Affinage

STK24

Serine/threonine-protein kinase 24 · UniProt Q9Y6E0

Round 2 corrected
Length
443 aa
Mass
49.3 kDa
Annotated
2026-04-28
130 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STK24 encodes MST3, a GCK-III subfamily Ste20-like serine/threonine kinase that functions as a signaling hub linking upstream regulatory inputs to cytoskeletal remodeling, neuronal development, and hepatic metabolism. MST3 is activated by autophosphorylation of its activation-loop residue Thr178 and by MO25-induced stabilization of the closed kinase conformation, while PP2A within the STRIPAK complex dephosphorylates and inactivates it (PMID:20124694, PMID:23296203, PMID:21985334). Its substrates include NDR kinases (hydrophobic-motif Thr442), RhoA (Ser26, suppressing GTPase activity to enable cortical neuronal migration), TAO1/2 (linking to Myosin Va–dependent dendritic spine formation), and PPP1R14A-D (driving actomyosin contractility and cancer cell migration mode switching) (PMID:16314523, PMID:24872548, PMID:25456499, PMID:25531779). MST3 also localizes to hepatic lipid droplets where it promotes lipid accumulation through ACC-dependent lipogenesis, and its genetic ablation in mice protects against diet-induced NAFLD and insulin resistance (PMID:31173506, PMID:33891332, PMID:28956081).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 Medium

    Early biochemical work placed the GCK-III kinase subfamily containing STK24/MST3 as a selective activator of the p38 MAPK cascade via MKK3, distinguishing it from JNK- and ERK-activating kinases.

    Evidence Co-transfection kinase cascade assays and homodimerization studies in mammalian cells

    PMID:13679851

    Open questions at the time
    • Subfamily-level study; direct assignment to STK24 rests on catalytic domain similarity rather than gene-specific loss-of-function
    • No endogenous substrate identified
  2. 2005 High

    Identification of NDR2 as a direct MST3 substrate established that MST3 functions as an upstream activating kinase for the NDR/LATS family, phosphorylating the hydrophobic motif Thr442 to stimulate NDR activity ~10-fold.

    Evidence In vitro kinase assay with recombinant proteins, kinase-dead mutant, and shRNA knockdown in HEK293F cells

    PMID:16314523

    Open questions at the time
    • Physiological context of MST3→NDR signaling not defined
    • Redundancy with MST4/STK25 not addressed
  3. 2006 High

    The discovery that Mst3b mediates trophic factor– and purine-stimulated axon outgrowth in retinal ganglion cells established the first in vivo neuronal function for MST3, downstream of CNTF, BDNF, and inosine.

    Evidence siRNA knockdown and dominant-negative kinase-dead mutant in RGC axon outgrowth assay

    PMID:17114295

    Open questions at the time
    • Direct phosphorylation substrates in axon growth not identified
    • Relationship to p42/44 MAPK activation unclear
  4. 2008 Medium

    AP-MS identification of STK24 as a core component of STRIPAK provided the physical framework explaining how PP2A-mediated dephosphorylation keeps MST3 inactive in the basal state.

    Evidence Iterative affinity purification–mass spectrometry

    PMID:18782753

    Open questions at the time
    • Functional consequence of STRIPAK membership for MST3 not tested in this study
    • Stoichiometry and dynamics of MST3 within STRIPAK unresolved
  5. 2009 High

    In vivo validation using optic nerve crush and DRG models demonstrated that MST3 kinase activity is required for CNS and PNS axon regeneration, with constitutively active MST3 bypassing the need for trophic factors.

    Evidence shRNA knockdown and constitutively active mutant expression in vivo (optic nerve crush) and in vitro (RGC, DRG cultures)

    PMID:19855390

    Open questions at the time
    • Direct regeneration-relevant substrates remain unknown
    • Therapeutic potential of MST3 activation in axon injury not tested pharmacologically
  6. 2010 High

    Crystal structures of the MST3 catalytic domain revealed that activation-loop autophosphorylation at Thr178 induces a 180° loop rotation anchoring pThr178 between Arg143 and Arg176, providing the structural basis for enzyme activation and Mn²⁺ cofactor preference.

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

    PMID:20124694

    Open questions at the time
    • No substrate-bound structure
    • Mn²⁺ preference not validated in cellular context
  7. 2011 High

    Two complementary studies resolved the dual regulatory logic of MST3: MO25 binds and activates MST3 ~3–4-fold by stabilizing the closed kinase conformation, while within STRIPAK, PP2A dephosphorylates and inactivates MST3, with striatin mutations that disrupt PP2A association causing MST3 hyperactivation.

    Evidence Biochemical binding and kinase assays (MO25), co-IP and mutagenesis of striatin-PP2A interface, okadaic acid treatment

    PMID:21423148 PMID:21985334

    Open questions at the time
    • How cells switch MST3 between STRIPAK-bound (inactive) and MO25-bound (active) states is unclear
    • In vivo phenotypic consequence of disrupting PP2A–MST3 axis not tested
  8. 2012 High

    A non-canonical MST3 activation pathway was delineated: phosphatase inhibition triggers sequential autophosphorylation of Thr178 and then Thr328 in the regulatory domain, with pThr328 required for dissociation from Golgi-resident GM130 and subsequent MO25 binding.

    Evidence Phospho-specific mutant analysis, co-IP with GM130, calyculin A treatment in cells

    PMID:22229648

    Open questions at the time
    • Physiological stimulus that triggers this Golgi-release mechanism not identified
    • Whether pThr328 is a general regulatory mark across cell types is unknown
  9. 2013 High

    The MST3–MO25β co-crystal structure resolved the activation interface at atomic resolution, identifying Tyr223 of MO25β and Glu58/Ile71 of MST3 as essential contact residues, confirming the allosteric activation model.

    Evidence X-ray crystallography of MST3 catalytic domain–MO25β complex with mutagenesis validation

    PMID:23296203

    Open questions at the time
    • Full-length MST3 structure including regulatory domain still unavailable
    • Whether MO25 binding alters substrate selectivity not tested
  10. 2014 High

    Three 2014 studies expanded MST3's substrate repertoire and physiological roles: (1) Cdk5 phosphorylates MST3 at Ser79 to regulate its activity during cortical neuronal migration, where MST3 phosphorylates RhoA at Ser26 to suppress its GTPase activity; (2) chemical-genetic substrate profiling identified TAO1/2 kinases as MST3 substrates that recruit Myosin Va for spine synapse development; (3) within STRIPAK, MST3 phosphorylates PPP1R14A-D to drive actomyosin contractility and determine cancer cell migration mode.

    Evidence In utero electroporation with epistasis rescue (RhoA knockdown); analog-sensitive kinase SILAC proteomics; siRNA of STRIPAK components with in vivo metastasis assays

    PMID:24872548 PMID:25456499 PMID:25531779

    Open questions at the time
    • Whether RhoA-Ser26 phosphorylation is the sole migration-relevant MST3 substrate in neurons is unclear
    • Relative contribution of MST3 versus MST4 in actomyosin regulation not genetically separated
  11. 2016 High

    MST3 was shown to engage VAV2 via its proline-rich motif (353-KDIPKRP-359) binding the VAV2 SH3 domain, promoting Rac1 activation, cyclin D1 expression, and breast cancer cell proliferation—revealing a kinase-independent scaffolding function.

    Evidence Co-IP with proline mutant domain mapping, GTP-Rac1 pull-down, Rac1 inhibitor, in vivo xenograft

    PMID:26910843

    Open questions at the time
    • Whether VAV2 interaction requires MST3 kinase activity is not fully resolved
    • Relevance beyond breast cancer cells not established
  12. 2017 High

    Mst3 knockout mice revealed a metabolic function: MST3 negatively regulates hepatic insulin signaling downstream of IRS1, and its loss protects against diet-induced hyperglycemia and insulin resistance by enhancing inhibitory FOXO1 phosphorylation.

    Evidence Mst3 knockout mouse on high-fat diet, siRNA in human hepatocytes, insulin signaling pathway analysis

    PMID:28956081

    Open questions at the time
    • Direct MST3 phosphorylation target in insulin signaling pathway not identified
    • Whether kinase activity versus scaffolding is required for metabolic phenotype untested
  13. 2019 High

    MST3 was found to localize to hepatic lipid droplets and promote lipid accumulation by sustaining ACC protein levels and lipogenic gene expression; its knockdown diverted metabolism toward β-oxidation and triacylglycerol secretion.

    Evidence siRNA in human hepatocytes, lipid droplet imaging, metabolic flux assays

    PMID:31173506

    Open questions at the time
    • Mechanism of MST3 recruitment to lipid droplets unknown
    • Whether MST3 directly phosphorylates ACC or lipogenic transcription factors not determined
  14. 2021 High

    In vivo ASO-mediated Mst3 knockdown in obese mice confirmed the hepatic lipid-promoting role, ameliorating steatosis, inflammation, and fibrosis, validating MST3 as a potential therapeutic target in NAFLD.

    Evidence ASO knockdown in high-fat diet mice with histology, lipogenic gene expression, and stress marker analysis

    PMID:33891332

    Open questions at the time
    • Long-term safety and off-target effects of Mst3 ASOs not characterized
    • Whether MST3 inhibition is beneficial in non-diet-induced liver disease models untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of direct MST3 substrates in axon regeneration and hepatic insulin signaling, the structural basis for full-length MST3 regulation (including the regulatory C-terminal domain), the mechanism of lipid droplet recruitment, and the extent of functional redundancy with MST4/STK25 across tissues.
  • No full-length MST3 structure available
  • Direct phosphorylation targets in axon regeneration pathway unknown
  • Functional redundancy with MST4 and STK25 not genetically resolved in most contexts

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005794 Golgi apparatus 1 GO:0005811 lipid droplet 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-112316 Neuronal System 3 R-HSA-1430728 Metabolism 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5357801 Programmed Cell Death 1
Complex memberships
STRIPAK

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 MST3 (encoded by STK24) directly phosphorylates NDR2 at the hydrophobic motif site Thr442, causing ~10-fold stimulation of NDR kinase activity in vitro; kinase-dead MST3 (MST3KR) abolished Thr442 phosphorylation in cells, and shRNA knockdown of MST3 eliminated hydrophobic-motif phosphorylation of NDR in HEK293F cells. MOB1A further enhanced NDR activity in this pathway. In vitro kinase assay with recombinant proteins, kinase-dead mutant (MST3KR) overexpression, shRNA knockdown, phospho-specific analysis Molecular and cellular biology High 16314523
2006 Mst3b (the neuron-enriched isoform encoded by Stk24) is activated in response to trophic factors (CNTF, BDNF) and the purine nucleoside inosine, and its kinase activity is inhibited by the purine analog 6-thioguanine. Suppression of Mst3b expression via siRNA or expression of kinase-dead Mst3b blocks axon outgrowth, placing Mst3b as a key downstream mediator of purine- and trophic factor-stimulated axon growth. siRNA knockdown, dominant-negative kinase-dead mutant, in vitro kinase activity assay, axon outgrowth assay in retinal ganglion cells Proceedings of the National Academy of Sciences of the United States of America High 17114295
2009 Mst3b (STK24) mediates the axon-promoting effects of trophic factors in mature rat retinal ganglion cells (RGCs) and dorsal root ganglion (DRG) neurons. shRNA-mediated reduction of Mst3b prevented trophic factor-induced axon regeneration in culture; kinase-dead Mst3b blocked outgrowth; constitutively active Mst3b enabled axon extension without growth factors. In vivo, RGCs lacking Mst3b failed to regenerate after optic nerve injury, and DRG neurons regenerating axons showed elevated Mst3b activity coupled with p42/44 MAPK activation. shRNA knockdown in vivo and in vitro, kinase-dead and constitutively active mutant expression, in vivo optic nerve crush model, in vitro kinase activity assay, p42/44 MAPK phosphorylation readout Nature neuroscience High 19855390
2011 MO25α and MO25β bind to MST3 (STK24) and stimulate its kinase activity approximately 3–4-fold. MO25 binding stabilises the MST3 kinase domain in a closed, active conformation. This interaction is analogous to the way MO25 activates the STRAD pseudokinase, revealing MO25 as a broader regulator of GCK-III and GCK-VI STE20 family kinases. Biochemical binding assays, in vitro kinase activity measurements, siRNA knockdown of MO25 in mammalian cells with rescue by MO25α re-expression The EMBO journal High 21423148
2011 Within the striatin complex, PP2A (recruited through striatin's coiled-coil/oligomerization domain) dephosphorylates and inactivates MST3 (STK24). Point mutations in striatin that disrupt PP2A association cause hyperphosphorylation and activation of striatin-associated MST3. MST3 activation involves autophosphorylation of multiple activation-loop phosphorylation sites; MST3 is recruited to striatin via residues 191–344 likely as a dimer with CCM3. Co-immunoprecipitation, structure-function mutagenesis of striatin, phosphorylation analysis, PP2A inhibitor (okadaic acid) treatment BMC biochemistry High 21985334
2012 An alternative 'non-canonical' activation pathway for MST3 (STK24) involves phosphatase-regulated dephosphorylation rather than caspase cleavage. In the basal state, inactive MST3 co-immunoprecipitates with the Golgi protein GOLGA2/GM130. Calyculin A (PP1/PP2A inhibitor) triggers autophosphorylation of MST3 Thr178 (activation loop) and concurrent cis-autophosphorylation of Thr328 (regulatory domain), the latter requiring MST3 residues 341–376 as a docking domain. Thr328 phosphorylation is necessary for dissociation from GM130 and association with MO25 to form an activated MST3–MO25 complex. Co-immunoprecipitation, pharmacological PP1/PP2A inhibition, phospho-specific mutant analysis, in vitro kinase assay The Biochemical journal High 22229648
2013 Crystal structure of the MST3 catalytic domain (residues 19–289) in complex with full-length MO25β resolved the activation mechanism: MO25β stabilises the MST3 kinase domain in a closed, active conformation. Interface residues Tyr223 of MO25β and Glu58 and Ile71 of MST3 are critical; mutating these residues prevents MO25β from activating MST3. The binding mode resembles MO25α binding to the pseudokinase STRADα. X-ray crystallography, site-directed mutagenesis of interface residues, in vitro kinase activity assay Biochemical and biophysical research communications High 23296203
2014 MST3 (STK24) is required for radial neuronal migration in the developing mouse neocortex. Mst3 silencing by in utero electroporation impaired the multipolar-to-bipolar transition of migrating neurons. MST3 kinase activity (required for its function) is regulated by phosphorylation at Ser79 by Cdk5. MST3 promotes migration by phosphorylating RhoA at Ser26, thereby negatively regulating RhoA GTPase activity; RhoA knockdown rescues the neuronal migration defect caused by Mst3 loss. In utero electroporation with shRNA knockdown and rescue, in vitro kinase assay (Cdk5 phosphorylation of MST3, MST3 phosphorylation of RhoA at Ser26), RhoA GTPase activity assay, epistasis by RhoA knockdown rescue The Journal of neuroscience High 24872548
2014 MST3 (STK24) phosphorylates TAO1 and TAO2 kinases; using chemical genetics (analog-sensitive kinase), 13 MST3 substrates were identified with specific phosphorylation sites. Phosphorylated TAO1/2 associates with Myosin Va, which is necessary for Myosin Va dendritic localization; this MST3–TAO1/2–Myosin Va axis regulates dendritic filopodia, spine, and excitatory synapse development in hippocampal neurons. shRNA knockdown and kinase-dead MST3 expression reduced spine density in vitro and in vivo. Chemical genetics (analog-sensitive kinase), SILAC mass spectrometry, shRNA knockdown in hippocampal cultures and in utero electroporation, kinase-dead mutant, co-immunoprecipitation of TAO1/2 with Myosin Va Neuron High 25456499
2010 Crystal structures of the MST3 catalytic domain were solved in complex with ADP and Mn2+ (at 2.25 Å equivalent) and with adenine, revealing that MST3 preferentially uses Mn2+ as cofactor. The activation loop Thr178 is phosphorylated and its side chain is sandwiched between Arg143 and Arg176, with a 180° loop rotation compared to inactive kinase structures, providing the structural basis for enzyme activation by autophosphorylation. X-ray crystallography of MST3 catalytic domain with ligand complexes Acta crystallographica. Section D, Biological crystallography High 20124694
2008 STK24 (MST3/STK24) was identified as part of the STRIPAK (striatin-interacting phosphatase and kinase) complex by affinity purification–mass spectrometry. STRIPAK contains PP2A catalytic and scaffolding subunits, striatins, Mob3, STRIP1/2, CCM3, and GCK-III kinases including STK24, establishing a physical link between PP2A phosphatase and MST3 within a large signaling assembly. Iterative affinity purification coupled to mass spectrometry (AP-MS) Molecular & cellular proteomics Medium 18782753
2014 Within the STRIPAK complex, FAM40A (STRIP1) negatively regulates MST3 and MST4 kinases, which promote co-localization of contractile actomyosin machinery with ERM proteins by phosphorylating PPP1R14A-D (inhibitors of PPP1CB). This pathway controls the mode of cancer cell migration: high MST3/MST4 activity drives a cortically contractile, confined-environment-favoring migration mode. siRNA knockdown of STRIPAK components, in vitro phosphorylation assays, co-localization studies, computational modelling, in vitro migration assays, in vivo breast cancer metastasis assays Nature cell biology High 25531779
2016 MST3 (STK24) interacts with VAV2 (but not VAV3) via the proline-rich region of MST3 (353KDIPKRP359) binding to the SH3 domain of VAV2. This interaction promotes VAV2 phosphorylation and GTP-Rac1 activation, driving cyclin D1 expression and breast cancer cell proliferation. Mutation of two proline residues in the MST3 proline-rich domain abolishes VAV2 interaction and downstream Rac1 activation. Co-immunoprecipitation, confocal microscopy co-localization, domain mapping with proline mutants, GTP-Rac1 pull-down assay, Rac1 inhibitor (EHop-016), shRNA knockdown, in vivo xenograft Oncotarget High 26910843
2017 MST3 (STK24) is phosphorylated in the livers of mice on a high-fat diet. Mst3 knockout mice are protected from diet-induced hyperglycemia, hyperinsulinemia, and insulin resistance. MST3 deficiency activates the insulin signaling pathway downstream of IRS1, increasing inhibitory phosphorylation of FOXO1 and reducing gluconeogenic enzyme expression, indicating that MST3 negatively regulates hepatic insulin signaling. Mst3 knockout mouse model (129;C57 and C57BL/6J backgrounds), high-fat diet feeding, in vitro siRNA knockdown in human liver cells, insulin signaling pathway analysis (IRS1, AKT phosphorylation), FOXO1 phosphorylation, gluconeogenic gene expression Diabetologia High 28956081
2019 MST3 (STK24) protein coats lipid droplets in mouse and human liver cells. MST3 knockdown in human hepatocytes 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 (ACC) protein abundance are reduced in MST3-deficient hepatocytes. siRNA knockdown in human hepatocytes, lipid droplet co-localization by imaging, metabolic flux assays (β-oxidation, TG secretion), fatty acid influx assay, lipogenic gene expression, ACC protein quantification FASEB journal High 31173506
2021 Antisense oligonucleotide (ASO)-mediated knockdown of Mst3 in obese mice ameliorated NAFLD including liver steatosis, inflammation, fibrosis, and hepatocellular damage. Mechanistically, Mst3 ASOs suppressed lipogenic gene expression and ACC protein abundance, and reduced lipotoxicity-mediated oxidative and ER stress, confirming that MST3 (STK24) promotes hepatic lipid accumulation in vivo. ASO-mediated Mst3 knockdown in high-fat diet mouse model, histological analysis, lipogenic gene expression, ACC protein quantification, oxidative stress and ER stress markers FASEB journal High 33891332
2010 A signal transduction protein array identified STK24 as a novel LRRK2 substrate and interacting protein; four Ste20 kinases (TAOK3, STK3, STK24, STK25) were phosphorylated by LRRK2 in vitro, suggesting that LRRK2 may phosphorylate STK24 in the context of Parkinson's disease-related neuronal signaling. Protein microarray with 260 signal transduction proteins incubated with LRRK2, in vitro phosphorylation assay PloS one Low 20949042
2008 MST3 is essential for oxidative stress-induced apoptosis of human trophoblasts. H2O2 induces MST3 expression and trophoblast apoptosis; overexpression of kinase-dead MST3 (MST3KR) or siRNA knockdown of endogenous MST3 largely suppresses H2O2-induced apoptosis in 3A-sub-E cells. JNK participates upstream to regulate MST3 levels, and caspase 3 acts downstream of MST3 in this pathway. Kinase-dead mutant overexpression, siRNA knockdown, pharmacological inducers of apoptosis, JNK and caspase 3 activity assays Apoptosis Medium 18040775
2003 hKFC (a subfamily of human Ste20-like kinases with >90% catalytic domain similarity, including the member corresponding to STK24/MST3) specifically activates the p38 MAP kinase pathway through selective activation of the upstream kinase MKK3, but does not activate ERK, JNK, or ERK5. Members of this subfamily form homodimers and differ in tissue distribution and subcellular localization despite sharing catalytic specificity. Co-transfection kinase cascade assays, biochemical self-association studies, subcellular localization by microscopy Oncogene Medium 13679851

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2001 The Ste20 group kinases as regulators of MAP kinase cascades. Trends in cell biology 534 11316611
2013 GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. Science (New York, N.Y.) 503 23722424
2005 The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene 499 15688006
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1998 Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. The EMBO journal 331 9545236
1995 A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20. The EMBO journal 327 7744004
2002 Cation chloride cotransporters interact with the stress-related kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1). The Journal of biological chemistry 318 12386165
2003 Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. The EMBO journal 308 12805220
2008 A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein. Molecular & cellular proteomics : MCP 302 18782753
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
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
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
2005 Volume sensitivity of cation-Cl- cotransporters is modulated by the interaction of two kinases: Ste20-related proline-alanine-rich kinase and WNK4. American journal of physiology. Cell physiology 219 15930150
1995 Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase. Nature 210 7477268
2011 A comprehensive genetic association study of Alzheimer disease in African Americans. Archives of neurology 202 22159054
2011 Next-generation sequencing to generate interactome datasets. Nature methods 200 21516116
2007 A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. The Biochemical journal 194 17253963
1998 Interaction of a G-protein beta-subunit with a conserved sequence in Ste20/PAK family protein kinases. Nature 180 9428767
2013 Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS. Nature methods 170 23455922
2014 Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. Proceedings of the National Academy of Sciences of the United States of America 167 25201988
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
2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Science signaling 162 25468996
2009 Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. Gut 157 19240061
2014 Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy. Molecular cell 156 25544559
2014 STRIPAK components determine mode of cancer cell migration and metastasis. Nature cell biology 148 25531779
1995 Shk1, a homolog of the Saccharomyces cerevisiae Ste20 and mammalian p65PAK protein kinases, is a component of a Ras/Cdc42 signaling module in the fission yeast Schizosaccharomyces pombe. Proceedings of the National Academy of Sciences of the United States of America 145 7597098
2005 Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3. Molecular and cellular biology 140 16314523
1996 Activation of a human Ste20-like kinase by oxidant stress defines a novel stress response pathway. The EMBO journal 131 8887545
2000 SPAK, a STE20/SPS1-related kinase that activates the p38 pathway. Oncogene 122 10980603
2011 MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases. The EMBO journal 121 21423148
1995 Cloning and characterization of a member of the MST subfamily of Ste20-like kinases. Gene 120 8566796
2008 Biosignaling of mammalian Ste20-related kinases. Cellular signalling 116 18255267
2012 Molecular physiology of SPAK and OSR1: two Ste20-related protein kinases regulating ion transport. Physiological reviews 115 23073627
2005 Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells. Molecular cell 91 16337592
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
2017 The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 28993483
2009 Happyhour, a Ste20 family kinase, implicates EGFR signaling in ethanol-induced behaviors. Cell 86 19464045
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
2015 Regulation of mammalian Ste20 (Mst) kinases. Trends in biochemical sciences 76 25665457
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 76 17596296
2001 Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase (NIK). Development (Cambridge, England) 76 11290295
1999 Induction of apoptosis by SLK, a Ste20-related kinase. Oncogene 76 10602516
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 72 19855390
2003 Poly(ADP-ribose) polymerase 1 and Ste20-like kinase hKFC act as transcriptional repressors for gamma-2 herpesvirus lytic replication. Molecular and cellular biology 70 14585985
2004 PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans. Molecular biology of the cell 69 15282344
1997 LOK is a novel mouse STE20-like protein kinase that is expressed predominantly in lymphocytes. The Journal of biological chemistry 68 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
1996 The highly conserved skb1 gene encodes a protein that interacts with Shk1, a fission yeast Ste20/PAK homolog. Proceedings of the National Academy of Sciences of the United States of America 64 8943016
1999 Human JIK, a novel member of the STE20 kinase family that inhibits JNK and is negatively regulated by epidermal growth factor. The Journal of biological chemistry 63 10559204
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 62 17114295
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
2010 The fatty acid synthase fasn-1 acts upstream of WNK and Ste20/GCK-VI kinases to modulate antimicrobial peptide expression in C. elegans epidermis. Virulence 49 21178429
2021 STK3/STK4 signalling in adipocytes regulates mitophagy and energy expenditure. Nature metabolism 48 33758424
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
2003 The Ste20 kinase MST4 plays a role in prostate cancer progression. Cancer research 47 12810671
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
2003 Comparative studies of a new subfamily of human Ste20-like kinases: homodimerization, subcellular localization, and selective activation of MKK3 and p38. Oncogene 45 13679851
2000 The Ste20 kinase misshapen regulates both photoreceptor axon targeting and dorsal closure, acting downstream of distinct signals. Molecular and cellular biology 45 10848599
2009 Crystal structure of domain-swapped STE20 OSR1 kinase domain. Protein science : a publication of the Protein Society 44 19177573
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
2005 Interaction with the SH3 domain protein Bem1 regulates signaling by the Saccharomyces cerevisiae p21-activated kinase Ste20. Molecular and cellular biology 41 15743816
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
2012 Ste20-like kinase SLK, at the crossroads: a matter of life and death. Cell adhesion & migration 39 23154402
2011 Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice. Journal of immunology (Baltimore, Md. : 1950) 38 21705622
2008 Nuclear factor-kappaB is a critical mediator of Ste20-like proline-/alanine-rich kinase regulation in intestinal inflammation. The American journal of pathology 38 18787102
2019 Comprehensive profiling of the STE20 kinase family defines features essential for selective substrate targeting and signaling output. PLoS biology 37 30897078
2007 Cdc42 and the Ste20-like kinase Don3 act independently in triggering cytokinesis in Ustilago maydis. Journal of cell science 37 18089648
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
2001 Androgens induce expression of SPAK, a STE20/SPS1-related kinase, in LNCaP human prostate cancer cells. Molecular and cellular endocrinology 36 11514053
2007 Caenorhabditis elegans WNK-STE20 pathway regulates tube formation by modulating ClC channel activity. EMBO reports 33 18049475
2004 An ste20 homologue in Ustilago maydis plays a role in mating and pathogenicity. Eukaryotic cell 33 14871948
2014 The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy. The Journal of biological chemistry 32 25035424
2012 A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3). The Biochemical journal 32 22229648
2009 Ste20-kinase-dependent TEDS-site phosphorylation modulates the dynamic localisation and endocytic function of the fission yeast class I myosin, Myo1. Journal of cell science 32 19808887
2005 The Ste20-like kinase misshapen functions together with Bicaudal-D and dynein in driving nuclear migration in the developing drosophila eye. Mechanisms of development 30 15582780
2005 Ste20/GCK kinase Nak1/Orb3 polarizes the actin cytoskeleton in fission yeast during the cell cycle. Journal of cell science 30 15731009
2021 Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer. Molecular therapy : the journal of the American Society of Gene Therapy 29 34450249
2012 Mammalian ste20-like kinase and SAV1 promote 3T3-L1 adipocyte differentiation by activation of PPARγ. PloS one 29 22292086
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 Inhibitors of the Hippo Pathway Kinases STK3/MST2 and STK4/MST1 Have Utility for the Treatment of Acute Myeloid Leukemia. Journal of medicinal chemistry 26 34807584
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
2009 p21-activated kinases Cla4 and Ste20 regulate vacuole inheritance in Saccharomyces cerevisiae. Eukaryotic cell 25 19218422
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
2008 Mammalian Ste20-like protein kinase 3 mediates trophoblast apoptosis in spontaneous delivery. Apoptosis : an international journal on programmed cell death 23 18040775
1997 Molecular cloning and characterization of a novel putative STE20-like kinase in guinea pigs. Archives of biochemistry and biophysics 23 9143322
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
2019 microRNA-222 promotes colorectal cancer cell migration and invasion by targeting MST3. FEBS open bio 21 31034165
2014 STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb. American journal of physiology. Renal physiology 21 25477470
2011 Regulation of the Ste20-like kinase, SLK: involvement of activation segment phosphorylation. The Journal of biological chemistry 21 22203681
2010 Structures of human MST3 kinase in complex with adenine, ADP and Mn2+. Acta crystallographica. Section D, Biological crystallography 21 20124694
2010 The Ste20 kinase misshapen is essential for the invasive behaviour of ovarian epithelial cells in Drosophila. EMBO reports 21 21102643
2009 The Ste20-like kinase SLK promotes p53 transactivation and apoptosis. American journal of physiology. Renal physiology 20 19640899