MST1/2 in Inflammation and Immunity

Overview

Journal Cell Adh Migr

Specialty Cell Biology

Date 2023 Nov 1

PMID 37909712

Authors

Tongfen Li

Yiqiong Wen

Qiongfen Lu

Shu Hua

Yunjiao Hou

Xiaohua Du

Yuanyuan Zheng

Shibo Sun

Affiliations

Soon will be listed here.

Abstract

The mammalian Sterile 20-like kinase 1/2 (MST1/2) belongs to the serine/threonine (GC) protein kinase superfamily. Collective studies confirm the vital role MST1/2 in inflammation and immunity. MST1/2 is closely related to the progress of inflammation. Generally, MST1/2 aggravates the inflammatory injury through MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB pathways, as well as several regulatory factors such as tumor necrosis factor-α (TNF-α), mitochondrial extension factor 1 (MIEF1), and lipopolysaccharide (LPS). Moreover, MST1/2 is also involved in the regulation of immunity to balance immune activation and tolerance by regulating MST1/2-Rac, MST1-Akt1/c-myc, MST1-Foxos, MST1-STAT, Btk pathways, and lymphocyte function-related antigen 1 (LFA-1), which subsequently prevents immunodeficiency syndrome and autoimmune diseases. This article reviews the effects of MST1/2 on inflammation and immunity.

Citing Articles

STAT6 deficiency mitigates the severity of pulmonary arterial hypertension caused by chronic intermittent hypoxia by suppressing Th2-inducing cytokines.

Jiang P, Huang H, Liu Z, Xiang G, Wu X, Hao S Respir Res. 2025; 26(1):13.

PMID: 39806384 PMC: 11731530. DOI: 10.1186/s12931-024-03062-z.

Shared genetic architecture and bidirectional clinical risks within the psycho-metabolic nexus.

Guo X, Feng Y, Ji X, Jia N, Maimaiti A, Lai J EBioMedicine. 2024; 111():105530.

PMID: 39731856 PMC: 11743124. DOI: 10.1016/j.ebiom.2024.105530.

MST1, a novel therapeutic target for Alzheimer's disease, regulates mitochondrial homeostasis by mediating mitochondrial DNA transcription and the PI3K-Akt-ROS pathway.

Cui D, Liu H, Cao L, Du X, Liu D, Liu Z J Transl Med. 2024; 22(1):1056.

PMID: 39578795 PMC: 11583452. DOI: 10.1186/s12967-024-05852-x.

Polymorphism rs3197999 in Pediatric Patients with Inflammatory Bowel Disease.

Brylak J, Nowak J, Dybska E, Glapa-Nowak A, Kierkus J, Osiecki M Medicina (Kaunas). 2024; 60(8).

PMID: 39202524 PMC: 11356727. DOI: 10.3390/medicina60081243.

Amphiregulin orchestrates the paracrine immune-suppressive function of amniotic-derived cells through its interplay with COX-2/PGE/EP4 axis.

Prencipe G, Cervero-Varona A, Perugini M, Sulcanese L, Iannetta A, Haidar-Montes A iScience. 2024; 27(8):110508.

PMID: 39156643 PMC: 11326934. DOI: 10.1016/j.isci.2024.110508.

References

Bagherzadeh Yazdchi S, Witalis M, Meli A, Leung J, Li X, Panneton V . Hippo Pathway Kinase Mst1 Is Required for Long-Lived Humoral Immunity. J Immunol. 2018; 202(1):69-78. PMC: 6310088. DOI: 10.4049/jimmunol.1701407. View

Du X, Wen J, Wang Y, Karmaus P, Khatamian A, Tan H . Hippo/Mst signalling couples metabolic state and immune function of CD8α dendritic cells. Nature. 2018; 558(7708):141-145. PMC: 6292204. DOI: 10.1038/s41586-018-0177-0. View

Chi Q, Hu X, Liu Z, Han Y, Tao D, Xu S . HS exposure induces cell death in the broiler thymus via the ROS-initiated JNK/MST1/FOXO1 pathway. Ecotoxicol Environ Saf. 2021; 222:112488. DOI: 10.1016/j.ecoenv.2021.112488. View

Ouyang H, Li Q, Zhong J, Xia F, Zheng S, Lu J . Combination of melatonin and irisin ameliorates lipopolysaccharide-induced cardiac dysfunction through suppressing the Mst1-JNK pathways. J Cell Physiol. 2020; 235(10):6647-6659. DOI: 10.1002/jcp.29561. View

Manning G, Whyte D, Martinez R, Hunter T, Sudarsanam S . The protein kinase complement of the human genome. Science. 2002; 298(5600):1912-34. DOI: 10.1126/science.1075762. View

Lu J, Hu Z, Deng Y, Wu Q, Wu M, Song H . MEKK2 and MEKK3 orchestrate multiple signals to regulate Hippo pathway. J Biol Chem. 2021; 296:100400. PMC: 7948509. DOI: 10.1016/j.jbc.2021.100400. View

Abdollahpour H, Appaswamy G, Kotlarz D, Diestelhorst J, Beier R, Schaffer A . The phenotype of human STK4 deficiency. Blood. 2012; 119(15):3450-7. PMC: 3325036. DOI: 10.1182/blood-2011-09-378158. View

Shang X, Zhang Y, Xu J, Li M, Wang X, Yu R . SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy. Aging (Albany NY). 2020; 12(2):1417-1432. PMC: 7053598. DOI: 10.18632/aging.102691. View

Li J, Du X, Shi H, Deng K, Chi H, Tao W . Mammalian Sterile 20-like Kinase 1 (Mst1) Enhances the Stability of Forkhead Box P3 (Foxp3) and the Function of Regulatory T Cells by Modulating Foxp3 Acetylation. J Biol Chem. 2015; 290(52):30762-70. PMC: 4692206. DOI: 10.1074/jbc.M115.668442. View

10.

Wang A, Wang J, Wu J, Deng X, Zou Y . Suramin protects hepatocytes from LPS-induced apoptosis by regulating mitochondrial stress and inactivating the JNK-Mst1 signaling pathway. J Physiol Sci. 2019; 69(3):489-502. PMC: 10717776. DOI: 10.1007/s12576-019-00666-9. View

11.

Chen L . Non-canonical Hippo signaling regulates immune responses. Adv Immunol. 2019; 144:87-119. DOI: 10.1016/bs.ai.2019.07.001. View

12.

Koehler T, Tran T, Weingartner K, Kavran J . Kinetic Regulation of the Mammalian Sterile 20-like Kinase 2 (MST2). Biochemistry. 2022; 61(16):1683-1693. PMC: 10167949. DOI: 10.1021/acs.biochem.2c00022. View

13.

Kondo N, Ueda Y, Kita T, Ozawa M, Tomiyama T, Yasuda K . NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization. Mol Cell Biol. 2017; 37(8). PMC: 5376635. DOI: 10.1128/MCB.00424-16. View

14.

Shi H, Liu C, Tan H, Li Y, Nguyen T, Dhungana Y . Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R-STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity. Immunity. 2018; 49(5):899-914.e6. PMC: 6249059. DOI: 10.1016/j.immuni.2018.10.010. View

15.

Shang X, Li J, Yu R, Zhu P, Zhang Y, Xu J . Sepsis-related myocardial injury is associated with Mst1 upregulation, mitochondrial dysfunction and the Drp1/F-actin signaling pathway. J Mol Histol. 2019; 50(2):91-103. DOI: 10.1007/s10735-018-09809-5. View

16.

Malek T, Castro I . Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity. 2010; 33(2):153-65. PMC: 2946796. DOI: 10.1016/j.immuni.2010.08.004. View

17.

Li C, Bi Y, Li Y, Yang H, Yu Q, Wang J . Dendritic cell MST1 inhibits Th17 differentiation. Nat Commun. 2017; 8:14275. PMC: 5296641. DOI: 10.1038/ncomms14275. View

18.

Randriamboavonjy V, Kyselova A, Elgheznawy A, Zukunft S, Wittig I, Fleming I . Calpain 1 cleaves and inactivates prostacyclin synthase in mesenteric arteries from diabetic mice. Basic Res Cardiol. 2016; 112(1):10. DOI: 10.1007/s00395-016-0596-8. View

19.

Cho K, Kim M, Jung H, Choi E, Kim T . Mst1-Deficiency Induces Hyperactivation of Monocyte-Derived Dendritic Cells via Akt1/c-myc Pathway. Front Immunol. 2019; 10:2142. PMC: 6749027. DOI: 10.3389/fimmu.2019.02142. View

20.

Fukuhara T, Tomiyama T, Yasuda K, Ueda Y, Ozaki Y, Son Y . Hypermethylation of MST1 in IgG4-related autoimmune pancreatitis and rheumatoid arthritis. Biochem Biophys Res Commun. 2015; 463(4):968-74. DOI: 10.1016/j.bbrc.2015.06.043. View