 oligomer-driven over-activation of the CAMKK2-AMPK kinase dyad mediates synaptic loss through coordinated phosphorylation of MFF (driving mitochondrial fission) and ULK2 (driving mitophagy). Spatially restricted structural remodeling of dendritic mitochondria in CA1 apical tufts was CAMKK2-AMPK-dependent. Transgenic AD mouse model, human APP knockin ES cell-derived neurons, genetic KO of AMPK subunits, phosphorylation assays for MFF and ULK2 Nature communications High 35915085
2019 CaMKK2 is highly expressed in intratumoral myeloid cells in breast cancer. CaMKK2 deletion in macrophages reduces their ability to suppress T cell proliferation and increases chemokine expression that recruits effector CD8+ T cells; CaMKK2 inhibition blocks tumor growth in a CD8+ T cell-dependent manner. Conditional Camkk2-/- mice, BMT, in vitro macrophage-T cell co-culture suppression assays, pharmacological inhibition, flow cytometry Nature communications High 31164648
2021 CaMKK2 and AMPK promote macropinocytosis in pancreatic cancer-associated fibroblasts downstream of cytosolic Ca²⁺ elevation and in cooperation with ARHGEF2; macropinocytosis supports CAF fitness and provides secreted amino acids that promote tumor cell survival. Genetic knockdown of CaMKK2 and ARHGEF2, pharmacological inhibition, Ca²⁺ measurements, macropinocytosis assays, in vivo PDAC tumor models Cancer discovery High 33653692
2009 CaMKK2 and CaMKIV are required for CREB phosphorylation in cerebellar granule cells, which drives Bdnf transcription necessary for granule cell migration from the external to internal granule cell layer. Re-expression of CaMKK2 in null neurons restores pCREB and BDNF, and exogenous BDNF rescues migration defects in vitro. CaMKK2 null and CaMKIV null mice, in vivo/in vitro cerebellar development assays, rescue by BDNF addition, pCREB immunostaining The Journal of neuroscience High 19605628
2020 PKA signaling inactivates CaMKK2 by phosphorylating three conserved serine residues: Ser495 directly impairs Ca²⁺-calmodulin activation; Ser100 and Ser511 mediate recruitment of 14-3-3 adaptor proteins that maintain CaMKK2 in the inactivated state by preventing dephosphorylation of phospho-Ser495. Crystal structure of 14-3-3ζ bound to a diphosphorylated CaMKK2 peptide reveals cooperative binding at canonical (Ser511) and noncanonical (Ser100) sites. In vitro kinase assays, site-directed mutagenesis, protein crystallography (crystal structure of 14-3-3ζ/CaMKK2 peptide complex), cellular PKA stimulation The Journal of biological chemistry High 32913128
2018 14-3-3γ directly interacts with the kinase domain of CaMKK2 and the region containing the inhibitory phosphorylation site Thr145 in the N-terminal extension. 14-3-3 binding does not inhibit catalytic activity of phosphorylated CaMKK2 but slows its dephosphorylation. Crystal structures of phosphopeptides containing CaMKK2 14-3-3 binding motifs bound to 14-3-3 were determined. Enzyme activity measurements, SAXS, time-resolved fluorescence spectroscopy, protein crystallography, phosphopeptide binding assays Biochimica et biophysica acta. General subjects High 29649512
2016 In LKB1-null tumor cells, elevated intracellular Ca²⁺ activates CAMKK2, which phosphorylates AMPK-α at Thr172 causing G1 cell-cycle arrest. Expression of a truncated, Ca²⁺/calmodulin-independent CAMKK2 mutant phenocopies LKB1 re-expression. Dominant-negative AMPK or double AMPK-α KO prevents Ca²⁺-induced G1 arrest, placing CAMKK2 upstream of AMPK in this pathway. LKB1-null cell lines, constitutively active CAMKK2 expression, dominant-negative AMPK, CRISPR double KO of AMPK-α1/α2, Ca²⁺ ionophore treatment, cell-cycle analysis Molecular cancer research High 27141100
2017 Genotoxic stress (etoposide) activates the AMPK-α1 isoform specifically within the nucleus via nuclear Ca²⁺ increase and CaMKK2; activation is independent of ATM and LKB1. Nuclear AMPK-α1 activation promotes G1 arrest and enhances cell survival after etoposide, effects abolished by AMPK-α1/α2 double KO. Pharmacological inhibition (STO-609), AMPK-α1/α2 double KO, subcellular fractionation, Ca²⁺ chelation, cell-cycle analysis, viability assays Molecular cancer research High 29133590
2022 A molecular complex of Cav1.2/CaMKK2/CaMK1a forms within caveolae of vascular myocytes. Ca²⁺ influx through Cav1.2 directly activates CaMKK2; CaMKK2 then phosphorylates CaMK1a, which translocates to the nucleus to phosphorylate CREB, driving expression of genes involved in chemotaxis, leukocyte adhesion, and vascular remodeling. Disruption of caveolae or CaMKK2 inhibition abrogates these effects. Live Ca²⁺ imaging with genetically encoded indicators, co-immunoprecipitation of Cav1.2/CaMKK2/CaMK1a complex, caveolin1-KO mice, STO-609 pharmacological inhibition, mesenteric artery pressure loading model PNAS High 35412911
2015 Thr85 is a CaMKK2 autophosphorylation site that generates autonomous (Ca²⁺-independent) activity, providing molecular memory of prior Ca²⁺ stimulation. The disease-linked T85S mutation fails to generate autonomous activity upon phosphorylation at Ser85, causing partial loss of CaMKK2 activity. Lithium (GSK3 inhibitor) rescues autonomous activity in the T85S mutant. CaMKK2 null mice display anxiety and manic-like behavioral disturbances. In vitro autophosphorylation assays, site-directed mutagenesis (T85S), autonomous activity measurements, GSK3 inhibition with lithium, behavioral assays in CaMKK2 null mice Scientific reports High 26395653
2018 CaMKK2 localizes around focal adhesions at the ends of contractile stress fibers and is enriched at sites of mechanosensitive Ca²⁺ influx. CaMKK2 acts upstream of AMPK to phosphorylate VASP, inhibiting actin polymerization at focal adhesions and enabling contractile stress fiber maturation. Inhibition of CaMKK2 or mechanosensitive Ca²⁺ channels impairs AMPK and VASP phosphorylation and abolishes contractile bundles. Subcellular localization imaging, pharmacological inhibition of CaMKK2 and Ca²⁺ channels, AMPK and VASP phosphorylation assays, traction force microscopy Cell reports High 29972773
2020 CaMKK2/AMPK signaling is required for assembly and maintenance of peripheral actomyosin bundles at epithelial cell-cell contacts; these bundles arise from lateral fusion of transverse arc stress fibers. Inhibition of CaMKK2/AMPK disrupts tension-maintaining actomyosin bundles, redistributes cellular forces, and causes defects in monolayer integrity and epithelial identity. Pharmacological inhibition of CaMKK2 and AMPK, live-cell imaging of actin dynamics, traction force microscopy, monolayer integrity assays Cell reports High 32209483
2012 In prostate cancer, the androgen receptor (AR) induces CaMKK2 mRNA/protein expression and causes nuclear translocation of CaMKK2. CaMKK2 in turn maintains AR transcriptional activity (PSA expression, AR response element-driven reporter), cyclin D1, and Rb hyperphosphorylation. Loss of CaMKK2 reduces cell proliferation and causes G1 arrest, establishing an AR-CaMKK2 feedback loop. siRNA knockdown of CaMKK2, dihydrotestosterone stimulation, androgen withdrawal, reporter assays, cell-cycle analysis, LNCaP cells The Journal of biological chemistry High 22654108
2011 CaMKK2 is expressed in preadipocytes where it acts as an AMPKα kinase. Inhibition or deletion of CaMKK2 in preadipocytes accelerates adipogenic differentiation by reducing Pref-1 and Sox9 mRNA, releasing suppression of C/EBPβ and C/EBPδ. AMPK activation reverses the enhanced differentiation caused by CaMKK2 loss. CaMKK2 null preadipocytes, AICAR-mediated AMPK activation rescue, mRNA expression analysis, adipogenesis assays Endocrinology High 21862616
2012 CaMKK2 is expressed in liver and its liver-specific deletion lowers blood glucose and improves glucose tolerance. CaMKK2 KO hepatocytes produce less glucose, show decreased mRNA for PGC-1α and gluconeogenic enzymes (G6Pase, PEPCK), and fail to respond to catecholamine stimulation. The mechanism may involve diminished HDAC5 phosphorylation necessary for PGC-1α promoter derepression. Liver-specific Cre-lox CaMKK2 deletion, primary hepatocyte isolation, glucose production assays, qRT-PCR, adrenergic stimulation, HDAC5 phosphorylation Molecular endocrinology High 22240810
2011 CaMKK2 functions as a cell-intrinsic inhibitor of granulocytic fate commitment in myeloid progenitors. CaMKK2 null bone marrow produces excess mature granulocytes; re-expression of CaMKK2 in null CMPs rescues aberrant granulopoiesis. Overexpression of CaMKK2 in 32D myeloblasts impedes G-CSF-induced granulocyte differentiation in a kinase-activity-dependent manner. Camkk2-/- mice, bone marrow transplantation, ectopic CaMKK2 expression (wild-type vs. kinase-dead), 32D differentiation assays, flow cytometry Journal of leukocyte biology High 21816924
2011 PKA pathway promotes inclusion of CaMKK2 exon 16, generating two splice variants (with/without exon 16) that are differentially phosphorylated by PKA and have distinct effects on neuronal morphology: the +E16 variant promotes neurite branching while the -E16 variant promotes neurite elongation. CaMKKβ1 is required for forskolin-induced neurite growth. Alternative splicing reporter assays, PKA selective inhibitor H89, RNAi knockdown, overexpression in B35 neuroblastoma cells, neurite morphology analysis RNA biology Medium 21957496
2016 CaMKK2 suppresses muscle regeneration by inhibiting myoblast proliferation and differentiation in an AMPK-dependent manner. CaMKK2 overexpression causes AMPK-mediated cell-cycle arrest (Cdc2-Tyr15 phosphorylation) and represses PGC-1α transcription to suppress differentiation; overexpression of CaMKK2 in mouse muscle by electroporation impairs freeze injury-induced regeneration. Overexpression and knockdown of CaMKK2 in C2C12 myoblasts, AMPK agonist/antagonist, in vivo electroporation of CaMKK2, freeze injury model International journal of molecular sciences Medium 27783047
2018 CAMKK2 promotes prostate cancer independently of AMPK via increased lipogenesis: CAMKK2 deletion reduces expression of ACC and FASN by a post-transcriptional mechanism (potentially decreased protein translation), while AMPK activation opposes this by inhibiting lipogenesis. CAMKK2 and AMPK thus have opposing effects on lipogenesis and prostate cancer progression. Genetic Camkk2 deletion in Pten-null mouse prostate cancer model, AMPKβ1 deletion, human PCa cell lines, lipogenesis assays, protein expression analysis Cancer research High 30242113
2021 AR-driven CaMKK2-AMPK-ULK1 signaling promotes autophagy in prostate cancer in an mTOR-independent manner. Inhibition of CAMKK2 disrupts autophagy and impairs tumor growth in multiple CRPC mouse models; AMPK-ULK1 inhibition also blocks autophagy and colony formation. Genetic and pharmacological disruption of CAMKK2, AMPK, and ULK1; autophagy flux assays; CRPC mouse models; patient tumor sample analysis Oncogene High 33531625
2023 CaMKK2 mediates actin cytoskeletal dynamics to promote metastasis through a CaMKK2-PDE1A-PKG1-VASP pathway: CaMKK2 increases expression of phosphodiesterase PDE1A, which hydrolyzes cGMP to decrease PKG1 activity; reduced PKG1 activity decreases VASP phosphorylation, and hypophosphorylated VASP binds F-actin to promote cell movement. Genetic disruption and pharmacological inhibition of CaMKK2, PDE1A expression analysis, cGMP/PKG1 activity assays, VASP phosphorylation, murine xenograft metastasis models of TNBC and HGSOC Cancer research High 37335130
2020 CAMKK2-CAMK4 signaling regulates receptor-mediated transferrin trafficking and iron homeostasis. Loss of CAMK4 causes abnormal post-translational modifications and turnover of transferrin in cerebellum and liver. CAMKK2/CAMK4 deletion in HEK293 cells alters intracellular Ca²⁺ homeostasis and disrupts molecular interactions of transferrin with its receptor-associated protein complexes. CAMK4-/- mice, CRISPR/Cas9-deleted CAMKK2 and/or CAMK4 HEK293 cells, transferrin trafficking assays, Ca²⁺ measurements, protein interaction analysis Cell communication and signaling Medium 32460794
2021 CaMKK2 knockdown leads to identification of Gemin4 as a direct interactor of CaMKK2 capable of also binding COPI subunits. CaMKK2 knockdown reduces δ-COP protein and causes Golgi expansion, ER stress, abortive autophagy, and impaired lysosomal acidification—phenotypes of COPI depletion—suggesting CaMKK2 sustains cell proliferation through effects on endomembrane trafficking. CAMKK2 knockdown, proteomics identification of interactors, co-immunoprecipitation with COPI subunits, imaging of Golgi and lysosomes, ER stress assays Cell death & disease Medium 34725334
2020 Fusicoccin A and related fusicoccanes stabilize the interaction between 14-3-3γ and a diphosphorylated CaMKK2 peptide, enhancing binding affinity of full-length phosphorylated CaMKK2 to 14-3-3γ and slowing CaMKK2 dephosphorylation, thereby maintaining CaMKK2 in its phosphorylation-mediated inhibited state. Crystal structures of ternary 14-3-3/fusicoccane/CaMKK2-peptide complexes were determined. Crystal structures of ternary complexes, fluorescence polarization binding assays, phosphorylation-mediated inhibition assays with full-length CaMKK2 ACS chemical biology High 33146997
2021 CAMKK2 negatively regulates ferroptosis in melanoma by activating the AMPK-NRF2 pathway to suppress lipid peroxidation. CAMKK2 is activated during ferroptosis and its suppression increases ferroptosis inducer efficacy and anti-PD-1 immunotherapy response. CAMKK2 knockdown/overexpression, AMPK and NRF2 pathway analysis, lipid peroxidation assays, xenograft tumor models The Journal of investigative dermatology Medium 34242660
2023 Cdo1 (cysteine dioxygenase type 1) tethers CaMKK2 to AMPK by physically interacting with both proteins, thereby activating AMPK signaling to promote fatty acid oxidation and mitochondrial biogenesis in hepatocytes. Hepatocyte-specific Cdo1 KO impairs exercise-induced AMPK activation and worsens NAFLD. Hepatocyte-specific KO and overexpression of Cdo1, co-immunoprecipitation demonstrating Cdo1-CaMKK2-AMPK complex, AMPK activity assays, exercise intervention mouse model Nature communications High 38110408
2020 Tetrahydrobiopterin (BH4) directly binds CaMKK2 and activates downstream AMPK/CREB/PGC-1α signaling to rescue mitochondrial and cardiac dysfunction in diabetic cardiomyopathy. Proteomics identified oxidative phosphorylation as the BH4-targeted pathway via CaMKK2. Proteomics, direct BH4-CaMKK2 binding assay, AMPK phosphorylation assays, rodent diabetic cardiomyopathy models, mitochondrial function assays Life science alliance Medium 32699151
2021 CAMKK2 regulates mitochondrial function in a cell-type-specific manner by controlling expression, post-translational modifications, and megacomplex assembly of succinate dehydrogenase (SDH) subunit B (SDHB); CAMKK2 deletion suppresses cellular respiration and shifts metabolism toward aerobic glycolysis (Warburg effect) in both HEK293 and HepG2 cells. CRISPR/Cas9 CAMKK2 KO, oxygen consumption rate measurements, SDH enzyme activity assays, SDHB knockdown/overexpression, mitochondrial supercomplex analysis, proteomics Cell communication and signaling Medium 34563205
2016 Wnt5a activates the CaMKK-CaMKIα cascade to specifically promote axonal (but not dendritic) outgrowth during neuronal polarization. Pharmacological and genetic inhibition of CaMKK-CaMKIα abolishes Wnt5a-induced axonal elongation; rescue of CaMKIα in CaMKIα-knockdown neurons restores Wnt5a-mediated axon outgrowth. Ca²⁺ imaging in cortical slices, pharmacological CaMKK inhibition, CaMKIα genetic knockdown and rescue, neuronal morphology analysis Molecular brain Medium 26772170
2023 CaMKK2 is not involved in contraction-stimulated AMPK activation or glucose uptake in adult murine skeletal muscle: a selective CaMKK2 inhibitor (SGC-CAMKK2-1) and CaMKK2 KO mice show no impairment in contraction-stimulated AMPK phosphorylation or glucose uptake. CaMKK2 protein is undetectable in adult murine skeletal muscle by immunoblot or mass spectrometry. SGC-CAMKK2-1 selective inhibitor, CaMKK2 KO mice, ex vivo contraction assays, AMPK activity assays, proteomics, mass spectrometry Molecular metabolism High 37380024
2015 Using STO-609-resistant CaMKK isoform mutants in living cells, CaMKKβ (CAMKK2) was established as the isoform responsible for ionomycin-induced AMPK phosphorylation at Thr172, whereas both CaMKKα and CaMKKβ are capable of phosphorylating and activating CaMKIV at Thr196. STO-609-resistant CaMKK mutant cell lines (Ala328Thr/Val269Phe for CaMKKβ), ionomycin stimulation, AMPK and CaMKIV phosphorylation assays in living cells Biochemistry High 26050738
2009 Exendin-4 stimulates glucokinase gene transcription in pancreatic β-cells via the CaMKK/CaMKIV cascade: STO-609 (CaMKK inhibitor) abolishes exendin-4-induced GK promoter activity and GK protein upregulation; constitutively active CaMKIV enhances GK promoter activity. Reporter gene assay for GK promoter, STO-609 inhibition, CaMKIV phosphorylation assays, constitutively active CaMKIV expression, INS-1 cells Diabetes, obesity & metabolism Medium 19486109

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell metabolism 314 18460329
2013 The CAMKK2-AMPK kinase pathway mediates the synaptotoxic effects of Aβ oligomers through Tau phosphorylation. Neuron 299 23583109
2017 The PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer. Molecular cell 269 29249655
2016 The Ca(2+)/Calmodulin/CaMKK2 Axis: Nature's Metabolic CaMshaft. Trends in endocrinology and metabolism: TEM 179 27449752
2007 Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. American journal of physiology. Endocrinology and metabolism 177 17213473
2012 Withdrawal of essential amino acids increases autophagy by a pathway involving Ca2+/calmodulin-dependent kinase kinase-β (CaMKK-β). The Journal of biological chemistry 104 23027865
2015 The camKK2/camKIV relay is an essential regulator of hepatic cancer. Hepatology (Baltimore, Md.) 97 25847065
2021 Macropinocytosis in Cancer-Associated Fibroblasts Is Dependent on CaMKK2/ARHGEF2 Signaling and Functions to Support Tumor and Stromal Cell Fitness. Cancer discovery 96 33653692
2017 Akt activation by Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in ovarian cancer cells. The Journal of biological chemistry 94 28634229
2022 Aβ42 oligomers trigger synaptic loss through CAMKK2-AMPK-dependent effectors coordinating mitochondrial fission and mitophagy. Nature communications 92 35915085
2019 CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer. Nature communications 85 31164648
2009 CaMKK is an upstream signal of AMP-activated protein kinase in regulation of substrate metabolism in contracting skeletal muscle. American journal of physiology. Regulatory, integrative and comparative physiology 84 19812359
2009 BDNF-mediated cerebellar granule cell development is impaired in mice null for CaMKK2 or CaMKIV. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 19605628
2018 Chemerin suppresses neuroinflammation and improves neurological recovery via CaMKK2/AMPK/Nrf2 pathway after germinal matrix hemorrhage in neonatal rats. Brain, behavior, and immunity 76 29499303
2016 Hypoxia upregulates Malat1 expression through a CaMKK/AMPK/HIF-1α axis. International journal of oncology 76 27499160
2011 The Ca2+/calmodulin-dependent protein kinase kinase, CaMKK2, inhibits preadipocyte differentiation. Endocrinology 76 21862616
2021 NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer. Cancer letters 70 34229059
2007 Association of polymorphisms in P2RX7 and CaMKKb with anxiety disorders. Journal of affective disorders 70 17197037
2016 AMPK Causes Cell Cycle Arrest in LKB1-Deficient Cells via Activation of CAMKK2. Molecular cancer research : MCR 67 27141100
2011 Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes. Journal of cellular biochemistry 67 21312243
2021 CAMKK2 Defines Ferroptosis Sensitivity of Melanoma Cells by Regulating AMPK‒NRF2 Pathway. The Journal of investigative dermatology 65 34242660
2012 A regulatory feedback loop between Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and the androgen receptor in prostate cancer progression. The Journal of biological chemistry 64 22654108
2009 Schizosaccharomyces pombe cell division cycle under limited glucose requires Ssp1 kinase, the putative CaMKK, and Sds23, a PP2A-related phosphatase inhibitor. Genes to cells : devoted to molecular & cellular mechanisms 63 19371376
2016 Store-operated calcium entry-activated autophagy protects EPC proliferation via the CAMKK2-MTOR pathway in ox-LDL exposure. Autophagy 62 27791458
2023 Cdo1-Camkk2-AMPK axis confers the protective effects of exercise against NAFLD in mice. Nature communications 59 38110408
2015 Autocrine Activation of CHRM3 Promotes Prostate Cancer Growth and Castration Resistance via CaM/CaMKK-Mediated Phosphorylation of Akt. Clinical cancer research : an official journal of the American Association for Cancer Research 59 26071486
2018 GLUT12 promotes prostate cancer cell growth and is regulated by androgens and CaMKK2 signaling. Endocrine-related cancer 57 29431615
2012 Deletion of CaMKK2 from the liver lowers blood glucose and improves whole-body glucose tolerance in the mouse. Molecular endocrinology (Baltimore, Md.) 57 22240810
2018 CAMKK2 Promotes Prostate Cancer Independently of AMPK via Increased Lipogenesis. Cancer research 56 30242113
2014 Mechanisms of expression and translocation of major fission yeast glucose transporters regulated by CaMKK/phosphatases, nuclear shuttling, and TOR. Molecular biology of the cell 56 25411338
2019 Chemerin reverses neurological impairments and ameliorates neuronal apoptosis through ChemR23/CAMKK2/AMPK pathway in neonatal hypoxic-ischemic encephalopathy. Cell death & disease 55 30718467
2017 Genotoxic Damage Activates the AMPK-α1 Isoform in the Nucleus via Ca2+/CaMKK2 Signaling to Enhance Tumor Cell Survival. Molecular cancer research : MCR 54 29133590
2008 Oxytocin stimulates glucose uptake in skeletal muscle cells through the calcium-CaMKK-AMPK pathway. Regulatory peptides 54 18555543
2021 Salvianolic Acid C Protects against Cisplatin-Induced Acute Kidney Injury through Attenuation of Inflammation, Oxidative Stress and Apoptotic Effects and Activation of the CaMKK-AMPK-Sirt1-Associated Signaling Pathway in Mouse Models. Antioxidants (Basel, Switzerland) 51 34679755
2020 A complete map of the Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) signaling pathway. Journal of cell communication and signaling 51 33136287
2016 uPA Attenuated LPS-induced Inflammatory Osteoclastogenesis through the Plasmin/PAR-1/Ca(2+)/CaMKK/AMPK Axis. International journal of biological sciences 51 26722218
2019 Fibroblast growth factor 21 Ameliorates diabetes-induced endothelial dysfunction in mouse aorta via activation of the CaMKK2/AMPKα signaling pathway. Cell death & disease 50 31511499
2021 Inhibition of CAMKK2 impairs autophagy and castration-resistant prostate cancer via suppression of AMPK-ULK1 signaling. Oncogene 49 33531625
2017 Pharmacological inhibition of CaMKK2 with the selective antagonist STO-609 regresses NAFLD. Scientific reports 44 28924233
2013 Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene. Molecular psychiatry 44 23958956
2008 Bradykinin stimulates endothelial cell fatty acid oxidation by CaMKK-dependent activation of AMPK. Atherosclerosis 44 18191860
2012 Methyl cinnamate inhibits adipocyte differentiation via activation of the CaMKK2-AMPK pathway in 3T3-L1 preadipocytes. Journal of agricultural and food chemistry 43 22273148
2010 The M3-muscarinic acetylcholine receptor stimulates glucose uptake in L6 skeletal muscle cells by a CaMKK-AMPK-dependent mechanism. Cellular signalling 42 20206685
2019 Progranulin alleviates podocyte injury via regulating CAMKK/AMPK-mediated autophagy under diabetic conditions. Journal of molecular medicine (Berlin, Germany) 38 31402399
2024 Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer. Journal of advanced research 37 38724006
2018 Piperine Promotes Glucose Uptake through ROS-Dependent Activation of the CAMKK/AMPK Signaling Pathway in Skeletal Muscle. Molecular nutrition & food research 37 29683271
2023 Evaluation of lung protection of Sanghuangporus sanghuang through TLR4/NF-κB/MAPK, keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-β/SMAD3 signaling pathways mediating apoptosis and autophagy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 37392658
2022 A molecular complex of Cav1.2/CaMKK2/CaMK1a in caveolae is responsible for vascular remodeling via excitation-transcription coupling. Proceedings of the National Academy of Sciences of the United States of America 34 35412911
2020 CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins. The Journal of biological chemistry 34 32913128
2018 CaMKK2 Regulates Mechanosensitive Assembly of Contractile Actin Stress Fibers. Cell reports 33 29972773
2018 Inhibition of calcium/calmodulin-dependent protein kinase kinase (CaMKK) exacerbates impairment of endothelial cell and blood-brain barrier after stroke. The European journal of neuroscience 33 30422362
2018 Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32 29314250
2018 14-3-3 protein directly interacts with the kinase domain of calcium/calmodulin-dependent protein kinase kinase (CaMKK2). Biochimica et biophysica acta. General subjects 32 29649512
2022 Empagliflozin-Enhanced Antioxidant Defense Attenuates Lipotoxicity and Protects Hepatocytes by Promoting FoxO3a- and Nrf2-Mediated Nuclear Translocation via the CAMKK2/AMPK Pathway. Antioxidants (Basel, Switzerland) 31 35624663
2011 Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation. RNA biology 31 21957496
2021 Dihydromyricetin Ameliorates Inflammation-Induced Insulin Resistance via Phospholipase C-CaMKK-AMPK Signal Pathway. Oxidative medicine and cellular longevity 30 34650665
2020 In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds. Molecules (Basel, Switzerland) 30 31941153
2022 Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma. Nature communications 29 36309495
2016 Calcitriol Reduces Hepatic Triglyceride Accumulation and Glucose Output Through Ca2+/CaMKKβ/AMPK Activation Under Insulin-Resistant Conditions in Type 2 Diabetes Mellitus. Current molecular medicine 29 27658467
2015 Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder. Scientific reports 29 26395653
2023 Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway. Chinese journal of natural medicines 28 37245875
2023 Bufalin targeting CAMKK2 inhibits the occurrence and development of intrahepatic cholangiocarcinoma through Wnt/β-catenin signal pathway. Journal of translational medicine 28 38082327
2022 Regulation and role of CAMKK2 in prostate cancer. Nature reviews. Urology 28 35474107
2009 Exendin-4 regulates glucokinase expression by CaMKK/CaMKIV pathway in pancreatic beta-cell line. Diabetes, obesity & metabolism 28 19486109
2021 Activation of transient receptor potential vanilloid 4 protects articular cartilage against inflammatory responses via CaMKK/AMPK/NF-κB signaling pathway. Scientific reports 27 34330980
2014 The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats. Toxicology 27 25089838
2016 Facilitation of axon outgrowth via a Wnt5a-CaMKK-CaMKIα pathway during neuronal polarization. Molecular brain 26 26772170
2016 Research Resource: Roles for Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) in Systems Metabolism. Molecular endocrinology (Baltimore, Md.) 26 27003444
2014 Genetic deletion of calcium/calmodulin-dependent protein kinase kinase β (CaMKK β) or CaMK IV exacerbates stroke outcomes in ovariectomized (OVXed) female mice. BMC neuroscience 26 25331941
2025 Orchestrating Intracellular Calcium Signaling Cascades by Phosphosite-Centric Regulatory Network: A Comprehensive Analysis on Kinases CAMKK1 and CAMKK2. Omics : a journal of integrative biology 25 40079160
2021 Molecular Profiling Associated with Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2)-Mediated Carcinogenesis in Gastric Cancer. Journal of proteome research 25 33844560
2020 The Histone Demethylase JMJD1C Regulates CAMKK2-AMPK Signaling to Participate in Cardiac Hypertrophy. Frontiers in physiology 25 32625104
2021 Theaflavin Promotes Mitochondrial Abundance and Glucose Absorption in Myotubes by Activating the CaMKK2-AMPK Signal Axis via Calcium-Ion Influx. Journal of agricultural and food chemistry 24 34260232
2021 Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes. Journal of medicinal chemistry 24 34264658
2016 CaMKK2 Suppresses Muscle Regeneration through the Inhibition of Myoblast Proliferation and Differentiation. International journal of molecular sciences 24 27783047
2024 CaMKK2: bridging the gap between Ca2+ signaling and energy-sensing. Essays in biochemistry 23 39268917
2021 Dihydromyricetin resists inflammation-induced muscle atrophy via ryanodine receptor-CaMKK-AMPK signal pathway. Journal of cellular and molecular medicine 23 34676967
2018 Androgen Receptor-CaMKK2 Axis in Prostate Cancer and Bone Microenvironment. Frontiers in endocrinology 23 29967592
2011 A cell-intrinsic role for CaMKK2 in granulocyte lineage commitment and differentiation. Journal of leukocyte biology 23 21816924
2020 Assembly of Peripheral Actomyosin Bundles in Epithelial Cells Is Dependent on the CaMKK2/AMPK Pathway. Cell reports 22 32209483
2017 Association of low dietary folate intake with lower CAMKK2 gene methylation, adiposity, and insulin resistance in obese subjects. Nutrition research (New York, N.Y.) 22 29540272
2019 CaMKK2 Signaling in Metabolism and Skeletal Disease: a New Axis with Therapeutic Potential. Current osteoporosis reports 21 31115859
2009 Exendin-4 regulates pancreatic ABCA1 transcription via CaMKK/CaMKIV pathway. Journal of cellular and molecular medicine 21 19874424
2020 CAMKK2-CAMK4 signaling regulates transferrin trafficking, turnover, and iron homeostasis. Cell communication and signaling : CCS 20 32460794
2013 CaMKK2: a novel target for shaping the androgen-regulated tumor ecosystem. Trends in molecular medicine 20 23332598
2016 Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients. Journal of neurovirology 19 26785644
2015 Inhibition of CaMKK2 reverses age-associated decline in bone mass. Bone 19 25724145
2023 Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis. Cancer research 18 37335130
2020 Protein ligand interaction analysis against new CaMKK2 inhibitors by use of X-ray crystallography and the fragment molecular orbital (FMO) method. Journal of molecular graphics & modelling 18 32348940
2020 Hypomorphic CAMKK2 in EA.hy926 endothelial cells causes abnormal transferrin trafficking, iron homeostasis and glucose metabolism. Biochimica et biophysica acta. Molecular cell research 18 32485269
2020 BH4 activates CaMKK2 and rescues the cardiomyopathic phenotype in rodent models of diabetes. Life science alliance 17 32699151
2018 An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model. Bioorganic & medicinal chemistry letters 17 29653895
2023 CaMKK2 alleviates myocardial ischemia/reperfusion injury by inhibiting oxidative stress and inflammation via the action on the AMPK-AKT-GSK-3β/Nrf2 signaling cascade. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 16 37338678
2023 CaMKK2 is not involved in contraction-stimulated AMPK activation and glucose uptake in skeletal muscle. Molecular metabolism 16 37380024
2021 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 16 34563205
2021 CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation. Cell death & disease 16 34725334
2021 Oxidative stress induced by hydrogen peroxide promotes glycolysis by activating CaMKK/LKB1/AMPK pathway in broiler breast muscle. Poultry science 16 35063808
2020 Stabilization of Protein-Protein Interactions between CaMKK2 and 14-3-3 by Fusicoccins. ACS chemical biology 16 33146997
2015 Analysis of Distinct Roles of CaMKK Isoforms Using STO-609-Resistant Mutants in Living Cells. Biochemistry 16 26050738
2013 Glyceollin improves endoplasmic reticulum stress-induced insulin resistance through CaMKK-AMPK pathway in L6 myotubes. The Journal of nutritional biochemistry 16 23313043

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