SNRK: a metabolic regulator with multifaceted role in development and disease

Karthikeyan Thirugnanam , Ramani Ramchandran

Vessel Plus ›› 2020, Vol. 4 ›› Issue (1) : 26

PDF
Vessel Plus ›› 2020, Vol. 4 ›› Issue (1) :26 DOI: 10.20517/2574-1209.2020.18
Review
Review

SNRK: a metabolic regulator with multifaceted role in development and disease

Author information +
History +
PDF

Abstract

Sucrose nonfermenting 1-related kinase (SNRK) is a serine/threonine kinase and a member of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) family that is involved in the metabolic regulatory mechanisms in various cell types. SNRK is an important mediator in maintaining cellular metabolic homeostasis. In this review, we discuss the role of SNRK in metabolic tissues where it is expressed, including heart and adipose tissue. We discuss its role in regulating inflammation in these tissues and the pathways associated with regulating inflammation. We also discuss SNRK’s role in vascular development and the processes associated with it. Finally, we review SNRK’s potential as a target in various metabolic dysfunction-associated diseases such as cardiovascular diseases, diabetes, obesity, and cancer. This comprehensive review on SNRK suggests that it has therapeutic value in the suppression of inflammation in cardiac and adipose tissue.

Keywords

Sucrose nonfermenting 1-related kinase / metabolism / inflammation / cardiac function / cardiomyocytes / ischemia / adipocyte / endothelial cells

Cite this article

Download citation ▾
Karthikeyan Thirugnanam, Ramani Ramchandran. SNRK: a metabolic regulator with multifaceted role in development and disease. Vessel Plus, 2020, 4(1): 26 DOI:10.20517/2574-1209.2020.18

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Hunter T.A thousand and one protein kinases..Cell1987;50:823-9

[2]

Pereira SF,Dworkin J.Eukaryote-like serine/threonine kinases and phosphatases in bacteria..Microbiol Mol Biol Rev2011;75:192-212 PMCID:PMC3063355

[3]

Kyriakis JM.In the beginning, there was protein phosphorylation..J Biol Chem2014;289:9460-2 PMCID:PMC3974995

[4]

Hanks SK.Protein kinases 6. The eukaryotic protein kinase superfamily: kinase [catalytic] domain structure and classification..FASEB J1995;9:576-96

[5]

Thiel G,Rössler OG.Regulation of cellular proliferation, differentiation and cell death by activated Raf..Cell Commun Signal2009;7:8 PMCID:PMC2676293

[6]

Sharma PS,Tyagi T.Receptor tyrosine kinase inhibitors as potent weapons in war against cancers..Curr Pharm Des2009;15:758-76

[7]

Roskoski R Jr.Src kinase regulation by phosphorylation and dephosphorylation..Biochem Biophys Res Commun2005;331:1-14

[8]

Nolen B,Ghosh G.Regulation of protein kinases; controlling activity through activation segment conformation..Mol Cell2004;15:661-75

[9]

Becker W,Kentrup H.Molecular cloning and characterization of a novel mammalian protein kinase harboring a homology domain that defines a subfamily of serine/threonine kinases..Eur J Biochem1996;235:736-43

[10]

Wang YL,Chen X,Wu JW.Crystal structure of the kinase and UBA domains of SNRK reveals a distinct UBA binding mode in the AMPK family..Biochem Biophys Res Commun2018;495:1-6

[11]

Jaleel M,Lizcano JM,Toth R.Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate..FEBS Lett2005;579:1417-23

[12]

Rines AK,Fernandez RP,Ardehali H.Snf1-related kinase inhibits colon cancer cell proliferation through calcyclin-binding protein-dependent reduction of β-catenin..FASEB J2012;26:4685-95 PMCID:PMC3475258

[13]

Cossette SM,Bao X,Horswill MA.Sucrose nonfermenting-related kinase enzyme-mediated rho-associated kinase signaling is responsible for cardiac function..Circ Cardiovasc Genet2016;9:474-86 PMCID:PMC5177517

[14]

Thirugnanam K,Lu Q,Harmann LM.Cardiomyocyte-specific snrk prevents inflammation in the heart..J Am Heart Assoc2019;8:e012792 PMCID:PMC6915262

[15]

Cossette SM,Bao X,Zhong L.Sucrose non-fermenting related kinase enzyme is essential for cardiac metabolism..Biol Open2014;4:48-61 PMCID:PMC4295165

[16]

Rines AK,Wu R,Khechaduri A.Snf1-related kinase improves cardiac mitochondrial efficiency and decreases mitochondrial uncoupling..Nat Commun2017;8:14095 PMCID:PMC5286102

[17]

Li J,Lai S,Liu S.Dysregulation of PP2A-Akt interaction contributes to Sucrose non-fermenting related kinase (SNRK) deficiency induced insulin resistance in adipose tissue..Mol Metab2019;28:26-35 PMCID:PMC6822176

[18]

Li J,Nie Y,Lin X.Sucrose nonfermenting-related kinase regulates both adipose inflammation and energy homeostasis in mice and humans..Diabetes2018;67:400-11 PMCID:PMC5828454

[19]

Li Y,Helou Y,Feng B.Identification of sucrose non-fermenting-related kinase (SNRK) as a suppressor of adipocyte inflammation..Diabetes2013;62:2396-409 PMCID:PMC3712026

[20]

Pramanik K,Garnaas MK,Li K.Dusp-5 and Snrk-1 coordinately function during vascular development and disease..Blood2009;113:1184-91 PMCID:PMC2635084

[21]

Lu Q,Yan C,Ma Z.SNRK (sucrose nonfermenting 1-related kinase) promotes angiogenesis in vivo..Arterioscler Thromb Vasc Biol2018;38:373-85 PMCID:PMC5785416

[22]

Lu Q,Ding Y,Chen L.Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis..Nat Commun2019;10:2145 PMCID:PMC6513984

[23]

Hopp EE,Kumar SN,Ramchandran R.Sucrose non-fermenting related kinase expression in ovarian cancer and correlation with clinical features..Cancer Invest2017;35:456-62 PMCID:PMC6167932

[24]

Yoshida K,Nishio C,Hatanaka H.SNRK, a member of the SNF1 family, is related to low K[+]-induced apoptosis of cultured rat cerebellar granule neurons..Brain Res2000;873:274-82

[25]

Manning G,Martinez R,Sudarsanam S.The protein kinase complement of the human genome..Science2002;298:1912-34

[26]

Bright NJ,Carling D.The regulation and function of mammalian AMPK-related kinases..Acta Physiol (Oxf)2009;196:15-26

[27]

Rider MH.The ubiquitin-associated domain of AMPK-related protein kinases allows LKB1-induced phosphorylation and activation..Biochem J2006;394:e7-9 PMCID:PMC1383723

[28]

Chen L,Zheng LS,Xie ST.Structural insight into the autoinhibition mechanism of AMP-activated protein kinase..Nature2009;459:1146-9

[29]

Shaw RJ,Bardeesy N,Witters LA.The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress..Proc Natl Acad Sci U S A2004;101:3329-35 PMCID:PMC373461

[30]

Alessi DR,Bayascas JR.LKB1-dependent signaling pathways..Annu Rev Biochem2006;75:137-63

[31]

Sapkota GP,Deak M,Morrice N.Identification and characterization of four novel phosphorylation sites (Ser31, Ser325, Thr336 and Thr366) on LKB1/STK11, the protein kinase mutated in Peutz-Jeghers cancer syndrome..Biochem J2002;362:481-90 PMCID:PMC1222410

[32]

Sapkota GP,Lizcano JM,Arthur JS.Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth..J Biol Chem2001;276:19469-82

[33]

Hemminki A,Tomlinson I,Roth S.A serine/threonine kinase gene defective in Peutz-Jeghers syndrome..Nature1998;391:184-7

[34]

Baas AF,Sapkota GP,Medema R.Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD..EMBO J2003;22:3062-72 PMCID:PMC162144

[35]

Boudeau J,Deak M,Kieloch A.MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm..EMBO J2003;22:5102-14 PMCID:PMC204473

[36]

Xie Z,Zhang J,Neumann D.Identification of the serine 307 of LKB1 as a novel phosphorylation site essential for its nucleocytoplasmic transport and endothelial cell angiogenesis..Mol Cell Biol2009;29:3582-96 PMCID:PMC2698771

[37]

Boudeau J,Resta N,Kieloch A.Analysis of the LKB1-STRAD-MO25 complex..J Cell Sci2004;117:6365-75

[38]

Nakano H,Braas D,Wu X.Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis..Elife2017;6:e29330 PMCID:PMC5726851

[39]

Bartelds B,Smid GB,Visser GH.Perinatal changes in myocardial metabolism in lambs..Circulation2000;102:926-31

[40]

Fisher DJ,Rudolph AM.Myocardial oxygen and carbohydrate consumption in fetal lambs in utero and in adult sheep..Am J Physiol1980;238:H399-405

[41]

Warshaw JB.Cellular energy metabolism during fetal development. II. Fatty acid oxidation by the developing heart..J Cell Biol1970;44:354-60 PMCID:PMC2107947

[42]

Werner JC,Schuler HG.Palmitate oxidation by isolated working fetal and newborn pig hearts..Am J Physiol1989;256:E315-21

[43]

Piquereau J.Maturation of Cardiac Energy Metabolism During Perinatal Development..Front Physiol2018;9:959 PMCID:PMC6060230

[44]

Kolwicz SC Jr,Tian R.Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes..Circ Res2013;113:603-16 PMCID:PMC3845521

[45]

Wisneski JA,Neese RA,Craig JC.Dual carbon-labeled isotope experiments using D-(6-14C) glucose and L-(1,2,3-13C3) lactate: a new approach for investigating human myocardial metabolism during ischemia..J Am Coll Cardiol1985;5:1138-46

[46]

Gertz EW,Stanley WC.Myocardial substrate utilization during exercise in humans. Dual carbon-labeled carbohydrate isotope experiments..J Clin Invest1988;82:2017-25 PMCID:PMC442784

[47]

D’Souza K,Kienesberger PC.Lipid metabolism and signaling in cardiac lipotoxicity..Biochim Biophys Acta2016;1861:1513-24

[48]

Loirand G,Pacaud P.Rho kinases in cardiovascular physiology and pathophysiology..Circ Res2006;98:322-34

[49]

Du K,Kulkarni RN.TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver..Science.2003;300:1574-7

[50]

Rotter V,Smith U.Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects..J Biol Chem2003;278:45777-84

[51]

Skurk T,Herder C.Relationship between adipocyte size and adipokine expression and secretion..J Clin Endocrinol Metab2007;92:1023-33

[52]

Bernstein RS,Kipnis DM.Hyperinsulinemia and enlarged adipocytes in patients with endogenous hyperlipoproteinemia without obesity or diabetes mellitus..Diabetes1975;24:207-13

[53]

Brook CG.Adipose cell size and glucose tolerance in obese children and effects of diet..Arch Dis Child1973;48:301-4 PMCID:PMC1648325

[54]

McLaughlin T,Tsao P,Yee G.Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis..Diabetologia2007;50:1707-15

[55]

Weyer C,Bogardus C,Pratley RE.Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance..Diabetologia2000;Dec43:1498-506

[56]

Laforest S,Michaud A,Tchernof A.Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction..Crit Rev Clin Lab Sci2015;52:301-13

[57]

Ha EE.Emerging roles for adipose tissue in cardiovascular disease..Arterioscler Thromb Vasc Biol2018;38:e137-44 PMCID:PMC6205733

[58]

Veilleux A,Bellmann K.Chronic inhibition of the mTORC1/S6K1 pathway increases insulin-induced PI3K activity but inhibits Akt2 and glucose transport stimulation in 3T3-L1 adipocytes..Mol Endocrinol2010;24:766-78 PMCID:PMC5417537

[59]

Suthahar N,Silljé HHW.From inflammation to fibrosis-molecular and cellular mechanisms of myocardial tissue remodelling and perspectives on differential treatment opportunities..Curr Heart Fail Rep2017;14:235-50 PMCID:PMC5527069

[60]

Van Linthout S.Inflammation - cause or consequence of heart failure or both?.Curr Heart Fail Rep2017;14:251-65 PMCID:PMC5527060

[61]

Khan T,Iyengar P,Chandalia M.Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI..Mol Cell Biol2009;29:1575-91 PMCID:PMC2648231

[62]

Ko HJ,Jung DY,Ma Z.Nutrient stress activates inflammation and reduces glucose metabolism by suppressing AMP-activated protein kinase in the heart..Diabetes2009;58:2536-46 PMCID:PMC2768176

[63]

Tikellis C,Harcourt BE,Pete J.Cardiac inflammation associated with a Western diet is mediated via activation of RAGE by AGEs..Am J Physiol Endocrinol Metab2008;295:E323-30 PMCID:PMC2652498

[64]

Song X,Xiao CY,Rosenberg MA.mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy..Am J Physiol Cell Physiol2010;299:C1256-66 PMCID:PMC3006320

[65]

Palomer X,Barroso E.An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy..Int J Cardiol2013;168:3160-72

[66]

Travers JG,Robbins J,Blaxall BC.Cardiac fibrosis: the fibroblast awakens..Circ Res2016;118:1021-40 PMCID:PMC4800485

[67]

Blüher M.The distinction of metabolically ‘healthy’ from ‘unhealthy’ obese individuals..Curr Opin Lipidol2010;21:38-43

[68]

Wernstedt Asterholm I,Morley TS,Delgado-Lopez F.Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling..Cell Metab2014;20:103-18 PMCID:PMC4079756

[69]

Berg AH.Adipose tissue, inflammation, and cardiovascular disease..Circ Res2005;96:939-49

[70]

Carmeliet P,Breier G,Kieckens L.Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele..Nature1996;380:435-9

[71]

Risau W.Vasculogenesis..Annu Rev Cell Dev Biol1995;11:73-91

[72]

Prabhudesai S,Dey A,Leigh NR.Cystathionine β-synthase is necessary for axis development in vivo..Front Cell Dev Biol2018;6:14 PMCID:PMC5820354

[73]

Eisa-Beygi S,El-Rass S,Abdelrasoul MKA.Characterization of endothelial cilia distribution during cerebral-vascular development in Zebrafish [ Danio rerio]..Arterioscler Thromb Vasc Biol2018;38:2806-18 PMCID:PMC6309420

[74]

Leigh NR,Li K,Gastonguay A.Mmp17b is essential for proper neural crest cell migration in vivo..PLoS One2013;8:e76484 PMCID:PMC3788140

[75]

Pardanaud L,Dieterlen-Lievre F.Relationship between vasculogenesis, angiogenesis and haemopoiesis during avian ontogeny..Development1989;105:473-85

[76]

Chun CZ,Samant GV,Pramanik K.Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates..Blood2009;113:1192-9 PMCID:PMC2635085

[77]

Eriksson J.Development of the hypochord and dorsal aorta in the zebrafish embryo [Danio rerio]..J Morphol2000;244:167-76

[78]

Fouquet B,Serluca FC.Vessel patterning in the embryo of the zebrafish: guidance by notochord..Dev Biol1997;183:37-48

[79]

Sumanas S,Lin S.Identification of novel vascular endothelial-specific genes by the microarray analysis of the zebrafish cloche mutants..Blood2005;106:534-41 PMCID:PMC1895181

[80]

Eilken HM.Dynamics of endothelial cell behavior in sprouting angiogenesis..Curr Opin Cell Biol2010;22:617-25

[81]

Uemura A,Katsuta H.Angiogenesis in the mouse retina: a model system for experimental manipulation..Exp Cell Res2006;312:676-83

[82]

Nessa A,Siddiqui NI,Bhuiyan MR.Angiogenesis-a novel therapeutic approach for ischemic heart disease..Mymensingh Med J2009;18:264-72

[83]

Mori J,Oudit GY.Impact of the renin-angiotensin system on cardiac energy metabolism in heart failure..J Mol Cell Cardiol2013;63:98-106

[84]

Gottlieb RA.METABOLISM. Mitochondria shape cardiac metabolism..Science2015;350:1162-3

[85]

Pinto AR,Ivey MJ,D’Antoni ML.Revisiting cardiac cellular composition..Circ Res2016;118:400-9 PMCID:PMC4744092

[86]

Hafner AV,Gomes AP,Palmeira CM.Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy..Aging (Albany NY)2010;2:914-23 PMCID:PMC3034180

[87]

Pillai VB,Sundaresan NR,Kim G.Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3..Nat Commun2015;6:6656 PMCID:PMC4441304

[88]

Pillai VB,Fang YH,Samant S.Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice..Oncotarget2017;8:34082-98 PMCID:PMC5470953

[89]

Chen L,Wang H.Mechanisms Linking Inflammation to Insulin Resistance..Int J Endocrinol2015;2015:508409 PMCID:PMC4468292

[90]

Hanahan D.Hallmarks of cancer: the next generation..Cell2011;144:646-74

[91]

Avizienyte E,Roth S,Tarkkanen M.LKB1 somatic mutations in sporadic tumors..Am J Pathol1999;154:677-81 PMCID:PMC1868601

[92]

Bignell GR,Seal S,Warren W.Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer..Cancer Res1998;58:1384-6

[93]

Su GH,Bansal RK,Tang DJ.Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers..Am J Pathol1999;154:1835-40 PMCID:PMC1866632

[94]

Rowan A,MacKie R,Bicknell D.Somatic mutations in the Peutz-Jeghers [LKB1/STKII] gene in sporadic malignant melanomas..J Invest Dermatol1999;112:509-11

[95]

Qiu W,Thaker HM,Su GH.A novel mutation of STK11/LKB1 gene leads to the loss of cell growth inhibition in head and neck squamous cell carcinoma..Oncogene2006;25:2937-42 PMCID:PMC1459486

[96]

Kim CJ,Park JY,Lee JH.Genetic analysis of the LKB1/STK11 gene in hepatocellular carcinomas..Eur J Cancer2004;40:136-41

[97]

Powis G.Hypoxia inducible factor-1alpha as a cancer drug target..Mol Cancer Ther2004;3:647-54

[98]

Nie F,Wang XG,Wang LL.Down-regulation of CacyBP is associated with poor prognosis and the effects on COX-2 expression in breast cancer..Int J Oncol2010;37:1261-9

[99]

Ning X,Hong L,Liu L.Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer..Mol Cancer Res2007;5:1254-62

[100]

Sun S,Liu J,Chen Y.Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma..Biochem Biophys Res Commun2007;356:864-71

[101]

Nieman KM,Penicka CV,Buell-Gutbrod R.Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth..Nat Med2011;17:1498-503 PMCID:PMC4157349

PDF

49

Accesses

0

Citation

Detail

Sections
Recommended

/