| 2004 |
YSK1 (STK25) targets to the Golgi apparatus via direct binding to the Golgi matrix protein GM130, and GM130 binding activates YSK1 by promoting autophosphorylation of a conserved threonine within the T-loop. A biochemical screen identified 14-3-3zeta as a specific substrate for YSK1 phosphorylation at the Golgi. Interference with YSK1 function perturbs perinuclear Golgi organization, cell migration, and invasion into type I collagen. |
Co-immunoprecipitation, in vitro kinase assays, biochemical substrate screen, dominant-negative interference, cell migration/invasion assays |
The Journal of cell biology |
High |
15037601
|
| 2010 |
Stk25 functions as part of an LKB1-Stk25-GM130 signaling pathway that regulates Golgi morphology and neuronal polarization. Overexpression of Stk25 induces Golgi condensation and multiple axons (supernumerary axons), both of which are rescued by Reelin treatment, placing STK25 in opposition to Reelin-Dab1 signaling. Reelin-Dab1 promotes extension of the Golgi into dendrites, which is suppressed by Stk25 overexpression. |
Overexpression and knockdown in cultured neurons, in vivo mouse genetics (Reelin and Dab1 mutants), Golgi morphology imaging, axon/dendrite quantification |
Cell |
High |
21111240
|
| 2011 |
MO25α/β isoforms directly bind to STK25/YSK1 (and MST3/MST4) and stimulate their kinase activity approximately 3- to 4-fold, in a manner analogous to how MO25 activates LKB1 via STRAD. |
Binding assays (surface plasmon resonance, co-immunoprecipitation), in vitro kinase activity assays with recombinant proteins, siRNA knockdown of MO25 in cells |
The EMBO journal |
High |
21423148
|
| 2008 |
SOK1 (STK25) regulates apoptotic cell death after chemical anoxia via the intrinsic apoptotic pathway. A caspase-cleaved form of SOK1 translocates from the Golgi to the nucleus after anoxia, dependent on caspase activity and on amino acids 275-292 C-terminal to the kinase domain. Nuclear entry of SOK1 is required for the cell death response, as SOK1 mutants unable to enter the nucleus do not induce cell death. |
RNA interference (siRNA knockdown), overexpression of wild-type and nuclear-localization mutants, subcellular fractionation/imaging, apoptosis assays, caspase inhibitor experiments |
The Journal of biological chemistry |
Medium |
18364353
|
| 1997 |
YSK1 (STK25) encodes a novel mammalian Ste20-related serine/threonine kinase with intrinsic protein kinase activity detectable by immunoprecipitation kinase assay. Overexpression of YSK1 does not activate the ERK, JNK/SAPK, or p38 MAPK pathways. |
cDNA cloning, immunoprecipitation kinase assay, overexpression with downstream MAPK pathway reporter assays |
Oncogene |
Medium |
9160885
|
| 2012 |
PDCD10 (CCM3) physically interacts with STK25, and co-expression of both proteins accelerates cell apoptosis under oxidative stress (H2O2). PDCD10 stabilizes STK25 protein through a proteasome-dependent pathway. PDCD10/STK25 interaction modulates ERK activity under oxidative stress. |
Co-immunoprecipitation, siRNA knockdown, overexpression, apoptosis assays, proteasome inhibitor experiments, ERK activity measurement |
Frontiers in bioscience (Landmark edition) |
Medium |
22652780
|
| 2012 |
STK25 physically interacts with CCM2 (cerebral cavernous malformation 2 protein) and can phosphorylate CCM2. STK25 is part of the TrkA-CCM2 death-signaling pathway in medulloblastoma cells: knockdown of STK25 (but not STK24) rescues cells from NGF-induced TrkA-dependent cell death, and the kinase activity of STK25 is required for death signaling. |
Affinity proteomics (AP-MS), co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, cell death assays, kinase-dead mutant |
The Journal of biological chemistry |
High |
22782892
|
| 2012 |
Stk25 knockdown in embryonic neurons reduces Tau phosphorylation. Stk25 regulates neuronal polarization and Golgi morphology in an antagonistic manner to Dab1 (Reelin pathway), as identified by microarray-based modifier screen in dab1-null mice and validated by knockdown. |
Microarray gene expression comparison between strains, siRNA knockdown in embryonic neurons, Tau phosphorylation assay, Golgi morphology imaging |
PloS one |
Medium |
22355340
|
| 2013 |
Partial depletion of STK25 in rat L6 myoblasts increases expression of Ucp3 and lipid oxidation, and enhances expression of Glut1, Glut4, and hexokinase 2, resulting in improved insulin-stimulated glucose uptake. STK25 thus negatively regulates lipid oxidation and glucose uptake in skeletal muscle cells. |
siRNA knockdown in L6 myoblasts, qRT-PCR, western blot, palmitate oxidation assay, glucose uptake assay |
Diabetologia |
Medium |
22391949
|
| 2013 |
Acute loss of Stk25 function (Cre-mediated conditional knockout or siRNA knockdown) disrupts neuronal migration in the developing cortex. Knockdown of LKB1, STRAD, and GM130 — molecules in the LKB1-STRAD-Stk25-GM130 pathway — causes similar neuronal migration errors. |
Conditional (Cre-mediated) knockout, siRNA knockdown, in utero electroporation, neuronal migration assays in developing mouse brain |
Neural development |
Medium |
24225308
|
| 2015 |
STK25 localizes to intrahepatic lipid droplets, colocalizing with the lipid droplet-coating protein ADFP/ATGL. STK25 overexpression reduces β-oxidation and triacylglycerol secretion in liver, promoting steatosis, while ATGL is displaced from the lipid droplet surface to the cytoplasm in STK25 transgenic livers. |
Transgenic mouse model (high-fat diet challenge), immunofluorescence colocalization, subcellular fractionation, β-oxidation assay, TAG secretion assay, western blot |
FASEB journal |
Medium |
25609431
|
| 2015 |
STK25 deficiency in knockout mice suppresses development of hyperglycemia, reduces hepatic gluconeogenesis, and increases insulin sensitivity. Stk25-/- mice show decreased protein levels of acetyl-CoA carboxylase (ACC), implicating ACC regulation as a mechanism underlying altered lipid oxidation and synthesis. |
Stk25 knockout mice on high-fat diet, glucose/insulin tolerance tests, euglycemic-hyperinsulinemic clamp, hepatic gene/protein expression analysis, western blot |
Diabetes |
Medium |
25845663
|
| 2019 |
STK25 activates LATS kinase by promoting LATS activation loop phosphorylation independently of prior hydrophobic motif phosphorylation, thereby activating Hippo signaling and suppressing YAP/TAZ transcriptional co-activators. Loss of STK25 promotes YAP/TAZ activation and enhanced cellular proliferation under growth-suppressive conditions. |
siRNA/CRISPR loss-of-function, phospho-specific antibody assays for LATS activation loop vs. hydrophobic motif, YAP/TAZ reporter assays, in vitro and in vivo proliferation assays, cancer genomics analysis |
Nature communications |
High |
30948712
|
| 2020 |
STK25 promotes STRIPAK-mediated inhibition of MST2 (Hippo pathway) by directly phosphorylating the scaffolding protein SAV1, which diminishes SAV1's ability to inhibit the STRIPAK phosphatase complex. Thus STK25, as the kinase component of STRIPAK, antagonizes SAV1 to suppress Hippo signaling initiation. |
siRNA depletion of STK25 in human cells, in vitro kinase assay (STK25 phosphorylating SAV1), co-immunoprecipitation assessing STRIPAK integrity, MST2 activation assays |
eLife |
High |
32292165
|
| 2018 |
STK25 interacts with GOLPH3 (Golgi phosphoprotein 3) and suppresses aerobic glycolysis in colorectal cancer cells through GOLPH3-regulated mTOR signaling, thereby inhibiting cell proliferation. |
Co-immunoprecipitation, GST pull-down, His-tag pull-down, western blot for mTOR pathway, glucose uptake and lactate production assays, xenograft mouse model |
Journal of experimental & clinical cancer research |
Medium |
29996891
|
| 2021 |
STK25 regulates neuronal migration and polarization by controlling Rho GTPase activities: STK25 promotes Rac1 activation and reduces RhoA levels in the developing brain through forming complexes with α-PIX and β-PIX (GTPase regulatory enzymes) and with Cullin3-Bacurd1/Kctd13 (a RhoA ubiquitination complex), in a kinase activity-independent manner. |
Stk25 conditional knockout, in utero electroporation, rescue experiments with MST3 overexpression, co-immunoprecipitation for complex formation, RhoA/Rac1 activity assays, overexpression of Bacurd1/Cul3 |
The Journal of neuroscience |
Medium |
34518307
|
| 2022 |
STK25 phosphorylates the type Iα regulatory subunit of PKA (PRKAR1A), which leads to inhibition of PKA catalytic activity and increased binding of the regulatory subunit to the catalytic subunit in the presence of cAMP. In Stk25 knockout mice, PRKAR1A phosphorylation is diminished, PKA activity is increased, and contractile response to beta-adrenergic stimulation is augmented. |
iPSC-derived cardiomyocytes, in vitro kinase assay, co-immunoprecipitation (regulatory-catalytic subunit binding), Stk25 knockout mouse model, PKA activity assay, cardiac contractility measurements |
Cell reports |
High |
35977512
|
| 2022 |
STK25 deficiency in mice and human endothelial cells causes KLF2 expression, Golgi dispersion, altered β-catenin distribution, and stress fiber appearance. Combined deficiency of STK24 and STK25 (but not either alone) in mice causes aggressive cavernoma-like vascular lesions, and STK25 deficiency alone induces these phenotypes in the context of STK24 heterozygosity. |
Double Stk24/Stk25 knockout mice, siRNA in human endothelial cells, histology, immunofluorescence for KLF2/β-catenin/stress fibers/Golgi morphology |
Stroke |
Medium |
35130716
|
| 2022 |
STK25 deficiency increases PD-L1 protein stability by regulating K48-linked ubiquitination of PD-L1 in a NEDD4-dependent manner, thereby increasing PD-L1 surface levels and modulating tumor immune evasion in colorectal cancer. |
STK25 knockout cell lines and mice, co-immunoprecipitation, ubiquitination assays (K48-linkage specific), western blot for PD-L1 protein levels, in vivo tumor models with anti-PD-1 treatment |
Advanced science |
Medium |
40729594
|
| 2025 |
STK25 undergoes autophosphorylation in response to multiple TLR triggers and phosphorylates IRF5 at Thr265, leading to IRF5 transcriptional activation and pro-inflammatory cytokine production. Loss of STK25 in primary immune cells attenuates R848-induced IRF5 nuclear translocation and pro-inflammatory cytokine production. |
Kinome-wide siRNA screen in THP-1 cells, in vitro kinase assay (STK25 phosphorylating IRF5-Thr265), Stk25-deficient primary immune cells, IRF5 nuclear translocation assay, cytokine ELISA |
Life science alliance |
Medium |
40639948
|
| 2019 |
STK25 coats intrahepatic lipid droplets and regulates their associated phosphoproteome; STK25 deficiency in the liver alters proteins involved in peroxisomal biogenesis, ubiquitination-mediated proteolysis, and antioxidant defense. STK25 silencing in human liver cells attenuates peroxisomal biogenesis and protects against oxidative and ER stress in a hepatocyte-autonomous manner. |
Stk25 knockout mice (high-fat diet), quantitative lipid droplet-associated phosphoproteomics, peroxisomal biogenesis assays, oxidative/ER stress markers in human liver cells with STK25 siRNA |
Journal of lipid research |
Medium |
31857389
|
| 2026 |
STK25 deficiency in colorectal cancer cells activates the NF-κB pathway, leading to p50 phosphorylation that directly binds the AREG promoter and transcriptionally upregulates AREG expression; elevated AREG then activates EGFR on cancer-associated fibroblasts (CAFs), promoting CAF activation and cetuximab resistance. |
siRNA knockdown and overexpression in CRC cells, ChIP assay (p50 binding to AREG promoter), dual-luciferase reporter assay, CAF co-culture, in vivo xenograft models, patient-derived organoids |
Clinical and translational medicine |
Medium |
42057436
|