製品: Phospho-MST1(Thr183)/MST2(Thr180) Antibody
カタログ: AF2367
タンパク質の説明: Rabbit polyclonal antibody to Phospho-MST1(Thr183)/MST2(Thr180)
アプリケーション: WB IHC IF/ICC
Cited expt.: WB, IHC
反応性: Human, Mouse, Rat
予測: Pig, Zebrafish, Bovine, Horse, Sheep, Rabbit, Dog, Chicken, Xenopus
分子量: 59kDa; 56kD(Calculated).
ユニプロット: Q13043 | Q13188
RRID: AB_2845381

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製品説明

ソース:
Rabbit
アプリケーション:
IF/ICC 1:100-1:500, WB 1:500-1:2000, IHC 1:50-1:200
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human,Mouse,Rat
予測:
Pig(100%), Zebrafish(100%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%), Xenopus(100%)
クローナリティ:
Polyclonal
特異性:
Phospho-MST1(Thr183)/MST2(Thr180) Antibody detects endogenous levels of MST1 onlyPhospho-MST1 (Thr183/Thr180) Antibody detects endogenous levels of MST1 when phosphorylated at Thr183 or MST2 when phosphorylated at Thr180.
RRID:
AB_2845381
引用形式: Affinity Biosciences Cat# AF2367, RRID:AB_2845381.
コンジュゲート:
Unconjugated.
精製:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ/展開

Kinase responsive to stress; Krs2; Mammalian STE20 like protein kinase 1; Mammalian STE20-like protein kinase 1; Mammalian sterile 20 like 1; MST-1; MST1; Serine/threonine kinase 4; Serine/threonine protein kinase Krs 2; Serine/threonine-protein kinase 4; Serine/threonine-protein kinase Krs-2; STE20 like kinase MST1; STE20-like kinase MST1; STK4; STK4_HUMAN; TIIAC; YSK3; 0610042I06Rik; EC 2.7.11.1; FLJ90748; KB 1458E12.1; Kinase responsive to stress 1; KRS1; Mammalian STE20 like protein kinase 2; Mammalian STE20-like protein kinase 2; Mammalian sterile 20-like 2; Mess1; MST; MST-2; MST2; Mst3; Serine/threonine kinase 3 (STE20 homolog, yeast); Serine/threonine kinase 3 (Ste20, yeast homolog); Serine/threonine kinase 3; Serine/threonine protein kinase 3; Serine/threonine protein kinase Krs1; Serine/threonine-protein kinase 3; Serine/threonine-protein kinase Krs-1; STE20 like kinase MST2; STE20-like kinase MST2; Stk3; STK3_HUMAN; wu:fc19e11; zgc:55383;

免疫原

免疫原:

A synthesized peptide derived from human MST1 around the phosphorylation site of Thr183.

Uniprot:
遺伝子(ID):
発現特異性:
Q13043 STK4_HUMAN:

Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed.

Q13188 STK3_HUMAN:

Expressed at high levels in adult kidney, skeletal and placenta tissues and at very low levels in adult heart, lung and brain tissues.

タンパク質配列:
METVQLRNPPRRQLKKLDEDSLTKQPEEVFDVLEKLGEGSYGSVYKAIHKETGQIVAIKQVPVESDLQEIIKEISIMQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDNFTDFVKQCLVKSPEQRATATQLLQHPFVRSAKGVSILRDLINEAMDVKLKRQESQQREVDQDDEENSEEDEMDSGTMVRAVGDEMGTVRVASTMTDGANTMIEHDDTLPSQLGTMVINAEDEEEEGTMKRRDETMQPAKPSFLEYFEQKEKENQINSFGKSVPGPLKNSSDWKIPQDGDYEFLKSWTVEDLQKRLLALDPMMEQEIEEIRQKYQSKRQPILDAIEAKKRRQQNF

MEQPPAPKSKLKKLSEDSLTKQPEEVFDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPVESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLIEDEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKKCLVKNPEQRATATQLLQHPFIKNAKPVSILRDLITEAMEIKAKRHEEQQRELEEEEENSDEDELDSHTMVKTSVESVGTMRATSTMSEGAQTMIEHNSTMLESDLGTMVINSEDEEEEDGTMKRNATSPQVQRPSFMDYFDKQDFKNKSHENCNQNMHEPFPMSKNVFPDNWKVPQDGDFDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDAMDAKKRRQQNF

種類予測

種類予測:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
100
Horse
100
Bovine
100
Sheep
100
Dog
100
Xenopus
100
Zebrafish
100
Chicken
100
Rabbit
100
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

研究背景

機能:

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.

PTMs:

Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-387 by PKB/AKT1, leads to inhibition of its: kinase activity, nuclear translocation and autophosphorylation at Thr-183. It also diminishes its cleavage by caspases and its ability to phosphorylate FOXO3.

Proteolytically cleaved by caspase-3 during apoptosis at Asp-326 and Asp-349 resulting in a 37 kDa or a 39 kDa subunit respectively. The 39 kDa subunit is further cleaved into the 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). It is less likely that cleavage at Asp-349 is a prerequisite for activation as this site is not conserved in the murine ortholog.

細胞の位置付け:

Cytoplasm. Nucleus.
Note: The caspase-cleaved form cycles between the nucleus and cytoplasm.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed.

タンパク質ファミリー:

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

機能:

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38.

PTMs:

Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1.

Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N).

細胞の位置付け:

Cytoplasm. Nucleus.
Note: The caspase-cleaved form cycles between nucleus and cytoplasm (By similarity). Phosphorylation at Thr-117 leads to inhibition of nuclear translocation.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

Expressed at high levels in adult kidney, skeletal and placenta tissues and at very low levels in adult heart, lung and brain tissues.

タンパク質ファミリー:

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

研究領域

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Ras signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > FoxO signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Hippo signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Hippo signaling pathway - multiple species.   (View pathway)

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Non-small cell lung cancer.   (View pathway)

参考文献

1). MST2 methylation by PRMT5 inhibits Hippo signaling and promotes pancreatic cancer progression. The EMBO journal, 2023 (PubMed: 37905571) [IF=9.4]

Application: WB    Species: Mouse    Sample: pancreatic cancer

Figure 7 PRMT5 and MST2‐SDMA are elevated but pMST2‐Thr180 is reduced in PDAC, and GSK3326595 suppresses the progression of pancreatic cancer A, B The representative IHC images of PRMT5, α‐me2s and pMST2‐Thr180 proteins on TMA (n = 37) of pancreatic cancer specimens were shown (A). Scale bars were indicated in the figure. The heatmap showed IHC score of PRMT5, α‐me2s and pMST2‐Thr180 proteins on TMA (n = 37) of pancreatic cancer specimens (B). C Twelve pairs of pancreatic cancer tissues and their matched para‐carcinoma tissues were extracted proteins. MST2 was immunopurified to compare the level of α‐me2s and phospho‐Thr180 between cancer tissues and para‐carcinoma tissues. Relative ratio was quantified and normalized to MST2. The level of PRMT5 and total α‐me2s was also compared. Immunoblotting was repeated technically three times independently. N = 12 biological replicates. D Relative α‐me2s level of MST2, relative pMST2‐Thr180 level of MST2, relative PRMT5 level, and relative total α‐me2s level of pancreatic cancer tissues and para‐carcinoma tissues were quantified and shown as the violin plots. The statistical significance was tested by the paired t‐test. Immunoblotting was repeated technically three times independently. N = 12 biological replicates. **P 

Application: IHC    Species: Mouse    Sample: pancreatic cancer

Figure 7 PRMT5 and MST2‐SDMA are elevated but pMST2‐Thr180 is reduced in PDAC, and GSK3326595 suppresses the progression of pancreatic cancer A, B The representative IHC images of PRMT5, α‐me2s and pMST2‐Thr180 proteins on TMA (n = 37) of pancreatic cancer specimens were shown (A). Scale bars were indicated in the figure. The heatmap showed IHC score of PRMT5, α‐me2s and pMST2‐Thr180 proteins on TMA (n = 37) of pancreatic cancer specimens (B). C Twelve pairs of pancreatic cancer tissues and their matched para‐carcinoma tissues were extracted proteins. MST2 was immunopurified to compare the level of α‐me2s and phospho‐Thr180 between cancer tissues and para‐carcinoma tissues. Relative ratio was quantified and normalized to MST2. The level of PRMT5 and total α‐me2s was also compared. Immunoblotting was repeated technically three times independently. N = 12 biological replicates. D Relative α‐me2s level of MST2, relative pMST2‐Thr180 level of MST2, relative PRMT5 level, and relative total α‐me2s level of pancreatic cancer tissues and para‐carcinoma tissues were quantified and shown as the violin plots. The statistical significance was tested by the paired t‐test. Immunoblotting was repeated technically three times independently. N = 12 biological replicates. **P 

2). Activation of MST1 protects filtration barrier integrity of diabetic kidney disease in mice through restoring the tight junctions of glomerular endothelial cells. Acta pharmacologica Sinica, 2024 (PubMed: 39643641) [IF=8.2]

3). Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-β/Smad and YAP signaling. PHYTOMEDICINE, 2020 (PubMed: 32771890) [IF=6.7]

Application: WB    Species: human    Sample: LX-2 cells

Fig. 6.| PD inhibits liver fibrosis through regulation of Hippo pathway. (A) LX-2 cells were treated with PD (5 μM, 10 μM, 20 μM) for 24 h with or without TGF-β1(5 ng/ml). Western blot analysis of Hippo signaling core factor protein expression.

4). Resveratrol Inhibits the Tumorigenesis of Follicular Thyroid Cancer via ST6GAL2-Regulated Activation of the Hippo Signaling Pathway. Molecular Therapy-Oncolytics, 2020 (PubMed: 32055676) [IF=5.3]

Application: WB    Species: human    Sample: FTC238 cells

Figure 6. |Res Reduces ST6GAL2 Expression and Activates the Hippo Signaling Pathway in FTC Cells(A–D) The qPCR and western blotting results indicated that ST6GAL2 expression changes after Res treatment in FTC cells. (E–G) Expression of the main protein components of the Hippo signaling pathway in FTC238 cells was assessed by western blotting. Also shown is western blot analysis of nuclear YAP and TAZ expression in the indicated cells. The nuclear protein histone H3 was used as the nuclear protein marker

5). Targeting mechanosensitive Piezo1 alleviated renal fibrosis through p38MAPK-YAP pathway. Frontiers in Cell and Developmental Biology, 2021 (PubMed: 34805150) [IF=4.6]

6). Salvianolic acid B exerts an anti-hepatocellular carcinoma effect by regulating the Hippo/YAP pathway and promoting pSmad3L to pSmad3C simultaneously. European Journal of Pharmacology, 2023 (PubMed: 36509132) [IF=4.2]

7). Tat-SynGAP improves angiogenesis and post-stroke recovery by inhibiting MST1/JNK signaling. Brain Research Bulletin, 2022 (PubMed: 34990733) [IF=3.5]

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