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Aging and disease    2018, Vol. 9 Issue (3) : 537-552     DOI: 10.14336/AD.2017.0702
Review Article |
Mammalian Sterile20-like Kinases: Signalings and Roles in Central Nervous System
Chen Sheng1,*, Fang Yuanjian1, Xu Shenbin1, Reis Cesar2,3, Zhang Jianmin1,4,*
1Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
2Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, USA.
3Brain Research Institute, Zhejiang University, Hangzhou, Zhejiang, China.
4Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, China.
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Abstract  

Mammalian Sterile20-like (MST) kinases are located upstream in the mitogen-activated protein kinase pathway, and play an important role in cell proliferation, differentiation, renewal, polarization and migration. Generally, five MST kinases exist in mammalian signal transduction pathways, including MST1, MST2, MST3, MST4 and YSK1. The central nervous system (CNS) is a sophisticated entity that takes charge of information reception, integration and response. Recently, accumulating evidence proposes that MST kinases are critical in the development of disease in different systems involving the CNS. In this review, we summarized the signal transduction pathways and interacting proteins of MST kinases. The potential biological function of each MST kinase and the commonly reported MST-related diseases in the neural system are also reviewed. Further investigation of MST kinases and their interaction with CNS diseases would provide the medical community with new therapeutic targets for human diseases.

Keywords Mammalian Sterile20-like kinases      central nervous system disorders      mitogen-activated protein kinase     
Corresponding Authors: Chen Sheng,Zhang Jianmin   
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These authors contributed equally to this work.

Issue Date: 05 June 2018
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Chen Sheng
Fang Yuanjian
Xu Shenbin
Reis Cesar
Zhang Jianmin
Cite this article:   
Chen Sheng,Fang Yuanjian,Xu Shenbin, et al. Mammalian Sterile20-like Kinases: Signalings and Roles in Central Nervous System[J]. Aging and disease, 2018, 9(3): 537-552.
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http://www.aginganddisease.org/EN/10.14336/AD.2017.0702     OR     http://www.aginganddisease.org/EN/Y2018/V9/I3/537
Figure 1.  Signaling network of MST1 and MST2 kinase. The signaling pathways of MST1/2 mainly include MST1/2-YAP/TAZ signaling pathway and MST1/2-FOXO signaling pathway. MST1/2 phosphorylates the downstream Lats1/2 and subsequently inhibits the transcriptional function of intranuclear YAP/TAZ, avoiding the excessive cell proliferation and organ overgrowth. The MST1/2 can also mediate this signaling pathway by suppressing GABA function. The MST1/2-FOXO signaling pathway mainly regulates the apoptosis process. MST1/2 phosphorylates AKT and subsequently disrupts its function of interaction between FOXO3 with 14-3-3 proteins. This indirectly promotes apoptosis process. In addition, Mst1 promotes the proapoptotic mediator NOXA transcription via the assistance of FOXO1. The MST1-induced JNK activation can also promote apoptosis. Several interacting partners such as RASSF members, DAP4, acinus and Raf-1 also combine with the MST1/2 and perform different biological functions.
Figure 2.  Signaling network of MST3, MST4 and YSK1 kinase. MST3, MST4 and YSK1 located on the Golgi apparatus with the assistance of GM130 and Striatin proteins. Unlike MST3 and MST4, YSK1 acts a positive role when localized to the Golgi via interaction with 14-3-3. This link potentially mediates the protein transport, cell polarity and cell adhesion. CCM3 or Mo25 induces the movement of MST3 and MST4 from the Golgi apparatus to the plasma membrane. Activated MST3/4 can promote co-localization of the actomyosin with help of Ezrin. Besides, MST3 inhibit PTP-PEST and prevent PTP-PEST dependent paxillin phosphorylation which consequently attenuates the cell migration. MST3 also can activate the NDR protein kinases to regulate the apoptosis process.
Figure 3.  Regulators of MST1 and MST2. Several regulators are involved in the MST1/2 signaling pathway. AMOT2 protein may potentially activate the Hippo-YAP pathway by sensing the mechanical alteration from the cell-cell junction. With the assistance GPCR, biological activation mediate Lats1/2 function in different circumstances. In addition, the SAV1/WW45 and RASSF can activate the MST1/2 through the interaction with SARAH domain. Caspase proteins from apoptotic processes can cleave the MST1/2 and promote human Hippo pathway. While PP2A, STRIPAK complex and TAO may own the potential effect on this pathway.
Figure 4.  Regulators of MST3 and MST4 and YSK1. The biological function of MST3, MST4 and YSK1 kinases mainly depend on the interaction with GM130, Mo25 and CCM3 binding proteins. Caspase proteins from apoptosis, PP2A and STRIPAK complex also can regulate MST3 or MST4.
Author/YearMST kinaseSignaling pathwayMain function
Lehtinenet al.[36]/2006MST1MST1-FOXO3Mediates oxidative-stress-induced cell death
Yuan et al.[22]/2009MST1MST1-FOXO1Mediates survival factor deprivation-induced cell death
Xiao et al.[67]/2011MST1c-Abl-MST1-FOXO3Mediates oxidative-stress-induced cell death
Yun et al.[70]/2011MST1IFN-γ-Daxx-MST1Mediates proinflammatory-cytokine-induced cell death
Lee et al.[68]/2014MST1MT3-zin-c-Abl-MST1Mediates oxidative-stress-induced cell death
Liu et al.[25]/2012MST2c-Abl-MST2Mediates oxidative-stress-induced cell death
Tang et al.[71]/2014MST3Cdk-5-MST3-RhoAMediates RhoA-dependent actin dynamics and neuronal migration
Ultanir et al.[48]/2014MST3MST3-TAO1/2Promotes spine synapse development
Zhou et al.[24]/2000MST3bPKA-MST3bMediates MAPK pathways
Irwin et al.[72]/2006MST3bNeurotrophic-MST3bPromotes axon outgrowth
Lorber et al.[14]/2009MST3b/Promotes axon regeneration
Fidalgo et al.[74]/2012MST4MST4-ERMPrevents oxidative-stress-induced cell death
Matsuki et al.[77]/2010STK25LKB1-STK25-GM130Mediates Golgi dispersion, axon specification and dendrite growth
Zhang et al.[76]/2012STK25CCM3—STK25Promotes oxidative-stress-induced cell apoptosis
Matsuki et al.[79]/2013STK25/Acute inactivation of STK25 instead of constitutive STK25 deficiency disrupts the neuronal migration
Table 1  Main findings of MST kinases in CNS biological function.
Author/yearDiseaseMST kinaseMain finding
TumorCosta et al.[99]
/2012
MedulloblastomaSTK25STK25 prevents medulloblastoma cells death via attenuating TrkA—STK25 signaling pathway
Chao et al. [97]
/2015
GlioblastomaMST1Mst1 prevents glioblastoma growth via attenuating AKT—mTOR signaling pathway
Zhu et al.[91]
/2015
GlioblastomaMST1/2miR-130b promotes glioblastoma growth via attenuating MST1/2—Lats—YAP/TAZ signaling pathway
Zhang et al.[88]
/2016
GlioblastomaMST1/2YAP/TAZ—BIRC5 signaling pathway induced by Lats down-regulation promotes glioblastoma growth
Vascular diseasesVoss et al.[106]
/2007
CCMSTK25Interaction between CCM2, CCM3 and STK25 mediates vascular development and CCM pathogenesis
Zheng et al.[104]
/2010
CCMSTK24/25Interaction between CCMs and STKs mediates vascular development and CCM pathogenesis
Zhao et al.[108]
/2016
Cerebral ischemiaMST1MST1 promotes cerebral-ischemia-induced microglia activation via Src—MST1—IκBα signaling pathway
Weng et al.[112]
/2016
Cerebral ischemiaMST1Malibatol A prevents cerebral-ischemia-induced microglia activation via c-Abl—MST1 signaling pathway
Yang et al.[115]
/2016
VDMST1TSL protects neurons activity in VD via attenuating inflammatory reaction mediated by MST1—FOXO3 signaling pathway
Neurodegenerative diseasesMatsuki et al.[23]
/2012
ADSTK25Stk25 attenuating AD development via preventing Tau phosphorylation induced by Dab1 deficiency
Lee et al.[130]
/2013
ALSMST1MST1 mediates ALS development via interaction with SOD1
Pan et al.[138]/2014Prion diseasesMST1c-Abl—MST1 signaling pathway promotes prion-induced neuralapoptosisin Prion diseases
Other CNS diseasesZhang et al.[142]/2015Spine injuryMST3bMst3b promotes neural regeneration in injured spinal cord
Imitola et al.[13]/20152q37 microdeletion syndromeSTK25STK25 deletion was the most interacting gene in neural development disorder of 2q37 microdeletion syndrome
Table 2  The MST kinases in CNS diseases.
[1] Seger R, Krebs EG (1995). The MAPK signaling cascade. FASEB J, 9: 726-735
[2] Lee Y, Kim YJ, Kim MH, Kwak JM (2016). MAPK Cascades in Guard Cell Signal Transduction. Front Plant Sci, 7: 80
[3] Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002). The protein kinase complement of the human genome. Science, 298: 1912-1934
[4] Ramer SW, Davis RW (1993). A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A, 90: 452-456
[5] Hofmann C, Shepelev M, Chernoff J (2004). The genetics of Pak. J Cell Sci, 117: 4343-4354
[6] Strange K, Denton J, Nehrke K (2006). Ste20-type kinases: evolutionarily conserved regulators of ion transport and cell volume. Physiology (Bethesda), 21: 61-68
[7] Ling P, Lu TJ, Yuan CJ, Lai MD (2008). Biosignaling of mammalian Ste20-related kinases. Cell Signal, 20: 1237-1247
[8] Pan D (2010). The hippo signaling pathway in development and cancer. Dev Cell, 19: 491-505
[9] Varelas X (2014). The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development, 141: 1614-1626
[10] Yu FX, Zhao B, Guan KL (2015). Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. Cell, 163: 811-828
[11] Preisinger C, Short B, De Corte V, Bruyneel E, Haas A, Kopajtich R, et al. (2004). YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3zeta. J Cell Biol, 164: 1009-1020
[12] Fitch MT, Silver J (2008). CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp Neurol, 209: 294-301
[13] Imitola J, Khurana DS, Teplyuk NM, Zucker M, Jethva R, Legido A, et al. (2015). A novel 2q37 microdeletion containing human neural progenitors genes including STK25 results in severe developmental delay, epilepsy, and microcephaly. Am J Med Genet A, 167A: 2808-2816
[14] Lorber B, Howe ML, Benowitz LI, Irwin N (2009). Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways. Nat Neurosci, 12: 1407-1414
[15] Tam RY, Fuehrmann T, Mitrousis N, Shoichet MS (2014). Regenerative therapies for central nervous system diseases: a biomaterials approach. Neuropsychopharmacology, 39: 169-188
[16] Bramlett HM (2013). Special issue of translational stroke: importance of sex in the pathophysiology and treatment of acute CNS repair. Transl Stroke Res, 4: 379-380
[17] Zhou D, Conrad C, Xia F, Park JS, Payer B, Yin Y, et al. (2009). Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell, 16: 425-438
[18] Stockton RA, Shenkar R, Awad IA, Ginsberg MH (2010). Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity. J Exp Med, 207: 881-896
[19] Zhou D, Medoff BD, Chen L, Li L, Zhang XF, Praskova M, et al. (2008). The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naive T cells. Proc Natl Acad Sci U S A, 105: 20321-20326
[20] Zhou D, Zhang Y, Wu H, Barry E, Yin Y, Lawrence E, et al. (2011). Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci U S A, 108: E1312-1320
[21] Gao T, Zhou D, Yang C, Singh T, Penzo-Mendez A, Maddipati R, et al. (2013). Hippo signaling regulates differentiation and maintenance in the exocrine pancreas. Gastroenterology, 144: 1543-1553, 1553 e1541
[22] Yuan Z, Lehtinen MK, Merlo P, Villen J, Gygi S, Bonni A (2009). Regulation of neuronal cell death by MST1-FOXO1 signaling. J Biol Chem, 284: 11285-11292
[23] Matsuki T, Zaka M, Guerreiro R, van der Brug MP, Cooper JA, Cookson MR, et al. (2012). Identification of Stk25 as a genetic modifier of Tau phosphorylation in Dab1-mutant mice. PLoS One, 7: e31152
[24] Zhou TH, Ling K, Guo J, Zhou H, Wu YL, Jing Q, et al. (2000). Identification of a human brain-specific isoform of mammalian STE20-like kinase 3 that is regulated by cAMP-dependent protein kinase. J Biol Chem, 275: 2513-2519
[25] Liu W, Wu J, Xiao L, Bai Y, Qu A, Zheng Z, et al. (2012). Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway. PLoS One, 7: e36562
[26] Thompson BJ, Sahai E (2015). MST kinases in development and disease. J Cell Biol, 210: 871-882
[27] Zalvide J, Fidalgo M, Fraile M, Guerrero A, Iglesias C, Floridia E, et al. (2013). The CCM3-GCKIII partnership. Histol Histopathol, 28: 1265-1272
[28] Chan EH, Nousiainen M, Chalamalasetty RB, Schafer A, Nigg EA, Sillje HH (2005). The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene, 24: 2076-2086
[29] Praskova M, Xia F, Avruch J (2008). MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr Biol, 18: 311-321
[30] Zhao B, Li L, Tumaneng K, Wang CY, Guan KL (2010). A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). Genes Dev, 24: 72-85
[31] Moroishi T, Park HW, Qin B, Chen Q, Meng Z, Plouffe SW, et al. (2015). A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. Genes Dev, 29: 1271-1284
[32] Hong W, Guan KL (2012). The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian Hippo pathway. Semin Cell Dev Biol, 23: 785-793
[33] Wu H, Xiao Y, Zhang S, Ji S, Wei L, Fan F, et al. (2013). The Ets transcription factor GABP is a component of the hippo pathway essential for growth and antioxidant defense. Cell Rep, 3: 1663-1677
[34] Fernandez BG, Gaspar P, Bras-Pereira C, Jezowska B, Rebelo SR, Janody F (2011). Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila. Development, 138: 2337-2346
[35] Lucas EP, Khanal I, Gaspar P, Fletcher GC, Polesello C, Tapon N, et al. (2013). The Hippo pathway polarizes the actin cytoskeleton during collective migration of Drosophila border cells. J Cell Biol, 201: 875-885
[36] Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, et al. (2006). A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell, 125: 987-1001
[37] Valis K, Prochazka L, Boura E, Chladova J, Obsil T, Rohlena J, et al. (2011). Hippo/Mst1 stimulates transcription of the proapoptotic mediator NOXA in a FoxO1-dependent manner. Cancer Res, 71: 946-954
[38] Chung C, Kim T, Kim M, Kim M, Song H, Kim TS, et al. (2013). Hippo-Foxa2 signaling pathway plays a role in peripheral lung maturation and surfactant homeostasis. Proc Natl Acad Sci U S A, 110: 7732-7737
[39] Choi J, Oh S, Lee D, Oh HJ, Park JY, Lee SB, et al. (2009). Mst1-FoxO signaling protects Naive T lymphocytes from cellular oxidative stress in mice. PLoS One, 4: e8011
[40] Ura S, Nishina H, Gotoh Y, Katada T (2007). Activation of the c-Jun N-terminal kinase pathway by MST1 is essential and sufficient for the induction of chromatin condensation during apoptosis. Mol Cell Biol, 27: 5514-5522
[41] Densham RM, O’Neill E, Munro J, Konig I, Anderson K, Kolch W, et al. (2009). MST kinases monitor actin cytoskeletal integrity and signal via c-Jun N-terminal kinase stress-activated kinase to regulate p21Waf1/Cip1 stability. Mol Cell Biol, 29: 6380-6390
[42] Lu TJ, Lai WY, Huang CY, Hsieh WJ, Yu JS, Hsieh YJ, et al. (2006). Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST. J Biol Chem, 281: 38405-38417
[43] ten Klooster JP, Jansen M, Yuan J, Oorschot V, Begthel H, Di Giacomo V, et al. (2009). Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex. Dev Cell, 16: 551-562
[44] Fuller SJ, McGuffin LJ, Marshall AK, Giraldo A, Pikkarainen S, Clerk A, et al. (2012). A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3). Biochem J, 442: 595-610
[45] Madsen CD, Hooper S, Tozluoglu M, Bruckbauer A, Fletcher G, Erler JT, et al. (2015). STRIPAK components determine mode of cancer cell migration and metastasis. Nat Cell Biol, 17: 68-80
[46] Halle M, Liu YC, Hardy S, Theberge JF, Blanchetot C, Bourdeau A, et al. (2007). Caspase-3 regulates catalytic activity and scaffolding functions of the protein tyrosine phosphatase PEST, a novel modulator of the apoptotic response. Mol Cell Biol, 27: 1172-1190
[47] Stegert MR, Hergovich A, Tamaskovic R, Bichsel SJ, Hemmings BA (2005). Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3. Mol Cell Biol, 25: 11019-11029
[48] Ultanir SK, Yadav S, Hertz NT, Oses-Prieto JA, Claxton S, Burlingame AL, et al. (2014). MST3 kinase phosphorylates TAO1/2 to enable Myosin Va function in promoting spine synapse development. Neuron, 84: 968-982
[49] Zhao B, Li L, Lu Q, Wang LH, Liu CY, Lei Q, et al. (2011). Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev, 25: 51-63
[50] Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, et al. (2011). Role of YAP/TAZ in mechanotransduction. Nature, 474: 179-183
[51] Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, et al. (2012). Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell, 150: 780-791
[52] Avruch J, Zhou D, Fitamant J, Bardeesy N, Mou F, Barrufet LR (2012). Protein kinases of the Hippo pathway: regulation and substrates. Semin Cell Dev Biol, 23: 770-784
[53] Scheel H, Hofmann K (2003). A novel interaction motif, SARAH, connects three classes of tumor suppressor. Curr Biol, 13: R899-900
[54] Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA, Haber D, et al. (2002). salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell, 110: 467-478
[55] Song H, Oh S, Oh HJ, Lim DS (2010). Role of the tumor suppressor RASSF2 in regulation of MST1 kinase activity. Biochem Biophys Res Commun, 391: 969-973
[56] Lee KK, Murakawa M, Nishida E, Tsubuki S, Kawashima S, Sakamaki K, et al. (1998). Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase during apoptosis. Oncogene, 16: 3029-3037
[57] Lee KK, Ohyama T, Yajima N, Tsubuki S, Yonehara S (2001). MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation. J Biol Chem, 276: 19276-19285
[58] Song JJ, Lee YJ (2008). Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily. Cell Signal, 20: 892-906
[59] Ribeiro PS, Josue F, Wepf A, Wehr MC, Rinner O, Kelly G, et al. (2010). Combined functional genomic and proteomic approaches identify a PP2A complex as a negative regulator of Hippo signaling. Mol Cell, 39: 521-534
[60] Poon CL, Lin JI, Zhang X, Harvey KF (2011). The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. Dev Cell, 21: 896-906
[61] Huang CY, Wu YM, Hsu CY, Lee WS, Lai MD, Lu TJ, et al. (2002). Caspase activation of mammalian sterile 20-like kinase 3 (Mst3). Nuclear translocation and induction of apoptosis. J Biol Chem, 277: 34367-34374
[62] Dong Y, Du X, Ye J, Han M, Xu T, Zhuang Y, et al. (2009). A cell-intrinsic role for Mst1 in regulating thymocyte egress. J Immunol, 183: 3865-3872
[63] Mou F, Praskova M, Xia F, Van Buren D, Hock H, Avruch J, et al. (2012). The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. J Exp Med, 209: 741-759
[64] Lu L, Li Y, Kim SM, Bossuyt W, Liu P, Qiu Q, et al. (2010). Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc Natl Acad Sci U S A, 107: 1437-1442
[65] Yamamoto S, Yang G, Zablocki D, Liu J, Hong C, Kim SJ, et al. (2003). Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy. J Clin Invest, 111: 1463-1474
[66] von Gise A, Lin Z, Schlegelmilch K, Honor LB, Pan GM, Buck JN, et al. (2012). YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc Natl Acad Sci U S A, 109: 2394-2399
[67] Xiao L, Chen D, Hu P, Wu J, Liu W, Zhao Y, et al. (2011). The c-Abl-MST1 signaling pathway mediates oxidative stress-induced neuronal cell death. J Neurosci, 31: 9611-9619
[68] Lee SJ, Seo BR, Choi EJ, Koh JY (2014). The role of reciprocal activation of cAbl and Mst1 in the oxidative death of cultured astrocytes. Glia, 62: 639-648
[69] Lee SJ, Cho KS, Kim HN, Kim HJ, Koh JY (2011). Role of zinc metallothionein-3 (ZnMt3) in epidermal growth factor (EGF)-induced c-Abl protein activation and actin polymerization in cultured astrocytes. J Biol Chem, 286: 40847-40856
[70] Yun HJ, Yoon JH, Lee JK, Noh KT, Yoon KW, Oh SP, et al. (2011). Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling. EMBO J, 30: 2465-2476
[71] Tang J, Ip JP, Ye T, Ng YP, Yung WH, Wu Z, et al. (2014). Cdk5-dependent Mst3 phosphorylation and activity regulate neuronal migration through RhoA inhibition. J Neurosci, 34: 7425-7436
[72] Irwin N, Li YM, O’Toole JE, Benowitz LI (2006). Mst3b, a purine-sensitive Ste20-like protein kinase, regulates axon outgrowth. Proc Natl Acad Sci U S A, 103: 18320-18325
[73] He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H, et al. (2010). Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development. Sci Signal, 3: ra26
[74] Fidalgo M, Guerrero A, Fraile M, Iglesias C, Pombo CM, Zalvide J (2012). Adaptor protein cerebral cavernous malformation 3 (CCM3) mediates phosphorylation of the cytoskeletal proteins ezrin/radixin/moesin by mammalian Ste20-4 to protect cells from oxidative stress. J Biol Chem, 287: 11556-11565
[75] Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, et al. (2007). PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway. Mol Biol Cell, 18: 1965-1978
[76] Zhang H, Ma X, Deng X, Chen Y, Mo X, Zhang Y, et al. (2012). PDCD10 interacts with STK25 to accelerate cell apoptosis under oxidative stress. Front Biosci (Landmark Ed), 17: 2295-2305
[77] Matsuki T, Matthews RT, Cooper JA, van der Brug MP, Cookson MR, Hardy JA, et al. (2010). Reelin and stk25 have opposing roles in neuronal polarization and dendritic Golgi deployment. Cell, 143: 826-836
[78] Rice DS, Curran T (2001). Role of the reelin signaling pathway in central nervous system development. Annu Rev Neurosci, 24: 1005-1039
[79] Matsuki T, Chen J, Howell BW (2013). Acute inactivation of the serine-threonine kinase Stk25 disrupts neuronal migration. Neural Dev, 8: 21
[80] Minoo P, Zlobec I, Baker K, Tornillo L, Terracciano L, Jass JR, et al. (2007). Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer. Mod Pathol, 20: 331-338
[81] Kim TS, Lee DH, Kim SK, Shin SY, Seo EJ, Lim DS (2012). Mammalian sterile 20-like kinase 1 suppresses lymphoma development by promoting faithful chromosome segregation. Cancer Res, 72: 5386-5395
[82] Fernandez LA, Northcott PA, Dalton J, Fraga C, Ellison D, Angers S, et al. (2009). YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes Dev, 23: 2729-2741
[83] Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T, et al. (2011). LATS2 is a tumor suppressor gene of malignant mesothelioma. Cancer Res, 71: 873-883
[84] Lau AN, Curtis SJ, Fillmore CM, Rowbotham SP, Mohseni M, Wagner DE, et al. (2014). Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis. EMBO J, 33: 468-481
[85] Li W, Cooper J, Zhou L, Yang C, Erdjument-Bromage H, Zagzag D, et al. (2014). Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-mediated inhibition of the hippo pathway kinases Lats1 and 2 in the nucleus. Cancer Cell, 26: 48-60
[86] Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW, Jaenisch R, et al. (2007). YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol, 17: 2054-2060
[87] Schulz A, Zoch A, Morrison H (2014). A neuronal function of the tumor suppressor protein merlin. Acta Neuropathol Commun, 2: 82
[88] Zhang H, Geng D, Gao J, Qi Y, Shi Y, Wang Y, et al. (2016). Expression and significance of Hippo/YAP signaling in glioma progression. Tumour Biol
[89] Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116: 281-297
[90] Ambros V (2004). The functions of animal microRNAs. Nature, 431: 350-355
[91] Zhu G, Wang Y, Mijiti M, Wang Z, Wu PF, Jiafu D (2015). Upregulation of miR-130b enhances stem cell-like phenotype in glioblastoma by inactivating the Hippo signaling pathway. Biochem Biophys Res Commun, 465: 194-199
[92] Cassinelli G, Zuco V, Gatti L, Lanzi C, Zaffaroni N, Colombo D, et al. (2013). Targeting the Akt kinase to modulate survival, invasiveness and drug resistance of cancer cells. Curr Med Chem, 20: 1923-1945
[93] Amornphimoltham P, Sriuranpong V, Patel V, Benavides F, Conti CJ, Sauk J, et al. (2004). Persistent activation of the Akt pathway in head and neck squamous cell carcinoma: a potential target for UCN-01. Clin Cancer Res, 10: 4029-4037
[94] Qi Z, Yan F, Shi W, Zhang C, Dong W, Zhao Y, et al. (2014). AKT-related autophagy contributes to the neuroprotective efficacy of hydroxysafflor yellow A against ischemic stroke in rats. Transl Stroke Res, 5: 501-509
[95] Akhavan D, Cloughesy TF, Mischel PS (2010). mTOR signaling in glioblastoma: lessons learned from bench to bedside. Neuro Oncol, 12: 882-889
[96] Sami A, Karsy M (2013). Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma: novel therapeutic agents and advances in understanding. Tumour Biol, 34: 1991-2002
[97] Chao Y, Wang Y, Liu X, Ma P, Shi Y, Gao J, et al. (2015). Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway. J Neurooncol, 121: 279-288
[98] Tozluoglu M, Mao Y, Bates PA, Sahai E (2015). Cost-benefit analysis of the mechanisms that enable migrating cells to sustain motility upon changes in matrix environments. J R Soc Interface, 12
[99] Costa B, Kean MJ, Ast V, Knight JD, Mett A, Levy Z, et al. (2012). STK25 protein mediates TrkA and CCM2 protein-dependent death in pediatric tumor cells of neural origin. J Biol Chem, 287: 29285-29289
[100] Harel L, Costa B, Tcherpakov M, Zapatka M, Oberthuer A, Hansford LM, et al. (2009). CCM2 mediates death signaling by the TrkA receptor tyrosine kinase. Neuron, 63: 585-591
[101] Fisher M, Vasilevko V, Cribbs DH (2012). Mixed cerebrovascular disease and the future of stroke prevention. Transl Stroke Res, 3: 39-51
[102] Zhu L, He D, Han L, Cao H (2015). Stroke Research in China over the Past Decade: Analysis of NSFC Funding. Transl Stroke Res, 6: 253-256
[103] Munyon CN, Hart DJ (2015). Vascular disease of the spine. Neurologist, 19: 121-127
[104] Zheng X, Xu C, Di Lorenzo A, Kleaveland B, Zou Z, Seiler C, et al. (2010). CCM3 signaling through sterile 20-like kinases plays an essential role during zebrafish cardiovascular development and cerebral cavernous malformations. J Clin Invest, 120: 2795-2804
[105] Revencu N, Vikkula M (2006). Cerebral cavernous malformation: new molecular and clinical insights. J Med Genet, 43: 716-721
[106] Voss K, Stahl S, Schleider E, Ullrich S, Nickel J, Mueller TD, et al. (2007). CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations. Neurogenetics, 8: 249-256
[107] Sveinsson OA, Kjartansson O, Valdimarsson EM (2014). [Cerebral ischemia/infarction - epidemiology, causes and symptoms]. Laeknabladid, 100: 271-279
[108] Zhao S, Yin J, Zhou L, Yan F, He Q, Huang L, et al. (2016). Hippo/MST1 signaling mediates microglial activation following acute cerebral ischemia-reperfusion injury. Brain Behav Immun, 55: 236-248
[109] Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, et al. (2005). ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci, 8: 752-758
[110] Korzhevskii DE, Lentsman MV, Kirik OV, Otellin VA (2012). [Morphological types of activated microglia in the hippocampus observed following transient total brain ischemia]. Morfologiia, 142: 30-33
[111] Kaushal V, Schlichter LC (2008). Mechanisms of microglia-mediated neurotoxicity in a new model of the stroke penumbra. J Neurosci, 28: 2221-2230
[112] Weng L, Wu Z, Zheng W, Meng H, Han L, Wang S, et al. (2016). Malibatol A enhances alternative activation of microglia by inhibiting phosphorylation of Mammalian Ste20-like kinase1 in OGD-BV-2 cells. Neurol Res, 38: 342-348
[113] Orihuela R, McPherson CA, Harry GJ (2016). Microglial M1/M2 polarization and metabolic states. Br J Pharmacol, 173: 649-665
[114] Li N, Liu BW, Ren WZ, Liu JX, Li SN, Fu SP, et al. (2016). GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-kappaB Signaling Pathways. Int J Mol Sci, 17: 190
[115] Yang Y, Wang L, Wu Y, Su D, Wang N, Wang J, et al. (2016). Tanshinol suppresses inflammatory factors in a rat model of vascular dementia and protects LPS-treated neurons via the MST1-FOXO3 signaling pathway. Brain Res, 1646: 304-314
[116] Nagata K (2014). [Alzheimer’s disease and vascular dementia]. Nihon Rinsho, 72: 618-630
[117] Kumawat KL, Kaushik DK, Goswami P, Basu A (2014). Acute exposure to lead acetate activates microglia and induces subsequent bystander neuronal death via caspase-3 activation. Neurotoxicology, 41: 143-153
[118] Bruning CA, Prigol M, Luchese C, Jesse CR, Duarte MM, Roman SS, et al. (2012). Protective effect of diphenyl diselenide on ischemia and reperfusion-induced cerebral injury: involvement of oxidative stress and pro-inflammatory cytokines. Neurochem Res, 37: 2249-2258
[119] Chodobski A, Zink BJ, Szmydynger-Chodobska J (2011). Blood-brain barrier pathophysiology in traumatic brain injury. Transl Stroke Res, 2: 492-516
[120] Zuliani G, Guerra G, Ranzini M, Rossi L, Munari MR, Zurlo A, et al. (2007). High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia. Int J Geriatr Psychiatry, 22: 305-311
[121] Gallacher J, Bayer A, Lowe G, Fish M, Pickering J, Pedro S, et al. (2010). Is sticky blood bad for the brain?: Hemostatic and inflammatory systems and dementia in the Caerphilly Prospective Study. Arterioscler Thromb Vasc Biol, 30: 599-604
[122] Gao LB, Yu XF, Chen Q, Zhou D (2016). Alzheimer’s Disease therapeutics: current and future therapies. Minerva Med, 107: 108-113
[123] Tulsulkar J, Glueck B, Hinds TDJr., Shah ZA (2016). Ginkgo biloba Extract Prevents Female Mice from Ischemic Brain Damage and the Mechanism Is Independent of the HO1/Wnt Pathway. Transl Stroke Res, 7: 120-131
[124] Trojanowski JQ, Lee VM (2002). The role of tau in Alzheimer’s disease. Med Clin North Am, 86: 615-627
[125] Hardy J, Orr H (2006). The genetics of neurodegenerative diseases. J Neurochem, 97: 1690-1699
[126] Peters OM, Ghasemi M, Brown RHJr., (2015). Emerging mechanisms of molecular pathology in ALS. J Clin Invest, 125: 1767-1779
[127] Rodrigues MC, Voltarelli JC, Sanberg PR, Borlongan CV, Garbuzova-Davis S (2012). Immunological aspects in amyotrophic lateral sclerosis. Transl Stroke Res, 3: 331-340
[128] Cleveland DW, Rothstein JD (2001). From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci, 2: 806-819
[129] Pasinelli P, Brown RH (2006). Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci, 7: 710-723
[130] Lee JK, Shin JH, Hwang SG, Gwag BJ, McKee AC, Lee J, et al. (2013). MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS. Proc Natl Acad Sci U S A, 110: 12066-12071
[131] Chae JS, Gil Hwang S, Lim DS, Choi EJ (2012). Thioredoxin-1 functions as a molecular switch regulating the oxidative stress-induced activation of MST1. Free Radic Biol Med, 53: 2335-2343
[132] Dewil M, dela Cruz VF, Van Den Bosch L, Robberecht W (2007). Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1(G93A)-induced motor neuron death. Neurobiol Dis, 26: 332-341
[133] Li M, Ona VO, Guegan C, Chen M, Jackson-Lewis V, Andrews LJ, et al. (2000). Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science, 288: 335-339
[134] Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, et al. (2006). Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature, 441: 885-889
[135] Prusiner SB (1991). Molecular biology of prion diseases. Science, 252: 1515-1522
[136] Brown DR, Schmidt B, Kretzschmar HA (1996). Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Nature, 380: 345-347
[137] Turnbull S, Tabner BJ, Brown DR, Allsop D (2003). Quinacrine acts as an antioxidant and reduces the toxicity of the prion peptide PrP106-126. Neuroreport, 14: 1743-1745
[138] Pan B, Yang L, Wang J, Wang Y, Wang J, Zhou X, et al. (2014). C-Abl tyrosine kinase mediates neurotoxic prion peptide-induced neuronal apoptosis via regulating mitochondrial homeostasis. Mol Neurobiol, 49: 1102-1116
[139] Burns AS, O’Connell C (2012). The challenge of spinal cord injury care in the developing world. J Spinal Cord Med, 35: 3-8
[140] An C, Jiang X, Pu H, Hong D, Zhang W, Hu X, et al. (2016). Severity-Dependent Long-Term Spatial Learning-Memory Impairment in a Mouse Model of Traumatic Brain Injury. Transl Stroke Res, 7: 512-520
[141] Terson de Paleville DG, McKay WB, Folz RJ, Ovechkin AV (2011). Respiratory motor control disrupted by spinal cord injury: mechanisms, evaluation, and restoration. Transl Stroke Res, 2: 463-473
[142] Zhang Y, Hu H, Tian T, Zhang L, Zhao D, Wu Q, et al. (2015). Mst3b promotes spinal cord neuronal regeneration by promoting growth cone branching out in spinal cord injury rats. Mol Neurobiol, 51: 1144-1157
[143] Doherty ES, Lacbawan FL (1993) 2q37 Microdeletion Syndrome. In GeneReviews(R) (PagonR. A., AdamM. P., ArdingerH. H., WallaceS. E., AmemiyaA., BeanL. J. H., et al., eds), Seattle (WA)
[144] Aldred MA, Sanford RO, Thomas NS, Barrow MA, Wilson LC, Brueton LA, et al. (2004). Molecular analysis of 20 patients with 2q37.3 monosomy: definition of minimum deletion intervals for key phenotypes. J Med Genet, 41: 433-439
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