Affinage

STK4

Serine/threonine-protein kinase 4 · UniProt Q13043

Round 2 corrected
Length
487 aa
Mass
55.6 kDa
Annotated
2026-04-28
130 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STK4/MST1 is a stress-responsive serine/threonine kinase that functions as the core upstream kinase of the mammalian Hippo tumor-suppressor pathway and integrates apoptotic, autophagic, immune, and metabolic signaling. STK4 is autoactivated by Thr183 autophosphorylation within homodimers and is positively regulated by c-Abl (Y433 phosphorylation) and TRAF6 (ubiquitination), while Akt (Thr120), mTORC2 (Ser438), FGFR4, RASSF/NORE scaffolds, and SIRT7 act as negative regulators (PMID:12223493, PMID:15109305, PMID:19940129, PMID:25843706, PMID:30903103, PMID:32975614, PMID:38288904). Caspase-3 cleavage removes the C-terminal NES-containing domain, enabling nuclear translocation where STK4 phosphorylates histone H2B-Ser14 to drive chromatin condensation and phosphorylates FOXO transcription factors to promote apoptosis; in the cytoplasm, STK4 phosphorylates MOB1 to activate the LATS1/2–YAP1 cascade, phosphorylates Beclin1-Thr108 and LC3-Thr50 to regulate autophagy, phosphorylates Bcl-xL-Ser14 to activate Bax-dependent apoptosis, and phosphorylates PDX1-Thr11 to promote its degradation in pancreatic β-cells (PMID:9545236, PMID:12757711, PMID:16751106, PMID:18328708, PMID:24141421, PMID:25544559, PMID:24813943, PMID:24633305). In the immune system, STK4 operates through non-canonical Hippo pathways engaging MOB1–DOCK8–Rac1 and DOCK8–LRCH axes to control lymphocyte adhesion, migration, thymic egress, and Treg homeostasis, and it phosphorylates Foxp3-Ser418 to stabilize Foxp3–NF-κB p65 complexes essential for Treg function (PMID:19339990, PMID:22412158, PMID:30413360, PMID:36149942).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1998 High

    Establishing that STK4/MST1 is a caspase-3 substrate whose cleavage-mediated activation amplifies apoptosis resolved how this kinase is engaged during cell death and connected it to MAPK stress cascades.

    Evidence Caspase inhibitor experiments, overexpression of wild-type and truncated MST1 mutants, co-transfection kinase activation assays in mammalian cells

    PMID:9545236

    Open questions at the time
    • Physiological stimuli that initiate MST1 cleavage in non-apoptotic contexts were unknown
    • Endogenous downstream substrates had not been identified
  2. 2001 High

    Demonstrating that caspase cleavage removes C-terminal NES sequences to permit nuclear translocation explained how MST1 gains access to chromatin substrates during apoptosis.

    Evidence NES mutagenesis, leptomycin B treatment, staurosporine-induced apoptosis with nuclear localization and chromatin condensation assays

    PMID:11517310

    Open questions at the time
    • The nuclear substrate responsible for chromatin condensation remained unidentified
    • Whether non-caspase mechanisms could drive nuclear entry was unexplored
  3. 2002 High

    Mapping Thr183 as the primary activation-loop autophosphorylation site and showing that homodimerization drives intermolecular autoactivation defined the fundamental mechanism of MST1 self-activation, while the NORE1–MST1–Ras complex revealed scaffold-dependent membrane targeting as a Ras effector pathway.

    Evidence Systematic mutagenesis with in vitro kinase assays and cell-based apoptosis readouts; endogenous co-IP of NORE1–MST1–Ras with membrane-targeting constructs

    PMID:11864565 PMID:12223493

    Open questions at the time
    • Whether RASSF/NORE scaffolds activate or inhibit MST1 was debated
    • Physiological triggers of homodimerization in vivo were unclear
  4. 2003 High

    Identifying histone H2B-Ser14 as the direct nuclear substrate phosphorylated by caspase-cleaved MST1 provided the molecular mechanism for apoptotic chromatin condensation.

    Evidence In vitro kinase assay with recombinant proteins, phospho-specific antibody, caspase-3-deficient cell validation

    PMID:12757711

    Open questions at the time
    • Whether H2B-S14 phosphorylation has functions beyond apoptosis was unknown
    • Structural basis of MST1-H2B recognition was not resolved
  5. 2004 High

    Reconstituting RASSF/NORE-mediated suppression of Thr183 autophosphorylation in vitro clarified the dual role of these scaffolds: they inhibit soluble MST1 autoactivation but promote activity when membrane-targeted via Ras.

    Evidence In vitro autoactivation assays with purified recombinant NORE1A added directly, co-transfection with RASSF/NORE variants

    PMID:15109305

    Open questions at the time
    • Structural mechanism of SARAH-domain-mediated inhibition was not determined
    • In vivo significance of the dual scaffold function was untested
  6. 2005 High

    Demonstrating that the MST family directly phosphorylates LATS1/2 at conserved activating sites formally established the mammalian MST→LATS→YAP Hippo cascade.

    Evidence In vitro kinase assays with mass spectrometry phosphorylation site identification, MST2–hWW45 co-IP

    PMID:15688006

    Open questions at the time
    • Whether MST1 and MST2 are functionally redundant in this cascade was unresolved
    • Contribution of intermediary kinases (e.g., MAP4Ks) had not been assessed
  7. 2006 High

    Identifying FOXO phosphorylation (disrupting 14-3-3 binding and driving nuclear import) as an MST1 effector axis revealed a Hippo-independent branch linking MST1 to cell death and longevity programs, conserved from worms to mammals.

    Evidence In vitro kinase assay, 14-3-3 co-IP disruption, neuronal nuclear translocation, C. elegans RNAi and lifespan assays

    PMID:16751106

    Open questions at the time
    • Precise phosphorylation sites on different FOXO isoforms needed mapping
    • How cells choose between Hippo-YAP and FOXO outputs was unclear
  8. 2007 High

    Finding that MST1 physically binds and inhibits Akt1 in lipid rafts established a reciprocal antagonism (Akt inhibits MST1 at Thr120; MST1 inhibits Akt), forming a bistable apoptosis–survival switch.

    Evidence Co-IP from lipid raft fractions, siRNA knockdown, zebrafish rescue of Akt-induced phenotype

    PMID:17932490

    Open questions at the time
    • Molecular mechanism of MST1-mediated Akt inhibition was not defined
    • Relative contributions of full-length vs. caspase-cleaved MST1 fragments to Akt regulation were unclear
  9. 2008 High

    Identifying MOB1 as the preferred MST1/2 substrate that bridges MST1 to LATS1 activation during mitosis, and showing MST1 loss removes a proliferative brake on naïve T cells, extended the Hippo cascade mechanism and revealed its immune-regulatory arm.

    Evidence In vitro substrate identification, MST1/2 knockdown in cells, MOB-LATS1 co-IP, non-phosphorylatable MOB mutant; MST1 KO mouse T cell proliferation assays

    PMID:18328708 PMID:19073936

    Open questions at the time
    • Whether MOB1 is the sole mediator of MST1 effects on T cell proliferation was unknown
    • MOB1 phosphorylation sites relevant to LATS1 binding needed precise identification
  10. 2009 High

    MST1 was shown to control lymphocyte firm adhesion and motility in vivo through integrin regulation and to mediate Akt-dependent inhibitory phosphorylation at Thr120, together explaining how survival signaling suppresses MST1 and how MST1 loss impairs immune cell trafficking.

    Evidence MST1 KO mouse with intravital imaging and in vitro adhesion assays under shear flow; in vitro Akt kinase assay with Thr120 mutagenesis and tumor tissue immunoblotting

    PMID:19339990 PMID:19940129

    Open questions at the time
    • Downstream effectors linking MST1 to integrin inside-out signaling in lymphocytes were uncharacterized
    • Whether Thr120 phosphorylation controls nuclear localization independently of Thr183 was untested
  11. 2009 High

    Revealing that MST1 phosphorylates NDR1 at its hydrophobic motif via MOB1 to control centriole duplication expanded the MST1 kinase cascade beyond LATS to another AGC kinase family member.

    Evidence RNAi depletion with rescue, co-IP, in vitro phosphorylation, centrosome counting

    PMID:19836237

    Open questions at the time
    • Whether NDR kinases contribute to MST1 functions in non-mitotic contexts was unknown
    • Structural basis of MOB1-dependent NDR1 activation by MST1 was not resolved
  12. 2010 High

    Demonstrating that MST1 directly phosphorylates and inhibits Aurora B kinase to stabilize kinetochore-microtubule attachments established MST1 as a mitotic fidelity regulator beyond the canonical Hippo cascade.

    Evidence siRNA depletion, in vitro kinase assay of MST1 on Aurora B, chromosome alignment and spindle checkpoint assays

    PMID:20171103

    Open questions at the time
    • Phosphorylation site on Aurora B was not mapped
    • Relative contributions of MST1 vs. MST2 to mitotic Aurora B regulation were unclear
  13. 2010 High

    Identification of PHLPP phosphatases as MST1 activators (dephosphorylating inhibitory Thr387) placed MST1 at the center of a PHLPP–Akt–MST1 regulatory triangle controlling apoptosis/proliferation balance.

    Evidence Co-IP, in vitro phosphatase activity assay, kinase activation, siRNA knockdown

    PMID:20513427

    Open questions at the time
    • Whether Thr387 is the same or different from the Akt-targeted Thr120 site needed clarification across cell types
    • In vivo validation in animal models was lacking
  14. 2011 High

    c-Abl was identified as a positive regulator that phosphorylates MST1 at Y433 to stabilize and activate it under oxidative stress, while CHIP-mediated ubiquitination degrades unphosphorylated MST1, establishing a tyrosine kinase–regulated MST1 stability control.

    Evidence In vitro kinase assay, CHIP ubiquitination assay, phospho-Y433 antibody, primary hippocampal neuron model

    PMID:21715626

    Open questions at the time
    • Whether c-Abl and FGFR4 compete for the same Y433 site with opposite functional outcomes needed investigation
    • CHIP E3 ligase selectivity for MST1 was not structurally characterized
  15. 2012 High

    Genetic demonstration that MST1/2 control thymic egress via MOB1-dependent DOCK8 activation of Rac1/RhoA provided the mechanistic link between MST1 kinase activity and immune cell migration through non-canonical Hippo signaling.

    Evidence Conditional double-KO mouse, GTPase activity assays, DOCK8 co-IP, thymic egress measurement

    PMID:22412158

    Open questions at the time
    • Whether DOCK8-Rac1 axis operates in non-lymphoid cell migration downstream of MST1 was unknown
    • Direct phosphorylation of DOCK8 by MOB1-associated kinase was not shown
  16. 2013 High

    Demonstrating that MST1 phosphorylates Beclin1-Thr108 to strengthen Beclin1–Bcl-2 interaction and inhibit the Vps34 PI3K complex established MST1 as a direct autophagy inhibitor, distinct from its pro-apoptotic function.

    Evidence In vitro kinase assay, co-IP, PI3K activity assay, MST1 transgenic and KO mice after myocardial infarction, human cardiomyopathy tissue

    PMID:24141421

    Open questions at the time
    • How MST1 simultaneously inhibits autophagy via Beclin1 and promotes autophagosome maturation via LC3 was paradoxical
    • Tissue-specific regulation of these opposing autophagy outputs was unresolved
  17. 2014 High

    A suite of discoveries expanded the MST1 substrate repertoire: LC3-Thr50 phosphorylation promotes autophagosome-lysosome fusion, PDX1-Thr11 phosphorylation drives β-cell dysfunction, Bcl-xL-Ser14 phosphorylation activates mitochondrial apoptosis, and MST1/SAV1 promotes ciliogenesis through Aurora A phosphorylation and NPHP complex engagement.

    Evidence In vitro kinase assays with phosphomimetic rescue (LC3), MST1 KO mice in diabetes models (PDX1), mitochondrial fractionation and Bcl-xL–Bax co-IP (Bcl-xL), MST1/AURKA co-IP and zebrafish morpholino (cilia)

    PMID:24633305 PMID:24813943 PMID:25367221 PMID:25544559

    Open questions at the time
    • Whether LC3-Thr50 phosphorylation is required for all autophagy or only selective autophagy was unresolved
    • Structural basis of MST1-SAV1 engagement with the NPHP transition zone complex was not determined
  18. 2015 High

    MST1 was shown to dampen TLR-NF-κB signaling by phosphorylating and degrading IRAK1 while promoting bactericidal ROS through Rac-dependent TRAF6-ECSIT mitochondrial recruitment, and mTORC2 was identified as a direct negative regulator phosphorylating MST1-Ser438 in the SARAH domain.

    Evidence Co-IP and in vitro kinase assay (IRAK1), conditional macrophage KO (IRAK1 and ROS), in vitro mTORC2 kinase assay and cardiac-specific Rictor KO

    PMID:25843706 PMID:26414765 PMID:26457732

    Open questions at the time
    • Whether mTORC2 inhibition of MST1 is relevant in immune cells was untested
    • How MST1 coordinates opposing IRAK1 degradation and TRAF6-ECSIT activation in the same macrophage was unclear
  19. 2016 High

    Development of XMU-MP-1 as a selective MST1/2 inhibitor with validated cocrystal structure enabled pharmacological dissection and demonstrated that MST1/2 inhibition promotes tissue regeneration, while H-Ras–ERK-driven MST1/MST2 heterodimerization was shown to suppress Hippo signaling.

    Evidence X-ray cocrystal structure, biochemical kinase assay, mouse liver/intestinal injury models; endogenous co-IP of MST1/2 heterodimers with in vitro kinase comparison

    PMID:27238285 PMID:27535619

    Open questions at the time
    • Off-target effects of XMU-MP-1 on related kinases in vivo needed broader profiling
    • Whether heterodimerization is reversible and dynamically regulated during tumorigenesis was unresolved
  20. 2017 High

    Biophysical mapping revealed that RASSF proteins engage both the SARAH and kinase domains of MST1, and that RASSF binding switches substrate preference — enhancing H2B phosphorylation while suppressing FOXO signaling — providing a substrate-selection mechanism.

    Evidence Surface plasmon resonance domain mapping, in vitro kinase assays comparing H2B and FOXO phosphorylation in RASSF–MST1 complexes

    PMID:28327630

    Open questions at the time
    • Structural basis for RASSF-induced substrate switching was not resolved
    • In vivo relevance of this substrate-selection mechanism remained untested
  21. 2018 High

    Quantitative proteomics of MST1 interactors in Treg cells identified the DOCK8-LRCH cytoskeletal module and demonstrated that MST1 senses IL-2 to promote Rac-STAT5 activation for Treg homeostasis, establishing a non-canonical immune-specific MST1 pathway.

    Evidence Treg-specific KO mice, quantitative proteomics, STAT5 phosphorylation and Rac GTPase assays

    PMID:30413360

    Open questions at the time
    • Direct phosphorylation targets linking MST1 to DOCK8-LRCH were not identified
    • Whether this pathway operates in other immune lineages was unknown
  22. 2019 High

    FGFR4 was identified as a second tyrosine kinase (after c-Abl) that phosphorylates MST1-Y433 but with an inhibitory outcome, and the ROS–MST1–FOXO1 axis was shown to drive endothelial tip cell polarity during sprouting angiogenesis.

    Evidence Mass spectrometry site identification and Y433F mutagenesis for FGFR4; endothelial-specific MST1/FOXO1 KO mice with retinal angiogenesis assays

    PMID:30783090 PMID:30903103

    Open questions at the time
    • How the same Y433 site mediates opposite outcomes depending on the upstream kinase required structural clarification
    • Whether MST1-FOXO1 controls angiogenesis in pathological settings beyond retinopathy was unknown
  23. 2020 High

    TRAF6-mediated K63-ubiquitination was shown to activate MST1 in macrophages during LPS signaling, with activated MST1 feeding back to suppress TRAF6 autoubiquitination, and MST1 was found to phosphorylate UNC5B-Thr428 downstream of netrin1 loss to drive dopaminergic neuronal death.

    Evidence Ubiquitination assay and myeloid-specific KO with sepsis model; in vitro kinase assay on UNC5B, UNC5B KO mouse, human PD brain tissue

    PMID:32929029 PMID:32975614

    Open questions at the time
    • Whether MST1 ubiquitination is regulated by deubiquitinases other than USP46 in macrophages was unexplored
    • Therapeutic potential of MST1 inhibition in Parkinson's disease was not tested
  24. 2021 High

    MST3/STK4 were identified as suppressors of mitochondrial capacity in adipocytes through BNIP3-dependent mitophagy regulation, and USP46 was shown to stabilize MST1 by deubiquitination to maintain Hippo signaling in HCC.

    Evidence Adipocyte-specific double KO mice with BNIP3 phosphorylation and mitochondrial function assays; USP46-MST1 co-IP, ubiquitination assay, HCC xenograft

    PMID:33758424 PMID:34029571

    Open questions at the time
    • Direct BNIP3 phosphorylation sites targeted by STK4 were not mapped
    • USP46-MST1 interaction awaits independent confirmation
  25. 2022 High

    STK4 was shown to form a nuclear complex with NF-κB p65 and Foxp3 in Treg cells, directly phosphorylating Foxp3-Ser418 to stabilize this complex, and SIRT7 was identified as a dual negative regulator (transcriptional repression and deacetylation-dependent degradation of MST1 protein).

    Evidence Co-IP of STK4-p65-Foxp3 complex, in vitro kinase assay, phosphomimetic rescue in Treg-specific KO mice; ChIP, mass spectrometry of deacetylation sites, ubiquitination assay in HCC

    PMID:36149942 PMID:38288904

    Open questions at the time
    • Whether Foxp3-Ser418 phosphorylation is sufficient for Treg stability without other STK4 outputs was unknown
    • In vivo validation of SIRT7-dependent MST1 regulation beyond HCC was lacking
  26. 2023 High

    Identification of Nur77-Thr366 as an MST1 substrate controlling endometrial receptivity extended MST1 function to reproduction and implantation biology.

    Evidence In vitro kinase assay with LC-MS/MS site identification, phospho-specific antibody, embryo adhesion assays, mouse delayed implantation model, clinical samples from recurrent implantation failure

    PMID:36623453

    Open questions at the time
    • Whether MST1-Nur77 signaling operates in other Nur77-expressing tissues is unexplored
    • Upstream signals activating MST1 in the uterus during implantation are undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How STK4/MST1 integrates its diverse substrate repertoire in a single cell — choosing between Hippo-YAP, FOXO, autophagy, and immune-specific outputs — and how scaffold proteins, post-translational modifications, and subcellular compartmentalization orchestrate this context-dependent substrate selection remain the central unresolved mechanistic questions.
  • No unified structural or systems-level model explains context-dependent MST1 substrate selection
  • Full-length MST1 structure including SARAH domain in complex with regulatory partners is unavailable
  • Relative quantitative contributions of MST1 vs. MST2 in each tissue context have not been systematically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 18 GO:0016740 transferase activity 13 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005694 chromosome 1 GO:0005929 cilium 1
Pathway
R-HSA-5357801 Programmed Cell Death 10 R-HSA-162582 Signal Transduction 9 R-HSA-168256 Immune System 8 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-9612973 Autophagy 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
DOCK8FOXO3LATS1MOB1ARASSF1ARASSF5SAV1TRAF6
Complex memberships
DOCK8-LRCHs-MST1 (immune cytoskeletal module)MST1-RASSF1A/RASSF5 (SARAH domain scaffold complex)MST1/SAV1 (Hippo core complex)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MST1 (STK4) is specifically cleaved by caspase-3-like activity during apoptosis, removing the C-terminal regulatory domain and activating the kinase. Overexpression of wild-type or truncated (caspase-cleaved) MST1 induces apoptotic morphological changes; kinase-dead MST1 does not. MST1 activates MKK6, p38 MAPK, MKK7, and SAPK in co-transfection assays, suggesting a positive feedback loop amplifying apoptosis. Caspase inhibitor experiments (ZVAD-fmk, DEVD-CHO, CrmA), overexpression of wild-type and truncated mutants, co-transfection kinase activation assays The EMBO journal High 9545236
2001 Full-length MST1 is excluded from the nucleus by two functional nuclear export signals (NESs) in its C-terminal domain. Caspase-mediated cleavage releases this domain, enabling nuclear translocation of the N-terminal kinase domain where MST1 promotes chromatin condensation. Mutation of cleavage sites reduces chromatin condensation ability. NES mutation, leptomycin B treatment, staurosporine-induced apoptosis, nuclear localization assays, chromatin condensation assay Proceedings of the National Academy of Sciences of the United States of America High 11517310
2002 MST1 activation requires autophosphorylation at Thr183 (primary activation site) in kinase subdomain VIII via intermolecular autophosphorylation enhanced by homodimerization. Thr187 is also critical for activity. Active MST1 additionally autophosphorylates at Thr177 and Thr387. Kinase activity (not caspase cleavage) is required for apoptotic phenotypes including JNK, caspase-3, and caspase-9 activation. Phosphorylation site mapping by mutagenesis, in vitro kinase assays, cell-based apoptosis assays with kinase-dead and phosphomimetic mutants The Journal of biological chemistry High 12223493
2002 MST1 forms a constitutive complex in vivo with NORE1 (RASSF5/NORE1A), and this NORE1-MST1 complex associates with endogenous Ras after serum stimulation. Membrane-targeting of MST1 through NORE or myristoylation augments its apoptotic efficacy. The NORE-MST1 complex mediates the proapoptotic effect of Ki-RasG12V. Co-immunoprecipitation of endogenous proteins, membrane-targeting constructs, apoptosis assays with dominant-negative MST1 C-terminal fragment Current biology : CB High 11864565
2003 Caspase-cleaved MST1 phosphorylates histone H2B at serine 14 (S14) in vitro and in vivo, and this phosphorylation is dependent on caspase-3-mediated cleavage of MST1. H2B-S14 phosphorylation is a hallmark of apoptotic chromatin condensation conserved from frogs to humans. In vitro kinase assay with recombinant MST1 and H2B, phospho-specific antibody, caspase-3-deficient cell experiments Cell High 12757711
2004 MST1 undergoes robust intramolecular autophosphorylation at Thr183 within MST1 dimers in vitro. RASSF1A, RASSF1C, NORE1A, and NORE1B suppress MST1 Thr183 phosphorylation and abolish Mg-ATP-mediated autoactivation in vitro and in vivo; direct addition of purified NORE1A also inhibits MST1 activation in vitro. Membrane-targeted NORE1A and Ras(G12V)-bound NORE1A enhance MST1 activation. In vitro autoactivation assays with recombinant proteins, co-transfection with RASSF/NORE polypeptides, phospho-specific immunoblotting The Biochemical journal High 15109305
2005 MST2 (and by extension the MST1/2 family) directly phosphorylates and activates LATS1 and LATS2 at conserved sites S909 (activation loop) and T1079 (hydrophobic motif). MST2 directly interacts with hWW45/SAV1. This establishes the mammalian Hippo kinase cascade: MST→LATS. In vitro kinase assays, mass spectrometry phosphorylation site identification, deletion analysis, Co-IP of MST2 with hWW45 Oncogene High 15688006
2006 MST1 directly phosphorylates FOXO transcription factors at a conserved site within the forkhead domain (FOXO3 Ser207), disrupting their interaction with 14-3-3 proteins and promoting nuclear translocation, thereby inducing neuronal cell death. This MST-FOXO signaling axis is evolutionarily conserved (also functions in C. elegans via CST-1/DAF-16) and mediates oxidative stress responses and longevity. In vitro kinase assay, phospho-specific antibody, 14-3-3 co-IP disruption, nuclear translocation assays in primary neurons, C. elegans RNAi and lifespan assays Cell High 16751106
2008 MST1 and MST2 are activated during mitosis (especially in nocodazole-arrested cells). MOBKL1A and MOBKL1B are preferred MST1/MST2 substrates identified in vitro, phosphorylated in an MST1/MST2-dependent manner during mitosis and in response to okadaic acid or H2O2. MST1/MST2-catalyzed MOB phosphorylation promotes MOB binding to LATS1 and enables LATS1 activation loop phosphorylation. Non-phosphorylatable MOB mutant accelerates cell proliferation by speeding G1/S and mitotic exit. In vitro kinase assay substrate identification, cell-based phosphorylation (MST1/2 knockdown), co-IP (MOB-LATS1), non-phosphorylatable mutant rescue experiments, cell cycle analysis Current biology : CB High 18328708
2008 The Nore1B/RAPL-MST1 complex is a negative regulator of naïve T cell proliferation. MST1 deficiency eliminates Nore1B/RAPL protein in lymphoid cells (without affecting MST2). Loss of MST1 removes a barrier to naïve T cell activation and proliferation. Among known substrates, only MOBKL1A/B phosphorylation is lost entirely in TCR-stimulated MST1-deficient T cells, and MST1/2-catalyzed MOB phosphorylation contributes to the anti-proliferative action in naïve T cells. MST1 knockout mouse model, T cell proliferation assays, phosphorylation analysis of endogenous substrates, LFA-1 clustering Proceedings of the National Academy of Sciences of the United States of America High 19073936
2009 MST1 and MST2 are cleaved and constitutively activated in quiescent mouse liver (non-apoptotic context). Combined Mst1/2 deficiency leads to loss of inhibitory Ser127 phosphorylation on YAP1, massive liver overgrowth, and hepatocellular carcinoma. MST1 re-expression in HCC cell lines promotes YAP1 Ser127 phosphorylation and abrogates tumorigenicity. MST1/2 inactivates YAP1 in liver through an intermediary kinase distinct from LATS1/2. Conditional knockout mouse models, re-expression in HCC cell lines, YAP1 phosphorylation analysis, tumor suppression assays Cancer cell High 19878874
2009 MST1 phosphorylates FOXO1 at Ser212, disrupting FOXO1 association with 14-3-3 proteins and promoting FOXO1 nuclear translocation in primary cerebellar granule neurons deprived of neuronal activity. MST1-induced cell death requires FOXO1, and the scaffold protein Nore1 is required for survival factor deprivation-induced neuronal death downstream of MST1. In vitro kinase assay, 14-3-3 co-IP, nuclear translocation assays in primary neurons, siRNA knockdown, cell death assays The Journal of biological chemistry High 19221179
2009 MST1 controls lymphocyte trafficking in vivo: Mst1-/- lymphocytes exhibit impaired firm adhesion to high endothelial venules, reduced stopping time on endothelium under physiological shear flow, defective stabilization of adhesion through α4 integrins, and impaired motility over stromal cells and within lymph nodes. MST1 deficiency does not affect L-selectin-dependent rolling. Mst1 knockout mouse, intravital and in vitro adhesion cascade assays under physiological shear flow, two-photon imaging The EMBO journal High 19339990
2009 MST1 controls centrosome/centriole duplication through an MST1→MOB1→NDR1 signaling pathway. MST1 phosphorylates NDR1 at the hydrophobic motif (Thr444), which requires MOB1/NDR1 complex formation. RNAi depletion of MST1 or MOB1 impairs centriole duplication; overexpression of MOB1 causes centrosome overduplication. MST1 kinase activity (but not its binding to SAV or RASSF1A) is required. RNAi depletion, shRNA-resistant mutant rescue, co-IP, in vitro phosphorylation, centrosome counting Current biology : CB High 19836237
2007 MST1/STK4 is a physiological Akt1 interaction partner identified in lipid raft-enriched fractions. Endogenous MST1 and MST2 act as inhibitors of endogenous Akt1. Both full-length MST1 and its two caspase cleavage products (N-terminal and C-terminal fragments) complex with and inhibit Akt1. MST1 cRNA reverts a lethal zebrafish phenotype induced by membrane-targeted Akt1. Co-IP from lipid rafts, siRNA knockdown of endogenous MST1/2 on Akt1 activity, zebrafish rescue assay The EMBO journal High 17932490
2009 Akt phosphorylates MST1 at a conserved Thr120 residue, inhibiting MST1 kinase activity and blocking its nuclear translocation and Thr183 autophosphorylation. Phospho-MST1-Thr120 fails to activate downstream FOXO3a and JNK. Inverse correlation between pMST1-Thr120 and pMST1-Thr183 is observed in human ovarian tumors. In vitro Akt kinase assay, mutagenesis, nuclear localization assay, downstream substrate activation assays, tumor sample immunoblotting The Journal of biological chemistry High 19940129
2010 PHLPPs (PHLPP1 and PHLPP2) interact with MST1 both in vivo and in vitro, and dephosphorylate MST1 at the inhibitory Thr387 site, activating MST1 and its downstream effectors p38 and JNK to induce apoptosis. Akt phosphorylates the same Thr387 site to inhibit MST1. PHLPP, Akt, and MST1 form an autoinhibitory triangle controlling apoptosis/proliferation balance. Co-IP (in vivo and in vitro), phosphatase activity assays, kinase activation assays, siRNA knockdown Molecular cell High 20513427
2010 MST1 limits Aurora B kinase activity to promote stable kinetochore-microtubule attachment. MST1 depletion causes increased Aurora B activity, unaligned chromosomes, and spindle checkpoint activation. MST1 directly phosphorylates Aurora B and inhibits its kinase activity in vitro. MST1 and NDR1 associate with Aurora B; NDR1 depletion phenocopies MST1 depletion. MST1 siRNA depletion, in vitro kinase assay (MST1 on Aurora B), chromosome alignment assay, Aurora B activity assay Current biology : CB High 20171103
2011 The tyrosine kinase c-Abl phosphorylates MST1 at Y433, triggering MST1 stabilization and activation. Inhibition of c-Abl promotes CHIP-mediated ubiquitination and degradation of MST1. Oxidative stress induces c-Abl-dependent tyrosine phosphorylation of MST1 and increases MST1-FOXO3 interaction, activating the MST1-FOXO signaling pathway to cause neuronal cell death. In vitro kinase assay, co-IP, CHIP ubiquitination assay, phospho-specific antibody, rat hippocampal neuron model The Journal of neuroscience High 21715626
2012 Mst1 and Mst2 control Rho GTPase activation and thymic egress of mature thymocytes. Double KO SP thymocytes show abolished sphingosine-1-phosphate- and CCL21-induced Mob1 phosphorylation, Rac1 and RhoA GTP charging, and subsequent cell migration. Phosphorylated Mob1 binds and activates the Rac1 guanyl nucleotide exchanger Dock8, which is abundant in the thymus. Conditional double-knockout mouse model, GTPase activity assays (GTP-Rac1/RhoA), Mob1 phosphorylation assays, Dock8 co-IP, thymus egress assays The Journal of experimental medicine High 22412158
2013 Mst1 inhibits autophagy by phosphorylating Beclin1 at Thr108 in the BH3 domain, enhancing Beclin1 interaction with Bcl-2 and Bcl-xL, stabilizing the Beclin1 homodimer, and inhibiting the Atg14L-Beclin1-Vps34 PI3K complex. Simultaneously, Bcl-2/Bcl-xL sequestration by Beclin1 allows Bax activation and apoptosis. Mst1 transgenic mice show Thr108-phosphorylated Beclin1 accumulation after myocardial infarction. In vitro kinase assay, phospho-Thr108 Beclin1 antibody, co-IP (Beclin1-Bcl-2/Bcl-xL), PI3K activity assay, Mst1 transgenic and KO mice, human cardiomyopathy samples Nature medicine High 24141421
2014 STK4/MST1 phosphorylates LC3 at Thr50, which is essential for autophagosome-lysosome fusion. Loss of this phosphorylation blocks autophagy and impairs clearance of intracellular bacteria. A phosphomimetic LC3-T50E mutation reverses the autophagy block in STK3/STK4-deficient cells, restoring bacterial clearance. This function is conserved across species. In vitro kinase assay (STK4 on LC3), phosphomimetic mutant rescue, autophagy flux assays, bacterial clearance assays, STK3/STK4 knockout cells Molecular cell High 25544559
2014 MST1 directly phosphorylates PDX1 at Thr11, leading to PDX1 ubiquitination and proteasomal degradation, impairing insulin secretion. MST1 also upregulates BIM (a BH3-only protein) to promote mitochondrial apoptosis in beta cells. MST1 deficiency restores normoglycemia and beta cell function in diabetic mouse models. In vitro kinase assay, phospho-specific antibody, co-IP, ubiquitination assay, MST1 KO and transgenic mice, islet transplantation Nature medicine High 24633305
2014 Mst1 promotes cardiac myocyte apoptosis by phosphorylating Bcl-xL at Ser14 (in the BH4 domain), antagonizing Bcl-xL-Bax binding and causing Bax activation and mitochondrial apoptosis. A signaling cassette of K-Ras, RASSF1A scaffold, and Mst1 localizes to mitochondria and drives Mst1 activation in response to oxidative stress. In vitro kinase assay, phospho-Ser14 Bcl-xL antibody, co-IP (Bcl-xL-Bax), mitochondrial fractionation, oxidative stress assays Molecular cell High 24813943
2014 MST1/SAV1 complex promotes ciliogenesis. MST1 localizes to the basal body of cilia and is activated during ciliogenesis. MST1/2 promote ciliogenesis through two mechanisms: (1) MST1/2 bind and phosphorylate Aurora A, leading to dissociation of the AURKA/HDAC6 cilia-disassembly complex; (2) MST1/2-SAV1 associate with the NPHP transition-zone complex, promoting ciliary cargo localization. Depletion of MST1/2 or SAV1 impairs ciliogenesis in cells and induces ciliopathy phenotypes in zebrafish. Co-IP (MST1-AURKA, MST1/2-SAV1-NPHP complex), in vitro kinase assay, siRNA depletion, zebrafish morpholino knockdown, live-cell imaging Nature communications High 25367221
2015 MST1 regulates IRAK1 degradation: STK4 binds to and phosphorylates IRAK1, leading to IRAK1 degradation, thereby dampening TLR4/9-induced proinflammatory cytokine secretion while enhancing TLR3/4-triggered IFN-β production in macrophages. Macrophage-specific Stk4 deletion leads to chronic inflammation, liver fibrosis, and HCC in mice. Co-IP (STK4-IRAK1), in vitro kinase/phosphorylation assay, macrophage-conditional KO mice, cytokine ELISA, liver fibrosis/HCC model The Journal of clinical investigation High 26457732
2015 Mst1 and Mst2 control phagosome-mitochondrion juxtaposition and ROS production in macrophages. Mst1/2 activate the GTPase Rac to promote TLR-triggered assembly of the TRAF6-ECSIT complex required for mitochondria recruitment to phagosomes. Inactive Rac2(D57N) disrupts the TRAF6-ECSIT complex by sequestering TRAF6, diminishing ROS production. Mst1/2 conditional KO macrophages, GTPase activity assays, co-IP (TRAF6-ECSIT), ROS measurement, bacterial killing assays Nature immunology High 26414765
2015 mTORC2 (Rictor complex) directly phosphorylates MST1 at Ser438 in the SARAH domain, reducing MST1 homodimerization and kinase activity. Cardiac-specific Rictor deletion leads to marked MST1 activation, cardiac dysfunction and dilation, impairing cardiac adaptation to pressure overload. In vitro mTORC2 kinase assay on MST1, phospho-Ser438 antibody, homodimerization assay, cardiac-specific Rictor KO mice, pressure overload model Cell reports High 25843706
2016 A reversible, selective MST1/2 inhibitor XMU-MP-1 was identified; cocrystal structure confirmed on-target binding. XMU-MP-1 blocks MST1/2 kinase activities, activates YAP, and promotes cell growth. In vivo, XMU-MP-1 augments mouse intestinal and liver repair/regeneration and enhances human hepatocyte repopulation in Fah-deficient mice. Biochemical kinase inhibition assay, X-ray cocrystal structure, structure-activity relationship, YAP activation assay, mouse liver/intestinal injury models Science translational medicine High 27535619
2016 MST1 phosphorylates eIF4E, causing eIF4E to weakly interact with the 5' CAP and inhibit mRNA translation of a subset of mRNAs. Simultaneously, MST1-mediated eIF4E phosphorylation increases lncRNA association with active polysomes. TNF-α-induced MST1 activation triggers production of a micropeptide STORM via this eIF4E phosphorylation pathway. In vitro kinase assay (MST1 on eIF4E), cap-binding assay, polyribosome fractionation, TNF-α stimulation assays Biochimica et biophysica acta. Gene regulatory mechanisms Medium 28487214
2016 H-ras, via ERK-dependent signaling, promotes MST1/MST2 heterodimerization through their SARAH domains. Mst1/Mst2 heterodimers have markedly reduced kinase activity compared to homodimers. Cells lacking Mst1 (where Mst1/Mst2 heterodimers cannot form) are resistant to H-ras-mediated transformation and maintain active Hippo signaling. Co-IP of endogenous Mst1/Mst2, in vitro kinase assay comparing homo- vs heterodimers, Mst1-/- and Mst1/2-/- cell lines, H-ras transformation assays Current biology : CB High 27238285
2017 RASSF1A and RASSF5 interact with MST1 not only through the SARAH domain but also through the N-terminal kinase domain of MST1. RASSF5 is a preferred partner over RASSF1A. The RASSF-MST1 complex switches MST1 activity: complexed MST1 positively regulates H2B-Ser14 phosphorylation (chromatin condensation) but suppresses MST1-FoxO signaling. Surface plasmon resonance (SPR) domain mapping, in vitro kinase assay with RASSF-MST1 complexes, H2B and FoxO phosphorylation assays Scientific reports High 28327630
2018 Mst1 and Mst2 in Treg cells sense IL-2 signals to promote STAT5 activation necessary for Treg cell homeostasis and lineage stability. Mst1 deficiency limits Treg cell migration and access to IL-2 and activity of Rac GTPase, which mediates downstream STAT5 activation. Unbiased proteomics revealed Mst1 association with the cytoskeletal DOCK8-LRCHs module. Treg-specific KO mice, quantitative proteomics (Mst1 interactome), STAT5 phosphorylation assays, Rac GTPase activity, Treg migration assays Immunity High 30413360
2019 FGFR4 phosphorylates MST1 at Y433 in a kinase activity-dependent manner (verified by mass spectrometry), and blocking this phosphorylation (Y433F mutation) induces MST1 activation, increased threonine phosphorylation of MST1/2 and MOB1. FGFR4 knockdown/inhibition leads to enhanced MST1/2 activation, MST1 nuclear localization, and generation of N-terminal cleaved and autophosphorylated MST1, coincident with apoptosis induction. Kinase substrate screen, mass spectrometry phosphorylation site identification, Y433F mutagenesis, FGFR4 knockdown/inhibitor, nuclear localization imaging, apoptosis assays Cell death and differentiation High 30903103
2019 MST1-FOXO1 cascade is essential for directional migration of tip endothelial cells toward hypoxic regions during sprouting angiogenesis. MST1 is activated by mitochondrial ROS produced in response to hypoxia, and activated MST1 promotes nuclear import of FOXO1, augmenting transcriptional regulation of polarity and migration-associated genes. Endothelial-specific deletion of either MST1 or FOXO1 causes loss of tip cell polarity and impaired sprouting. Endothelial-specific KO mice, retinal angiogenesis assays, ROS measurement, FOXO1 nuclear translocation imaging, oxygen-induced retinopathy model Nature communications High 30783090
2019 STK4/MST1 phosphorylates BECN1 at Thr108 in its BH3 domain, and this phosphorylation increases BECN1 affinity for BCL2 and BCL2L1. Crystal structures of BCL2 and BCL2L1 with T108-modified BECN1 BH3 peptides were determined. Biophysical studies showed that phospho-T108 BECN1 shows increased but modest (<2-fold) affinity for anti-apoptotic proteins, and membrane/detergent environments can further stabilize the interaction. X-ray crystallography, surface plasmon resonance, microscale thermophoresis, molecular dynamics simulations Autophagy High 30626284
2020 Netrin1 reduction activates MST1, which phosphorylates the netrin receptor UNC5B at Thr428, promoting UNC5B apoptotic signaling and dopaminergic neuronal loss. Knockout of UNC5B abolishes netrin depletion-induced dopaminergic loss; blockade of MST1 phosphorylation of UNC5B suppresses neuronal apoptosis. Netrin1 is reduced in PD patient brains, associated with MST1 activation and UNC5B-T428 phosphorylation. In vitro kinase assay (MST1 on UNC5B), UNC5B phospho-T428 antibody, UNC5B KO mouse, MST1 inhibitor, human PD brain samples Proceedings of the National Academy of Sciences of the United States of America High 32929029
2020 STK4 (MST1/STK4) is ubiquitinated by TRAF6 in response to LPS, and this ubiquitination activates MST1/STK4. Activated MST1/STK4 inhibits TRAF6 autoubiquitination and downstream NF-κB signaling, functioning as a negative feedback regulator of LPS-induced inflammation. Myeloid-specific genetic ablation of MST1/STK4 increased susceptibility to LPS-induced septic shock. Ubiquitination assay, co-IP (TRAF6-MST1), myeloid-specific KO mice, NF-κB activation assay, cytokine measurement Cellular and molecular life sciences High 32975614
2021 STK3 and STK4 are physiological suppressors of mitochondrial capacity in adipocytes. Genetic inactivation of Stk3/Stk4 increases mitochondrial mass and function and stabilizes UCP1 in beige adipose tissue. Mechanistically, STK3/STK4 regulate phosphorylation and dimerization status of the mitophagy receptor BNIP3, thereby promoting adipocyte mitophagy. Adipocyte-specific double KO mice, mitochondrial function assays, BNIP3 phosphorylation and dimerization assays, XMU-MP-1 pharmacological inhibition, high-fat diet mouse model Nature metabolism High 33758424
2021 USP46 deubiquitinase directly binds MST1 and decreases its ubiquitination, stabilizing the MST1 protein and promoting MST1 kinase activity to suppress YAP1 and HCC progression. Co-IP (USP46-MST1), ubiquitination assay, MST1 protein stability assay, YAP1 activity assay, in vivo HCC xenograft Experimental cell research Medium 34029571
2022 TCR signaling in Treg cells induces nuclear translocation of STK4, leading to formation of an STK4-NF-κB p65-Foxp3 transcriptional complex. STK4 directly phosphorylates Foxp3 at Ser418, stabilizing the complex. STK4 deficiency in Treg cells precipitates fatal autoimmune disease with defective p65-Foxp3 complex formation. Overexpression of p65 or phosphomimetic Foxp3-S418E rescues defects in STK4-deficient Treg cells. Co-IP (STK4-p65-Foxp3), in vitro kinase assay (STK4 on Foxp3-S418), phosphomimetic rescue, Treg-specific KO mice, adoptive transfer model Science immunology High 36149942
2022 MST1 phosphorylates and activates p53, promoting neuronal apoptosis in Alzheimer's disease. MST1 overexpression in normal mice induces AD-like cognitive deficits, while p53 knockout largely reverses MST1-induced cognitive deficits. Genetic knockdown or chemical inactivation of MST1 improves cognitive function in 5xFAD mice. Co-IP (MST1-p53), in vivo MST1 overexpression and knockdown in mice, p53 KO epistasis, 5xFAD mouse model, XMU-MP-1 treatment Progress in neurobiology Medium 35525373
2022 SIRT7 suppresses MST1 expression by two mechanisms: (1) transcriptional repression by binding the MST1 promoter and inducing H3K18 deacetylation; (2) direct binding to and deacetylation of MST1 protein, which primes acetylation-dependent MST1 ubiquitination and proteasomal degradation. SIRT7 suppression of MST1 promotes YAP nuclear localization and HCC growth. ChIP assay (SIRT7 on MST1 promoter), co-IP (SIRT7-MST1), mass spectrometry (deacetylation sites), ubiquitination assay, HCC xenograft Cancer science High 38288904
2023 Mst1 phosphorylates the nuclear receptor Nur77 at Thr366, promoting Nur77 transcriptional activity and increasing downstream β3-integrin expression to enhance trophoblast-uterine epithelium adhesion and endometrial receptivity. Phospho-Nur77-T366 is decreased in women with recurrent implantation failure. In vitro kinase assay followed by LC-MS/MS for site identification, phos-tag SDS-PAGE, phospho-specific antibody, embryo adhesion assays, mouse delayed implantation model EBioMedicine High 36623453
2014 PCMT1 was identified as an MST1-interacting protein by yeast two-hybrid screening, confirmed by co-IP in HEK293 cells and cardiomyocytes. PCMT1 interacts with the kinase domain of MST1 (not the C-terminal regulatory domain). PCMT1 overexpression attenuates MST1 activation and apoptotic effects in cardiomyocytes subjected to hypoxia/reoxygenation. Yeast two-hybrid screen, co-IP (endogenous PCMT1-MST1), kinase domain mapping, hypoxia/reoxygenation cardiomyocyte model International journal of cardiology Medium 23647599
2014 MST1 forms a complex with cyclophilin D (Cyp-D) in mitochondria in response to gemcitabine-induced ROS, and this MST1/Cyp-D mitochondrial complex is required for gemcitabine-induced pancreatic cancer cell death. Cyclosporin A (Cyp-D inhibitor) prevents the MST1/Cyp-D mitochondrial complexation and cell death. Co-IP (MST1-CypD from mitochondrial fraction), mitochondrial translocation assay, MST1/CypD overexpression and shRNA, cyclosporin A pharmacological inhibition Biochimie Medium 24732633

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2012 Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 1377 22863277
2010 Network organization of the human autophagy system. Nature 1286 20562859
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
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2009 Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer cell 791 19878874
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2006 A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 713 16751106
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
2000 TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. The EMBO journal 635 11118213
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2005 The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene 499 15688006
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2010 The Hippo pathway regulates Wnt/beta-catenin signaling. Developmental cell 480 20412773
2010 Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proceedings of the National Academy of Sciences of the United States of America 473 20080598
2013 Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2. Nature medicine 450 24141421
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
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2003 Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. Cell 385 12757711
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2009 Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell 375 19596235
2008 MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Current biology : CB 357 18328708
1998 Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. The EMBO journal 331 9545236
2016 Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Science translational medicine 330 27535619
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2002 Identification of a novel Ras-regulated proapoptotic pathway. Current biology : CB 318 11864565
2004 Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. The Biochemical journal 303 15109305
2012 The phenotype of human STK4 deficiency. Blood 254 22294732
2015 Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity. Nature immunology 208 26414765
2014 MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes. Nature medicine 182 24633305
2002 Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation. The Journal of biological chemistry 164 12223493
2009 Regulation of neuronal cell death by MST1-FOXO1 signaling. The Journal of biological chemistry 160 19221179
2014 Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy. Molecular cell 156 25544559
2017 Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling. Journal of pineal research 151 28480597
2001 Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation. Proceedings of the National Academy of Sciences of the United States of America 147 11517310
2019 Quercetin Suppresses the Progression of Atherosclerosis by Regulating MST1-Mediated Autophagy in ox-LDL-Induced RAW264.7 Macrophage Foam Cells. International journal of molecular sciences 145 31816893
2012 The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. The Journal of experimental medicine 142 22412158
2009 Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes. The EMBO journal 140 19339990
2008 The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proceedings of the National Academy of Sciences of the United States of America 134 19073936
2014 Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL. Molecular cell 124 24813943
2007 The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1. The EMBO journal 118 17932490
2015 mTORC2 regulates cardiac response to stress by inhibiting MST1. Cell reports 116 25843706
2011 The c-Abl-MST1 signaling pathway mediates oxidative stress-induced neuronal cell death. The Journal of neuroscience : the official journal of the Society for Neuroscience 111 21715626
2015 STK4 regulates TLR pathways and protects against chronic inflammation-related hepatocellular carcinoma. The Journal of clinical investigation 109 26457732
2016 MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in mice. Diabetologia 107 27510910
2010 Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis. Molecular cell 107 20513427
2018 Mst1 promotes cardiac ischemia-reperfusion injury by inhibiting the ERK-CREB pathway and repressing FUNDC1-mediated mitophagy. The journal of physiological sciences : JPS 104 29961191
2014 MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through suppressing STK4 in vitro and in vivo. Oncogenesis 98 24752237
2018 Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R-STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity. Immunity 97 30413360
2010 Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development. British journal of cancer 92 21102585
2009 The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation. Current biology : CB 92 19836237
2022 MST1 mediates neuronal loss and cognitive deficits: A novel therapeutic target for Alzheimer's disease. Progress in neurobiology 84 35525373
2018 Mst1 inhibits Sirt3 expression and contributes to diabetic cardiomyopathy through inhibiting Parkin-dependent mitophagy. Biochimica et biophysica acta. Molecular basis of disease 81 29674007
2013 Mst1 and Mst2 kinases: regulations and diseases. Cell & bioscience 80 23985272
2016 MST1/MST2 Protein Kinases: Regulation and Physiologic Roles. Biochemistry 76 27618557
2019 A MST1-FOXO1 cascade establishes endothelial tip cell polarity and facilitates sprouting angiogenesis. Nature communications 74 30783090
2004 Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Oncogene 74 15007383
2017 Dendritic cell MST1 inhibits Th17 differentiation. Nature communications 71 28145433
2014 The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis. Nature communications 71 25367221
2016 Melatonin alleviates postinfarction cardiac remodeling and dysfunction by inhibiting Mst1. Journal of pineal research 70 27696525
2008 Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Mucosal immunology 69 19079170
2009 Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120. The Journal of biological chemistry 68 19940129
2015 STK4 (MST1) deficiency in two siblings with autoimmune cytopenias: A novel mutation. Clinical immunology (Orlando, Fla.) 66 26117625
2011 Identification of MST1/STK4 and SULF1 proteins as autoantibody targets for the diagnosis of colorectal cancer by using phage microarrays. Molecular & cellular proteomics : MCP 59 21228115
2020 MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer. PLoS pathogens 58 32555725
2018 Mst1 regulates post-infarction cardiac injury through the JNK-Drp1-mitochondrial fission pathway. Cellular & molecular biology letters 55 29760744
2015 A conserved MST1/2-YAP axis mediates Hippo signaling during lung growth. Developmental biology 53 25912685
2020 Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism. Hepatology international 52 33037981
2020 Tubule-Specific Mst1/2 Deficiency Induces CKD via YAP and Non-YAP Mechanisms. Journal of the American Society of Nephrology : JASN 50 32253273
2018 Melatonin Regulates Apoptosis and Autophagy Via ROS-MST1 Pathway in Subarachnoid Hemorrhage. Frontiers in molecular neuroscience 50 29632474
2019 FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2-dependent apoptosis. Cell death and differentiation 49 30903103
2021 STK3/STK4 signalling in adipocytes regulates mitophagy and energy expenditure. Nature metabolism 48 33758424
2014 Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway. Journal of neuro-oncology 48 25373346
2017 Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1. Biochemical and biophysical research communications 46 29127009
2013 Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. PloS one 46 24040101
2016 MST1: a promising therapeutic target to restore functional beta cell mass in diabetes. Diabetologia 45 27053234
2017 eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation. Biochimica et biophysica acta. Gene regulatory mechanisms 44 28487214
2010 MST1 limits the kinase activity of aurora B to promote stable kinetochore-microtubule attachment. Current biology : CB 43 20171103
2019 Structural insights into BCL2 pro-survival protein interactions with the key autophagy regulator BECN1 following phosphorylation by STK4/MST1. Autophagy 42 30626284
2014 Genetic deletion of Mst1 alters T cell function and protects against autoimmunity. PloS one 41 24852423
2020 Mst1 knockdown alleviates cardiac lipotoxicity and inhibits the development of diabetic cardiomyopathy in db/db mice. Biochimica et biophysica acta. Molecular basis of disease 40 32320827
2021 CCL2 regulation of MST1-mTOR-STAT1 signaling axis controls BCR signaling and B-cell differentiation. Cell death and differentiation 39 33879857
2020 Netrin1 deficiency activates MST1 via UNC5B receptor, promoting dopaminergic apoptosis in Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 39 32929029
2014 Gemcitabine-induced pancreatic cancer cell death is associated with MST1/cyclophilin D mitochondrial complexation. Biochimie 38 24732633
2022 MST1 Suppresses Disturbed Flow Induced Atherosclerosis. Circulation research 35 36164986
2018 EBV Negative Lymphoma and Autoimmune Lymphoproliferative Syndrome Like Phenotype Extend the Clinical Spectrum of Primary Immunodeficiency Caused by STK4 Deficiency. Frontiers in immunology 35 30386345
2014 Overexpression of MYC and EZH2 cooperates to epigenetically silence MST1 expression. Epigenetics 34 24499724
2020 LncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through Mst1. Cell cycle (Georgetown, Tex.) 31 32627655
2014 Constitutively active NDR1-PIF kinase functions independent of MST1 and hMOB1 signalling. Cellular signalling 30 24747552
2017 Understanding the role of mammalian sterile 20-like kinase 1 (MST1) in cardiovascular disorders. Journal of molecular and cellular cardiology 29 29155025
2024 SIRT7 promotes Hippo/YAP activation and cancer cell proliferation in hepatocellular carcinoma via suppressing MST1. Cancer science 28 38288904
2024 Inhibition of MST1 ameliorates neuronal apoptosis via GSK3β/β-TrCP/NRF2 pathway in spinal cord injury accompanied by diabetes. Redox biology 28 38430683
2018 Cardiac-specific Mst1 deficiency inhibits ROS-mediated JNK signalling to alleviate Ang II-induced cardiomyocyte apoptosis. Journal of cellular and molecular medicine 28 30338935
2017 TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 28802229
2022 METTL3-Induced miR-222-3p Upregulation Inhibits STK4 and Promotes the Malignant Behaviors of Thyroid Carcinoma Cells. The Journal of clinical endocrinology and metabolism 27 34562008
2017 Mapping the STK4/Hippo signaling network in prostate cancer cell. PloS one 26 28880957
2016 H-ras Inhibits the Hippo Pathway by Promoting Mst1/Mst2 Heterodimerization. Current biology : CB 26 27238285
2016 Mst1 positively regulates B-cell receptor signaling via CD19 transcriptional levels. Blood advances 26 29296937
2013 Protein-L-isoaspartate (D-aspartate) O-methyltransferase protects cardiomyocytes against hypoxia induced apoptosis through inhibiting proapoptotic kinase Mst1. International journal of cardiology 26 23647599
2020 Hippo kinases MST1 and MST2 control the differentiation of the epididymal initial segment via the MEK-ERK pathway. Cell death and differentiation 25 32332916
2016 Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis. Experimental cell research 25 27793648
2018 Mst1/2 Kinases Modulate Glucose Uptake for Osteoblast Differentiation and Bone Formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 24 29474739
2017 Rassf Proteins as Modulators of Mst1 Kinase Activity. Scientific reports 24 28327630
2022 A Stk4-Foxp3-NF-κB p65 transcriptional complex promotes Treg cell activation and homeostasis. Science immunology 23 36149942
2021 Deubiquitinating enzyme USP46 suppresses the progression of hepatocellular carcinoma by stabilizing MST1. Experimental cell research 23 34029571
2014 RASSF5 inhibits growth and invasion and induces apoptosis in osteosarcoma cells through activation of MST1/LATS1 signaling. Oncology reports 23 25109282
2018 Mst1 regulates non-small cell lung cancer A549 cell apoptosis by inducing mitochondrial damage via ROCK1/F‑actin pathways. International journal of oncology 22 30320378
2023 Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice. EBioMedicine 21 36623453
2020 MST1/2 Balance Immune Activation and Tolerance by Orchestrating Adhesion, Transcription, and Organelle Dynamics in Lymphocytes. Frontiers in immunology 21 32435241
2012 Tumor suppressor Hippo/MST1 kinase mediates chemotaxis by regulating spreading and adhesion. Proceedings of the National Academy of Sciences of the United States of America 21 22847424
2020 SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy. Aging 20 31951593
2020 Hippo Kinases MST1/2 Regulate Immune Cell Functions in Cancer, Infection, and Autoimmune Diseases. Critical reviews in eukaryotic gene expression 20 33389879
2014 Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. PloS one 20 25133611
2022 XMU-MP-1 protects heart from ischemia/reperfusion injury in mice through modulating Mst1/AMPK pathway. European journal of pharmacology 19 35123978
2018 The Role of Mst1 in Lymphocyte Homeostasis and Function. Frontiers in immunology 19 29459865
2023 miR-200a-3p overexpression alleviates diabetic cardiomyopathy injury in mice by regulating autophagy through the FOXO3/Mst1/Sirt3/AMPK axis. PeerJ 18 37727684
2018 MST1 down-regulation in decreasing apoptosis of aortic dissection smooth muscle cell apoptosis. European review for medical and pharmacological sciences 18 29687861
2014 Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. PloS one 18 24595170
2023 MST1/2 in inflammation and immunity. Cell adhesion & migration 17 37909712
2021 Downregulation of ROR2 promotes dental pulp stem cell senescence by inhibiting STK4-FOXO1/SMS1 axis in sphingomyelin biosynthesis. Aging cell 17 34278704
2020 TRAF6-mediated ubiquitination of MST1/STK4 attenuates the TLR4-NF-κB signaling pathway in macrophages. Cellular and molecular life sciences : CMLS 17 32975614
2020 STK4 Deficiency Impairs Innate Immunity and Interferon Production Through Negative Regulation of TBK1-IRF3 Signaling. Journal of clinical immunology 17 33078349