Affinage

STK24

Serine/threonine-protein kinase 24 · UniProt Q9Y6E0

Length
443 aa
Mass
49.3 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STK24 (MST3/Mst3b) is a GCK-III subfamily serine/threonine kinase that integrates apoptotic, neurodevelopmental, and hepatic metabolic signaling through phosphorylation of distinct substrate sets (PMID:9353338, PMID:25456499, PMID:24872548). Its catalytic output depends on autophosphorylation of the activation-loop residue Thr178, with Mn2+ as the preferred cofactor; crystal structures show that Thr178 phosphorylation, coordinated by Arg143/Arg176, drives an activation-loop rotation that switches the kinase to its active conformation (PMID:9353338, PMID:17046825, PMID:20124694). Kinase activity is allosterically amplified ~3-4-fold by the MO25alpha/beta scaffolds, which dock through a defined interface (MO25beta Tyr223 with MST3 Glu58/Ile71) that locks MST3 in a closed, active state, and is held in check by a striatin-anchored PP2A whose disruption causes MST3 hyperphosphorylation (PMID:21423148, PMID:23296203, PMID:21985334). Activation can also proceed non-canonically by dephosphorylation-triggered autophosphorylation at Thr178 and the regulatory-domain site Thr328, the latter licensing MO25 association and release from a basal GM130/GOLGA2 pool (PMID:22229648). During Fas- or staurosporine-induced apoptosis, caspase cleavage at AETD313 removes the C-terminal regulatory domain, activating the catalytic core and driving nuclear translocation via an NLS otherwise opposed by a regulatory-domain NES (PMID:12107159, PMID:15304321). As an effector kinase, MST3 phosphorylates NDR1/2 at their hydrophobic motif (Thr442/444) to stimulate NDR activity, TAO1/2 kinases to direct Myosin Va-dependent dendritic spine and synapse development, RhoA at Ser26 to suppress its GTPase activity and control radial neuronal migration downstream of Cdk5-mediated Ser79 phosphorylation, and PTP-PEST to modulate paxillin phosphorylation and inhibit cell migration (PMID:16314523, PMID:25456499, PMID:24872548, PMID:17046825). Through a proline-rich motif engaging the VAV2 SH3 domain, MST3 activates VAV2-Rac1 signaling to promote breast cancer proliferation and tumorigenicity (PMID:26910843). The brain-restricted Mst3b isoform, distinguished by a PKA site at Thr18, mediates trophic-factor- and purine-dependent axon regeneration in CNS and PNS neurons (PMID:10644707, PMID:19855390, PMID:17114295). MST3 also coats hepatic lipid droplets, where it promotes lipogenesis and acetyl-CoA carboxylase abundance while suppressing fatty acid oxidation, and its loss in mice protects against insulin resistance and NAFLD (PMID:31173506, PMID:28956081, PMID:33891332).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1997 High

    Established STK24 as an autoactivating serine/threonine kinase, defining the basic enzymatic identity and its unusual Mn2+ and GTP/ATP usage.

    Evidence In vitro kinase assays on purified recombinant MST3

    PMID:9353338

    Open questions at the time
    • No physiological substrates identified
    • Cellular regulation of autophosphorylation unknown
  2. 2000 High

    Identified a brain-specific MST3b isoform with a unique PKA phosphorylation site (Thr18), revealing isoform-specific regulation and differential MAPK coupling.

    Evidence Northern/Western blots, PKA phosphorylation and T18A mutagenesis in HEK293

    PMID:10644707

    Open questions at the time
    • Functional consequence of Thr18 phosphorylation in neurons not defined
    • Mechanism of differential MAPK activation unclear
  3. 2002 High

    Showed that caspase cleavage at AETD313 removes C-terminal autoinhibition to activate MST3 and drive nuclear translocation during apoptosis, linking the kinase to programmed cell death.

    Evidence Fas/staurosporine treatment, recombinant caspase cleavage, cleavage-site and kinase-dead mutagenesis in Jurkat cells

    PMID:12107159

    Open questions at the time
    • Nuclear substrates of cleaved MST3 not identified
    • Physiological apoptotic contexts beyond cell lines unclear
  4. 2004 Medium

    Mapped the NLS and NES governing MST3 shuttling, explaining how regulatory-domain signals control nuclear access.

    Evidence EGFP-fusion deletions and leptomycin B in fluorescence microscopy

    PMID:15304321

    Open questions at the time
    • Signals controlling shuttling in physiological conditions not defined
    • Single-lab localization study without endogenous validation
  5. 2005 High

    Identified NDR1/2 as direct MST3 substrates at their hydrophobic motif, placing MST3 upstream of NDR kinase activation.

    Evidence In vitro kinase assay, shRNA knockdown and dominant-negative MST3 with phospho-specific antibodies in HEK293F

    PMID:16314523

    Open questions at the time
    • Downstream NDR-dependent outputs in this context not defined
    • Conditions selecting NDR among substrates unknown
  6. 2006 High

    Defined Thr178 autophosphorylation as essential for activity and showed MST3 suppresses migration via PTP-PEST/paxillin, establishing a cytoskeletal-regulatory role.

    Evidence siRNA/rescue, T178A mutagenesis, PTP-PEST phosphatase and paxillin phospho-assays in MCF-7

    PMID:17046825

    Open questions at the time
    • Direct PTP-PEST phosphosite not mapped
    • Relationship between migration suppression and later oncogenic role unresolved
  7. 2006 High

    Linked Mst3b activity to purine- and trophic-factor-driven axon outgrowth, with direct small-molecule modulation by inosine and 6-thioguanine.

    Evidence In vitro kinase assays with purines, siRNA/dominant-negative in cortical neuron outgrowth assays

    PMID:17114295

    Open questions at the time
    • Direct purine-binding mechanism not established
    • Substrates mediating axon outgrowth not identified
  8. 2008 Medium

    Implicated MST3 in oxidative-stress-induced trophoblast apoptosis downstream of JNK and upstream of caspase-3.

    Evidence shRNA, kinase-dead overexpression, JNK/caspase inhibitor epistasis in trophoblast cells

    PMID:18040775

    Open questions at the time
    • Direct MST3 substrates in this pathway unknown
    • Single cell-line model
  9. 2009 High

    Demonstrated Mst3b is required for trophic-factor-induced axon regeneration in vivo, validating its neuronal regenerative function.

    Evidence shRNA, kinase-dead/constitutively-active mutants, optic nerve crush and DRG regeneration with MAPK readout

    PMID:19855390

    Open questions at the time
    • Direct substrates coupling Mst3b to MAPK not defined
    • Translational applicability to other injury models unclear
  10. 2009 Medium

    Showed MST3 drives a caspase-independent apoptotic arm via mitochondrial AIF/EndoG release, broadening its death-signaling repertoire.

    Evidence Stable shRNA, JC-1 membrane potential, AIF/EndoG translocation and nuclease assays

    PMID:19782762

    Open questions at the time
    • Direct MST3 substrates upstream of mitochondrial events unknown
    • Relationship to caspase-cleavage pathway not reconciled
  11. 2010 High

    Resolved crystal structures defining Mn2+ coordination and the activation-loop rotation triggered by Thr178 phosphorylation, providing the structural basis of activation.

    Evidence X-ray crystallography of MST3 catalytic domain with ADP/Mn2+ and adenine

    PMID:20124694

    Open questions at the time
    • Full-length regulatory-domain structure absent
    • Conformational dynamics in cells not captured
  12. 2010 Low

    Reported LRRK2 as an in vitro kinase for STK24, raising a possible upstream regulatory link.

    Evidence Protein microarray screen and in vitro kinase assay

    PMID:20949042

    Open questions at the time
    • Single microarray without reciprocal validation or mutagenesis
    • Phosphosite and cellular relevance unestablished
  13. 2011 High

    Identified MO25alpha/beta as allosteric activators of MST3, establishing scaffold-driven control of kinase output.

    Evidence Reciprocal co-IP, in vitro kinase assay, siRNA/rescue

    PMID:21423148

    Open questions at the time
    • Stoichiometry and dynamics in cells not defined
    • Substrate selection by MO25-bound MST3 unclear
  14. 2011 High

    Defined striatin-scaffolded PP2A as a negative regulator dephosphorylating MST3, completing an activator/inhibitor balance.

    Evidence Co-IP, point/deletion mutagenesis mapping with phosphorylation readouts

    PMID:21985334

    Open questions at the time
    • Quantitative interplay with MO25 activation not resolved
    • In vivo relevance of the striatin-PP2A axis unknown
  15. 2012 High

    Revealed a dephosphorylation-triggered, two-site autophosphorylation mechanism (Thr178/Thr328) coupling release from GM130 to MO25 binding.

    Evidence Co-IP, calyculin A, site-directed mutagenesis, in vitro kinase assays

    PMID:22229648

    Open questions at the time
    • Physiological trigger for the dephosphorylation step unknown
    • Functional consequence of GM130 sequestration undefined
  16. 2013 High

    Solved the MST3-MO25beta complex structure and validated interface residues required for allosteric activation.

    Evidence X-ray crystallography with Y223/E58/I71 mutagenesis and kinase assays

    PMID:23296203

    Open questions at the time
    • Whether MO25 alters substrate specificity not addressed
    • Dynamics of complex assembly in cells unknown
  17. 2014 High

    Used chemical-genetic substrate trapping to identify TAO1/2 as MST3 substrates governing Myosin Va-dependent spine and synapse development.

    Evidence Analog-sensitive kinase, SILAC substrate ID, in utero electroporation, shRNA/kinase-dead

    PMID:25456499

    Open questions at the time
    • Roles of the other identified substrates unexplored
    • TAO phosphosites linking to Myosin Va not fully mapped
  18. 2014 High

    Showed MST3 controls radial neuronal migration by phosphorylating RhoA at Ser26 downstream of Cdk5 Ser79 phosphorylation, with RhoA epistasis rescuing the phenotype.

    Evidence In utero electroporation, in vitro kinase/mutagenesis, RhoA-GTP pulldown, genetic rescue

    PMID:24872548

    Open questions at the time
    • How Cdk5 input integrates with MO25/striatin regulation unclear
    • Other GTPase substrates not surveyed
  19. 2016 High

    Established an oncogenic MST3-VAV2-Rac1 axis through a proline-rich motif/SH3 interaction promoting breast cancer growth.

    Evidence Co-IP, domain mapping, GTP-Rac1 pulldown, soft agar and xenograft assays

    PMID:26910843

    Open questions at the time
    • Reconciliation with MST3's migration-suppressive role unresolved
    • Whether catalytic activity vs scaffolding drives the effect unclear
  20. 2016 Medium

    Defined catalytic-cleft determinants of phosphosite specificity, showing site preference dictates distinct signaling outputs across the kinase family.

    Evidence Peptide arrays, structure-guided mutagenesis, cell-based signaling assays

    PMID:30897078

    Open questions at the time
    • MST3-specific consensus not exhaustively validated
    • Part of a broader STE20 family study
  21. 2017 High

    Identified MST3 as a suppressor of insulin signaling, with knockout mice protected from diet-induced insulin resistance, linking the kinase to metabolic disease.

    Evidence Mst3 knockout HFD mice, RNAi in human liver cells, insulin pathway immunoblotting

    PMID:28956081

    Open questions at the time
    • Direct MST3 substrates in the insulin pathway not identified
    • Tissue-specific contributions undefined
  22. 2019 High

    Localized MST3 to hepatic lipid droplets and showed it promotes lipogenesis while inhibiting beta-oxidation, defining a hepatic metabolic function.

    Evidence siRNA in human hepatocytes, lipid droplet imaging, beta-oxidation/secretion/uptake assays, gene expression

    PMID:31173506

    Open questions at the time
    • Mechanism targeting MST3 to lipid droplets unknown
    • Kinase substrates controlling lipogenic genes not identified
  23. 2021 High

    Demonstrated therapeutic potential by showing ASO silencing of Mst3 ameliorates NAFLD in obese mice.

    Evidence ASO treatment in HFD mice, liver histology, ACC immunoblotting, stress markers

    PMID:33891332

    Open questions at the time
    • Long-term safety and specificity of MST3 inhibition unknown
    • Direct molecular targets driving steatosis reduction undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying logic that selects which substrate set (apoptotic, neuronal, metabolic, oncogenic) MST3 acts on in a given cell remains unresolved, as does how scaffold (MO25/striatin), localization (GM130/lipid droplet), and upstream kinase inputs (Cdk5/PKA) are integrated.
  • No integrated model linking regulatory inputs to substrate choice
  • Mechanism of lipid-droplet targeting unknown
  • Reconciliation of pro-apoptotic, pro-migratory-suppressive, and oncogenic roles missing

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005794 Golgi apparatus 1 GO:0005811 lipid droplet 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 2
Partners
GOLGA2MO25 (CAB39)NDR1/NDR2 (STK38)PTPN12 (PTP-PEST)RHOASTRN (STRIATIN)TAOK1/TAOK2VAV2
Complex memberships
striatin-PP2A complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 MST3 (mst-3) was cloned and characterized as a serine/threonine kinase that phosphorylates basic exogenous substrates and itself in vitro, preferring Mn2+ over Mg2+ as a divalent cation cofactor and able to use both GTP and ATP as phosphate donors; activation occurs by autophosphorylation. In vitro kinase assay, biochemical characterization of purified recombinant protein The Journal of biological chemistry High 9353338
2000 A brain-specific isoform of MST3, termed MST3b (encoded by STK24), was identified with expression restricted to brain. MST3b is phosphorylated by cAMP-dependent protein kinase (PKA) at Thr-18, a site absent in MST3, and mutation T18A abolishes PKA phosphorylation and partially activates p42/44 MAPK, whereas MST3 (but not MST3b) activates p42/44 MAPK up to 4-fold. Northern blot, Western blot, in vivo and in vitro PKA phosphorylation assay, site-directed mutagenesis (T18A), co-transfection in HEK293 cells The Journal of biological chemistry High 10644707
2002 MST3 (Mst3) is specifically cleaved by caspase (at AETD313) during Fas- or staurosporine-induced apoptosis in Jurkat cells. Caspase-mediated removal of the C-terminal regulatory domain activates intrinsic kinase activity and promotes nuclear translocation. Kinase activity is required for apoptotic effects; catalytically inactive Mst3 does not induce DNA fragmentation. Anti-Fas antibody and staurosporine treatment of Jurkat cells, caspase inhibitor (Ac-DEVD-CHO), recombinant caspase assay, site-directed mutagenesis of cleavage site, overexpression of WT vs. kinase-dead Mst3, TUNEL/morphology assays The Journal of biological chemistry High 12107159
2004 MST3 (Mst3) contains a bipartite-like nuclear localization sequence (NLS) at residues 278–292 (C-terminus of kinase domain) and nuclear export signals in the regulatory domain (residues 335–386). Removal of the NLS leads to cytoplasmic accumulation, while deletion of NES or leptomycin B treatment leads to nuclear accumulation. EGFP-fusion protein serial deletions, leptomycin B treatment, fluorescence microscopy FEBS letters Medium 15304321
2005 MST3 phosphorylates NDR1/NDR2 protein kinase at the hydrophobic motif site Thr444/Thr442 in vitro, resulting in ~10-fold stimulation of NDR activity. In vivo, kinase-dead MST3 (MST3KR) potently inhibits Thr442 phosphorylation after okadaic acid stimulation, and shRNA knockdown of MST3 abolishes hydrophobic motif phosphorylation of NDR in HEK293F cells. In vitro kinase assay, shRNA knockdown, dominant-negative (MST3KR) overexpression, phospho-specific antibody detection in HEK293F cells Molecular and cellular biology High 16314523
2006 MST3 inhibits cell migration in MCF-7 cells; siRNA suppression of MST3 enhances migration and reduces E-cadherin at migrating cell edges. Autophosphorylation at Thr178 is required for kinase activity; T178A mutant lacks autophosphorylation and kinase activity and fails to inhibit migration. MST3 phosphorylates PTP-PEST and inhibits its tyrosine phosphatase activity, thereby modulating paxillin phosphorylation at Y118 and Y31. siRNA knockdown, RNAi-resistant rescue, in vitro kinase assay, site-directed mutagenesis (T178A), paxillin phospho-specific antibodies, PTP-PEST phosphatase activity assay The Journal of biological chemistry High 17046825
2009 Mst3b (encoded by Stk24) mediates axon-promoting effects of trophic factors in retinal ganglion cells (RGCs) and dorsal root ganglion (DRG) neurons. shRNA knockdown of Mst3b prevents trophic-factor-induced axon regeneration; kinase-dead Mst3b blocks axon extension; constitutively active Mst3b enables axon growth without growth factors. In vivo, Mst3b-deficient RGCs fail to regenerate axons after optic nerve crush with intraocular inflammation, and Mst3b knockdown attenuates DRG axon regeneration and p42/44 MAPK activation. shRNA knockdown, kinase-dead and constitutively active mutant expression, in vitro neurite outgrowth assay, in vivo optic nerve crush model, p42/44 MAPK immunoblotting Nature neuroscience High 19855390
2006 Mst3b (STK24 isoform) is activated in response to trophic factors and by the purine nucleoside inosine (an axon growth promoter), while 6-thioguanine (a purine analog that blocks axon outgrowth) inhibits Mst3b kinase activity. siRNA suppression or dominant-negative expression of Mst3b blocks axon outgrowth in embryonic cortical neurons. In vitro kinase assay with inosine/6-thioguanine, siRNA knockdown, dominant-negative mutant expression, neurite outgrowth assay Proceedings of the National Academy of Sciences of the United States of America High 17114295
2010 Crystal structures of human MST3 catalytic domain (residues 19–289) were solved in complexes with ADP and Mn2+, and with adenine alone. The structures show that Mn2+ is coordinated by Asn149 and Asp162, and that phosphorylation of Thr178 in the activation loop (sandwiched by Arg143 and Arg176) is associated with a 180° loop rotation leading to kinase activation. X-ray crystallography (multiple crystal structures) Acta crystallographica. Section D, Biological crystallography High 20124694
2011 MO25α and MO25β bind to MST3 (and MST4/YSK1) and stimulate MST3 kinase activity ~3–4-fold. siRNA-mediated reduction of MO25 in cells inhibits downstream signaling, rescued by re-expression of MO25α. Co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, rescue experiment The EMBO journal High 21423148
2011 Striatin scaffolds MST3 and recruits PP2A to regulate MST3 phosphorylation and activity. PP2A binds the coiled-coil/oligomerization domain of striatin (requiring its caveolin-binding domain for oligomerization), while MST3 associates with striatin residues 191–344 likely as a dimer with CCM3. Point mutations in striatin that disrupt PP2A binding cause hyperphosphorylation and activation of striatin-associated MST3 via autophosphorylation of multiple activation loop sites. Co-immunoprecipitation, point mutagenesis, structure-function deletion analysis, phosphorylation state analysis BMC biochemistry High 21985334
2012 A non-canonical pathway of MST3 activation involves dephosphorylation: inactive MST3 co-immunoprecipitates with Golgi protein GOLGA2/GM130 in basal state. Phosphatase inhibition (calyculin A) triggers autophosphorylation of MST3 at both Thr178 (activation loop, increases kinase activity) and Thr328 (regulatory domain, requires residues 341–376 as a docking domain). Thr328 phosphorylation is necessary for MST3 to associate with MO25 and for MST3 dissociation from GM130. Co-immunoprecipitation, calyculin A treatment, site-directed mutagenesis, in vitro kinase assay, phospho-specific antibodies The Biochemical journal High 22229648
2013 Crystal structure of MST3 catalytic domain (residues 19–289) in complex with full-length MO25β reveals an intricate interface stabilizing MST3 in a closed, active conformation. Interface residues Tyr223 of MO25β and Glu58 and Ile71 of MST3, when mutated, prevent MST3 activation by MO25β. The MO25β binding mode is analogous to MO25α interaction with pseudokinase STRADα. X-ray crystallography, site-directed mutagenesis (Y223, E58, I71), in vitro kinase activity assay Biochemical and biophysical research communications High 23296203
2014 MST3 kinase activity is essential for dendritic filopodia, spine synapse, and excitatory synapse development in hippocampal neurons. Chemical-genetic substrate trapping identified 13 MST3 substrates; TAO1/2 kinases were validated substrates whose phosphorylation by MST3 is required for Myosin Va dendritic localization and spine development. shRNA knockdown, kinase-dead MST3 expression, in utero electroporation (spine density in vivo), chemical genetics (analog-sensitive kinase), SILAC-based substrate identification, phospho-site mapping Neuron High 25456499
2014 MST3 regulates radial neuronal migration in the developing neocortex. Mst3 silencing (in utero electroporation) perturbs multipolar-to-bipolar transition of migrating neurons. Kinase activity of MST3 is required for this function and is regulated by Cdk5 phosphorylation of MST3 at Ser79. MST3 phosphorylates RhoA at Ser26, thereby negatively regulating RhoA GTPase activity; RhoA knockdown rescues migration defects caused by Mst3 knockdown. In utero electroporation (shRNA), in vitro kinase assay, Cdk5 phosphorylation assay (Ser79 mutagenesis), RhoA-GTP pulldown assay, rescue epistasis (RhoA knockdown) The Journal of neuroscience High 24872548
2016 MST3 promotes proliferation and tumorigenicity in breast cancer through interaction with VAV2 via a proline-rich region (353KDIPKRP359) of MST3 binding the SH3 domain of VAV2. This interaction leads to VAV2 phosphorylation and Rac1 (GTP-Rac1) activation, cyclin D1 expression, and increased cell growth; mutation of the proline-rich domain (ΔP-MST3) abolishes VAV2 interaction and oncogenic effects. Co-immunoprecipitation, confocal microscopy co-localization, domain mapping mutagenesis, GTP-Rac1 pulldown assay, shRNA knockdown, soft agar growth assay, xenograft tumor formation Oncotarget High 26910843
2017 MST3/STK24 inhibits the insulin signaling pathway: MST3 knockout mice on a high-fat diet show reduced hyperglycemia, hyperinsulinemia, and insulin resistance. Lack of MST3 activates insulin signaling downstream of IRS1, increases FOXO1 inhibition, and downregulates gluconeogenic enzyme expression. Mst3 is phosphorylated in livers of mice on an obesity-promoting diet. Mst3 knockout mice (HFD model), RNAi in human liver cells, insulin signaling pathway immunoblotting (phospho-IRS1, Akt, FOXO1), gluconeogenic gene expression analysis Diabetologia High 28956081
2019 MST3 protein coats lipid droplets in mouse and human hepatocytes. MST3 knockdown attenuates lipid accumulation by stimulating β-oxidation and triacylglycerol secretion while inhibiting fatty acid influx and lipid synthesis; mechanistically, lipogenic gene expression and acetyl-CoA carboxylase protein abundance are reduced in MST3-deficient hepatocytes. siRNA knockdown in human hepatocytes, lipid droplet imaging/co-localization, β-oxidation assay, lipid secretion assay, fatty acid uptake assay, gene expression analysis FASEB journal High 31173506
2021 In vivo antisense oligonucleotide (ASO)-mediated silencing of Mst3 in obese mice ameliorates NAFLD (steatosis, inflammation, fibrosis). Mst3 ASOs suppress lipogenic gene expression and ACC protein abundance, and reduce lipotoxicity-mediated oxidative and ER stress in liver. Antisense oligonucleotide treatment in HFD mouse model, liver histology, gene expression analysis, ACC protein immunoblotting, oxidative/ER stress markers FASEB journal High 33891332
2016 Phosphorylation site specificity of MST3/STK24 was defined by peptide arrays; structure-guided mutagenesis identified β3-αC loop residues in the catalytic cleft as specificity determinants. Exchanging key residues between MST4 and PAK4 could largely interconvert their phosphorylation site preferences and downstream signaling (Hippo vs. actin remodeling), demonstrating that catalytic site specificity is necessary and sufficient for distinct signaling outputs. Peptide array (phosphorylation site profiling), structure-guided mutagenesis, cell-based signaling assays (Hippo pathway, actin remodeling readouts) PLoS biology Medium 30897078
2010 STK24 (MST3/STK24) was identified as a novel substrate and interacting protein of LRRK2 kinase by protein microarray. LRRK2 phosphorylates STK24 in vitro. Protein microarray with 260 signal transduction proteins, in vitro kinase assay PloS one Low 20949042
2008 MST3 trophoblast apoptosis: MST3 expression is induced by oxidative stress (H2O2) in human trophoblasts. Overexpression of kinase-dead MST3KR or shRNA knockdown of MST3 suppresses H2O2-induced apoptosis. JNK participates upstream of Mst3 in this pathway, and caspase 3 and downstream apoptotic components are activated by Mst3. shRNA knockdown, kinase-dead (MST3KR) overexpression, JNK inhibitor, caspase inhibitor, apoptosis assays in 3A-sub-E trophoblast cell line Apoptosis Medium 18040775
2009 MST3 triggers a caspase-independent apoptotic pathway: Mst3 knockdown reduces staurosporine-induced apoptosis by ~65%; Mst3 is required for mitochondrial membrane potential transition (Bax regulation), and for nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG), as well as EndoG nuclease activity. Stable shRNA knockdown clones, mitochondrial membrane potential assay (JC-1), AIF/EndoG nuclear translocation by immunofluorescence, nuclease activity assay, caspase inhibitor (z-DEVD-fmk) The international journal of biochemistry & cell biology Medium 19782762

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The Ste20 group kinases as regulators of MAP kinase cascades. Trends in cell biology 536 11316611
2005 The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene 503 15688006
1998 Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. The EMBO journal 331 9545236
1995 Ste20-like protein kinases are required for normal localization of cell growth and for cytokinesis in budding yeast. Genes & development 323 7649470
1996 Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 302 8643578
1996 Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway. Current biology : CB 223 8805275
2003 PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of the Na-K-Cl cotransporter (NKCC1). The Journal of biological chemistry 220 12740379
1995 Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase. Nature 210 7477268
1996 The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain. The Journal of biological chemistry 193 8702870
1995 Cloning and characterization of a human protein kinase with homology to Ste20. The Journal of biological chemistry 176 7665586
2003 MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1. The EMBO journal 165 14517247
2008 SPAK and OSR1: STE20 kinases involved in the regulation of ion homoeostasis and volume control in mammalian cells. The Biochemical journal 163 18092945
1999 A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. The Journal of biological chemistry 153 9890973
2005 Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3. Molecular and cellular biology 140 16314523
1999 A Drosophila TNF-receptor-associated factor (TRAF) binds the ste20 kinase Misshapen and activates Jun kinase. Current biology : CB 133 10021364
1996 Activation of a human Ste20-like kinase by oxidant stress defines a novel stress response pathway. The EMBO journal 131 8887545
2011 MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases. The EMBO journal 122 21423148
2000 SPAK, a STE20/SPS1-related kinase that activates the p38 pathway. Oncogene 122 10980603
1995 Cloning and characterization of a member of the MST subfamily of Ste20-like kinases. Gene 120 8566796
1998 Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase during apoptosis. Oncogene 117 9662336
2008 Biosignaling of mammalian Ste20-related kinases. Cellular signalling 116 18255267
2000 Nck-interacting Ste20 kinase couples Eph receptors to c-Jun N-terminal kinase and integrin activation. Molecular and cellular biology 116 10669731
2012 Molecular physiology of SPAK and OSR1: two Ste20-related protein kinases regulating ion transport. Physiological reviews 115 23073627
2003 The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion. Molecular and cellular biology 107 12612079
2002 Cdc42 regulation of kinase activity and signaling by the yeast p21-activated kinase Ste20. Molecular and cellular biology 98 11940652
1997 Cloning and characterization of a human STE20-like protein kinase with unusual cofactor requirements. The Journal of biological chemistry 95 9353338
2001 MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway. Oncogene 92 11641781
1999 The Drosophila STE20-like kinase misshapen is required downstream of the Frizzled receptor in planar polarity signaling. The EMBO journal 91 10469646
2011 Protein phosphatase 2a (PP2A) binds within the oligomerization domain of striatin and regulates the phosphorylation and activation of the mammalian Ste20-Like kinase Mst3. BMC biochemistry 89 21985334
2009 Happyhour, a Ste20 family kinase, implicates EGFR signaling in ethanol-induced behaviors. Cell 86 19464045
2002 Caspase activation of mammalian sterile 20-like kinase 3 (Mst3). Nuclear translocation and induction of apoptosis. The Journal of biological chemistry 82 12107159
2010 Dcp2 phosphorylation by Ste20 modulates stress granule assembly and mRNA decay in Saccharomyces cerevisiae. The Journal of cell biology 81 20513766
2006 Ste20-type kinases: evolutionarily conserved regulators of ion transport and cell volume. Physiology (Bethesda, Md.) 78 16443823
2007 Evolutionarily conserved WNK and Ste20 kinases are essential for acute volume recovery and survival after hypertonic shrinkage in Caenorhabditis elegans. American journal of physiology. Cell physiology 77 17596296
1999 Induction of apoptosis by SLK, a Ste20-related kinase. Oncogene 77 10602516
2015 Regulation of mammalian Ste20 (Mst) kinases. Trends in biochemical sciences 76 25665457
2000 Ste20-like kinase (SLK), a regulatory kinase for polo-like kinase (Plk) during the G2/M transition in somatic cells. Genes to cells : devoted to molecular & cellular mechanisms 76 10886374
1997 SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1. The Journal of biological chemistry 74 9346925
2009 Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways. Nature neuroscience 73 19855390
2006 Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST. The Journal of biological chemistry 71 17046825
2004 PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans. Molecular biology of the cell 70 15282344
2002 Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST). The Journal of biological chemistry 70 11805089
1997 LOK is a novel mouse STE20-like protein kinase that is expressed predominantly in lymphocytes. The Journal of biological chemistry 69 9278426
2008 Ste20-related kinase SLK phosphorylates Ser188 of RhoA to induce vasodilation in response to angiotensin II Type 2 receptor activation. Circulation research 66 18420945
2014 MST3 kinase phosphorylates TAO1/2 to enable Myosin Va function in promoting spine synapse development. Neuron 65 25456499
2009 The DeMSTification of mammalian Ste20 kinases. Current biology : CB 65 19467213
2001 Cloning and characterization of MST4, a novel Ste20-like kinase. The Journal of biological chemistry 65 11306563
2006 Mst3b, a purine-sensitive Ste20-like protein kinase, regulates axon outgrowth. Proceedings of the National Academy of Sciences of the United States of America 63 17114295
2003 Regulation of mammalian STE20-like kinase 2 (MST2) by protein phosphorylation/dephosphorylation and proteolysis. The Journal of biological chemistry 59 12554736
2009 The Ste20 kinases Ste20-related proline-alanine-rich kinase and oxidative-stress response 1 regulate NKCC1 function in sensory neurons. The Journal of biological chemistry 56 19307180
2006 The STE20/germinal center kinase POD6 interacts with the NDR kinase COT1 and is involved in polar tip extension in Neurospora crassa. Molecular biology of the cell 56 16822837
2014 Cdk5-dependent Mst3 phosphorylation and activity regulate neuronal migration through RhoA inhibition. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 24872548
2011 Smad inhibition by the Ste20 kinase Misshapen. Proceedings of the National Academy of Sciences of the United States of America 50 21690388
2005 The Ste20-like kinase SLK is required for cell cycle progression through G2. The Journal of biological chemistry 48 16236704
1998 Potential regulation of Ste20 function by the Cln1-Cdc28 and Cln2-Cdc28 cyclin-dependent protein kinases. The Journal of biological chemistry 48 9737966
2007 The GCK II and III subfamilies of the STE20 group kinases. Frontiers in bioscience : a journal and virtual library 46 17127342
2011 Ste20-related kinases: effectors of signaling and morphogenesis in fungi. Trends in microbiology 45 21640592
2009 Crystal structure of domain-swapped STE20 OSR1 kinase domain. Protein science : a publication of the Protein Society 45 19177573
2000 The Ste20 kinase misshapen regulates both photoreceptor axon targeting and dorsal closure, acting downstream of distinct signals. Molecular and cellular biology 45 10848599
2014 Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment. Cell death & disease 43 24874741
2007 Proteins involved in sterol synthesis interact with Ste20 and regulate cell polarity. Journal of cell science 43 17895367
2010 Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway. PloS one 42 20231902
2010 Signal transduction protein array analysis links LRRK2 to Ste20 kinases and PKC zeta that modulate neuronal plasticity. PloS one 42 20949042
2000 Identification of a human brain-specific isoform of mammalian STE20-like kinase 3 that is regulated by cAMP-dependent protein kinase. The Journal of biological chemistry 41 10644707
2012 Ste20-like kinase SLK, at the crossroads: a matter of life and death. Cell adhesion & migration 40 23154402
2014 Molecular Screening of Keratoconus Susceptibility Sequence Variants in VSX1, TGFBI, DOCK9, STK24, and IPO5 Genes in Polish Patients and Novel TGFBI Variant Identification. Ophthalmic genetics 39 24940934
2019 Comprehensive profiling of the STE20 kinase family defines features essential for selective substrate targeting and signaling output. PLoS biology 38 30897078
2007 Cdc42 and the Ste20-like kinase Don3 act independently in triggering cytokinesis in Ustilago maydis. Journal of cell science 37 18089648
2001 Androgens induce expression of SPAK, a STE20/SPS1-related kinase, in LNCaP human prostate cancer cells. Molecular and cellular endocrinology 37 11514053
2016 MST3 promotes proliferation and tumorigenicity through the VAV2/Rac1 signal axis in breast cancer. Oncotarget 36 26910843
2009 The Ste20-like kinase SLK is required for ErbB2-driven breast cancer cell motility. Oncogene 36 19525980
2008 Identification of regulatory phosphorylation sites in a cell volume- and Ste20 kinase-dependent ClC anion channel. The Journal of general physiology 35 19088383
2014 The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy. The Journal of biological chemistry 33 25035424
2007 Caenorhabditis elegans WNK-STE20 pathway regulates tube formation by modulating ClC channel activity. EMBO reports 33 18049475
2012 A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3). The Biochemical journal 32 22229648
1998 Characterization and cloning of a Dictyostelium Ste20-like protein kinase that phosphorylates the actin-binding protein severin. The Journal of biological chemistry 32 9582328
2005 Ste20/GCK kinase Nak1/Orb3 polarizes the actin cytoskeleton in fission yeast during the cell cycle. Journal of cell science 31 15731009
2018 Mammalian STE20-Like Kinase 1 Deletion Alleviates Renal Ischaemia-Reperfusion Injury via Modulating Mitophagy and the AMPK-YAP Signalling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 30 30537740
2007 Cloning and characterization of a new intestinal inflammation-associated colonic epithelial Ste20-related protein kinase isoform. Biochimica et biophysica acta 30 17321610
2012 Mammalian ste20-like kinase and SAV1 promote 3T3-L1 adipocyte differentiation by activation of PPARγ. PloS one 29 22292086
2004 Identification and characterization of the nuclear import and export signals of the mammalian Ste20-like protein kinase 3. FEBS letters 28 15304321
2019 Protein kinase MST3 modulates lipid homeostasis in hepatocytes and correlates with nonalcoholic steatohepatitis in humans. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 31173506
2021 Silencing of STE20-type kinase MST3 in mice with antisense oligonucleotide treatment ameliorates diet-induced nonalcoholic fatty liver disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 33891332
2015 Mammalian Ste20-like kinase 4 promotes pituitary cell proliferation and survival under hypoxia. Molecular endocrinology (Baltimore, Md.) 25 25650755
2008 Ste20-related protein kinase LOSK (SLK) controls microtubule radial array in interphase. Molecular biology of the cell 25 18287541
2000 Molecular cloning and characterization of a novel human STE20-like kinase, hSLK. Biochimica et biophysica acta 25 10699464
2017 The MST3/STK24 kinase mediates impaired fasting blood glucose after a high-fat diet. Diabetologia 24 28956081
2016 Discovery of Diverse Small-Molecule Inhibitors of Mammalian Sterile20-like Kinase 3 (MST3). ChemMedChem 24 27135311
2008 Ste20-related proline/alanine-rich kinase: a novel regulator of intestinal inflammation. World journal of gastroenterology 24 18985800
2009 Mammalian Ste20-like protein kinase 3 induces a caspase-independent apoptotic pathway. The international journal of biochemistry & cell biology 23 19782762
2008 Mammalian Ste20-like protein kinase 3 mediates trophoblast apoptosis in spontaneous delivery. Apoptosis : an international journal on programmed cell death 23 18040775
2002 Expression of the Ste20-like kinase SLK during embryonic development and in the murine adult central nervous system. Brain research. Developmental brain research 23 12480135
2020 Cell-substrate adhesion drives Scar/WAVE activation and phosphorylation by a Ste20-family kinase, which controls pseudopod lifetime. PLoS biology 22 32745097
2019 microRNA-222 promotes colorectal cancer cell migration and invasion by targeting MST3. FEBS open bio 22 31034165
2013 Structural insights into the activation of MST3 by MO25. Biochemical and biophysical research communications 22 23296203
2006 v-Src-dependent down-regulation of the Ste20-like kinase SLK by casein kinase II. The Journal of biological chemistry 22 16837460
2011 Activity of the Ste20-like kinase, SLK, is enhanced by homodimerization. American journal of physiology. Renal physiology 21 21677149
2010 Structures of human MST3 kinase in complex with adenine, ADP and Mn2+. Acta crystallographica. Section D, Biological crystallography 21 20124694
2009 The Ste20-like kinase SLK promotes p53 transactivation and apoptosis. American journal of physiology. Renal physiology 21 19640899
2012 GCN-2 dependent inhibition of protein synthesis activates osmosensitive gene transcription via WNK and Ste20 kinase signaling. American journal of physiology. Cell physiology 20 23076791

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