메뉴 건너뛰기




Volumn 28, Issue 7, 2014, Pages 1186-1193

Convergence of IPMK and LKB1-AMPK signaling pathways on metformin action

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INOSITOL POLYPHOSPHATE; INOSITOL POLYPHOSPHATE MULTIKINASE; METFORMIN; PROTEIN KINASE LKB1; UNCLASSIFIED DRUG; 5 AMINO 4 IMIDAZOLECARBOXAMIDE; AICA RIBONUCLEOTIDE; ANTIDIABETIC AGENT; FATTY ACID; GLUCOSE; PHOSPHOTRANSFERASE; PROTEIN SERINE THREONINE KINASE; RIBONUCLEOTIDE; STK11 PROTEIN, MOUSE;

EID: 84903618241     PISSN: 08888809     EISSN: 19449917     Source Type: Journal    
DOI: 10.1210/me.2014-1134     Document Type: Article
Times cited : (38)

References (50)
  • 1
    • 0347318052 scopus 로고    scopus 로고
    • The AMP-activated protein kinase cascade-a unifying system for energy control
    • Carling D. The AMP-activated protein kinase cascade-a unifying system for energy control. Trends Biochem Sci. 2004;29:18-24.
    • (2004) Trends Biochem Sci. , vol.29 , pp. 18-24
    • Carling, D.1
  • 2
    • 0031007065 scopus 로고    scopus 로고
    • The AMP-activated protein kinase-fuel gauge of the mammalian cell?
    • Hardie DG, Carling D. The AMP-activated protein kinase-fuel gauge of the mammalian cell? Eur J Biochem. 1997;246:259-273.
    • (1997) Eur J Biochem. , vol.246 , pp. 259-273
    • Hardie, D.G.1    Carling, D.2
  • 3
    • 33745225026 scopus 로고    scopus 로고
    • AMP-activated protein kinase-development of the energy sensor concept
    • Hardie DG, Hawley SA, Scott JW. AMP-activated protein kinase-development of the energy sensor concept. J Physiol. 2006;574:7-15.
    • (2006) J Physiol. , vol.574 , pp. 7-15
    • Hardie, D.G.1    Hawley, S.A.2    Scott, J.W.3
  • 5
    • 34648828532 scopus 로고    scopus 로고
    • AMP-activated/SNF1 protein kinases: Conserved guardians of cellular energy
    • Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol. 2007;8:774-785.
    • (2007) Nat Rev Mol Cell Biol. , vol.8 , pp. 774-785
    • Hardie, D.G.1
  • 6
    • 23044432463 scopus 로고    scopus 로고
    • Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase
    • Hawley SA, Pan DA, Mustard KJ, et al. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2005;2:9-19.
    • (2005) Cell Metab. , vol.2 , pp. 9-19
    • Hawley, S.A.1    Pan, D.A.2    Mustard, K.J.3
  • 7
    • 23044437445 scopus 로고    scopus 로고
    • Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells
    • Woods A, Dickerson K, Heath R, et al. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2005;2:21-33.
    • (2005) Cell Metab. , vol.2 , pp. 21-33
    • Woods, A.1    Dickerson, K.2    Heath, R.3
  • 8
    • 0034773404 scopus 로고    scopus 로고
    • Role of AMP-activated protein kinase in mechanism of metformin action
    • Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108:1167-1174.
    • (2001) J Clin Invest. , vol.108 , pp. 1167-1174
    • Zhou, G.1    Myers, R.2    Li, Y.3
  • 9
    • 0032495530 scopus 로고    scopus 로고
    • A serine/threonine kinase gene defective in Peutz-Jeghers syndrome
    • Hemminki A, Markie D, Tomlinson I, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 1998; 391:184-187.
    • (1998) Nature. , vol.391 , pp. 184-187
    • Hemminki, A.1    Markie, D.2    Tomlinson, I.3
  • 10
    • 0031974516 scopus 로고    scopus 로고
    • Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase
    • Jenne DE, Reimann H, Nezu J, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18:38-43.
    • (1998) Nat Genet. , vol.18 , pp. 38-43
    • Jenne, D.E.1    Reimann, H.2    Nezu, J.3
  • 11
    • 0038614742 scopus 로고    scopus 로고
    • Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD
    • Baas AF, Boudeau J, Sapkota GP, et al. Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. EMBO J. 2003;22:3062-3072.
    • (2003) EMBO J. , vol.22 , pp. 3062-3072
    • Baas, A.F.1    Boudeau, J.2    Sapkota, G.P.3
  • 12
    • 0141753981 scopus 로고    scopus 로고
    • MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm
    • Boudeau J, Baas AF, Deak M, et al. MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. EMBO J. 2003;22:5102-5114.
    • (2003) EMBO J. , vol.22 , pp. 5102-5114
    • Boudeau, J.1    Baas, A.F.2    Deak, M.3
  • 13
    • 44949122687 scopus 로고    scopus 로고
    • STRADalpha regulates LKB1 localization by blocking access to importin-alpha, and by association with Crm1 and exportin-7
    • Dorfman J, Macara IG. STRADalpha regulates LKB1 localization by blocking access to importin-alpha, and by association with Crm1 and exportin-7. Mol Biol Cell. 2008;19:1614-1626.
    • (2008) Mol Biol Cell. , vol.19 , pp. 1614-1626
    • Dorfman, J.1    McAra, I.G.2
  • 14
    • 12144287284 scopus 로고    scopus 로고
    • LKB1 is a master kinase that activates 13 kinases of theAMPKsubfamily, including MARK/ PAR-1
    • Lizcano JM, Göransson O, Toth R, et al. LKB1 is a master kinase that activates 13 kinases of theAMPKsubfamily, including MARK/ PAR-1. EMBO J. 2004;23:833-843.
    • (2004) EMBO J. , vol.23 , pp. 833-843
    • Lizcano, J.M.1    Göransson, O.2    Toth, R.3
  • 15
    • 10744230065 scopus 로고    scopus 로고
    • LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
    • Woods A, Johnstone SR, Dickerson K, et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol. 2003;13:2004-2008.
    • (2003) Curr Biol. , vol.13 , pp. 2004-2008
    • Woods, A.1    Johnstone, S.R.2    Dickerson, K.3
  • 16
    • 56749176442 scopus 로고    scopus 로고
    • LKB1; linking cell structure and tumor suppression
    • Hezel AF, Bardeesy N. LKB1; linking cell structure and tumor suppression. Oncogene. 2008;27:6908-6919.
    • (2008) Oncogene. , vol.27 , pp. 6908-6919
    • Hezel, A.F.1    Bardeesy, N.2
  • 17
    • 67749111502 scopus 로고    scopus 로고
    • The LKB1-AMPK pathway: Metabolism and growth control in tumour suppression
    • Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 2009; 9:563-575.
    • (2009) Nat Rev Cancer. , vol.9 , pp. 563-575
    • Shackelford, D.B.1    Shaw, R.J.2
  • 18
    • 0345107247 scopus 로고    scopus 로고
    • Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    • Hawley SA, Boudeau J, Reid JL, et al. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol. 2003;2:28.
    • (2003) J Biol. , vol.2 , pp. 28
    • Hawley, S.A.1    Boudeau, J.2    Reid, J.L.3
  • 19
    • 1542618348 scopus 로고    scopus 로고
    • The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
    • Shaw RJ, Kosmatka M, Bardeesy N, et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A. 2004;101:3329-3335.
    • (2004) Proc Natl Acad Sci U S A. , vol.101 , pp. 3329-3335
    • Shaw, R.J.1    Kosmatka, M.2    Bardeesy, N.3
  • 20
    • 0033673203 scopus 로고    scopus 로고
    • Mechanism by which metformin reduces glucose production in type 2 diabetes
    • Hundal RS, Krssak M, Dufour S, et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes. 2000;49:2063-2069.
    • (2000) Diabetes. , vol.49 , pp. 2063-2069
    • Hundal, R.S.1    Krssak, M.2    Dufour, S.3
  • 22
    • 0034659785 scopus 로고    scopus 로고
    • Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain
    • Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000;348(Pt 3):607-614.
    • (2000) Biochem J. , vol.348 , Issue.PART 3 , pp. 607-614
    • Owen, M.R.1    Doran, E.2    Halestrap, A.P.3
  • 23
    • 28844433635 scopus 로고    scopus 로고
    • The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin
    • Shaw RJ, Lamia KA, Vasquez D, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005;310:1642-1646.
    • (2005) Science. , vol.310 , pp. 1642-1646
    • Shaw, R.J.1    Lamia, K.A.2    Vasquez, D.3
  • 24
    • 38049067500 scopus 로고    scopus 로고
    • Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK alpha2-subunit (PRKAA2) and risk of type 2 diabetes
    • Keshavarz P, Inoue H, Nakamura N, Yoshikawa T, Tanahashi T, Itakura M. Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK alpha2-subunit (PRKAA2) and risk of type 2 diabetes. Mol Genet Metab. 2008;93: 200-209.
    • (2008) Mol Genet Metab. , vol.93 , pp. 200-209
    • Keshavarz, P.1    Inoue, H.2    Nakamura, N.3    Yoshikawa, T.4    Tanahashi, T.5    Itakura, M.6
  • 25
    • 40849126625 scopus 로고    scopus 로고
    • Ovulatory response to treatment of polycystic ovary syndrome is associated with a polymorphism in the STK11 gene
    • Legro RS, Barnhart HX, Schlaff WD, et al. Ovulatory response to treatment of polycystic ovary syndrome is associated with a polymorphism in the STK11 gene. J Clin Endocrinol Metab. 2008;93: 792-800.
    • (2008) J Clin Endocrinol Metab. , vol.93 , pp. 792-800
    • Legro, R.S.1    Barnhart, H.X.2    Schlaff, W.D.3
  • 26
    • 77954933558 scopus 로고    scopus 로고
    • Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state
    • Foretz M, Hébrard S, Leclerc J, et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest. 2010;120: 2355-2369.
    • (2010) J Clin Invest. , vol.120 , pp. 2355-2369
    • Foretz, M.1    Hébrard, S.2    Leclerc, J.3
  • 27
    • 77955287742 scopus 로고    scopus 로고
    • Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner
    • Kalender A, Selvaraj A, Kim SY, et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 2010;11:390-401.
    • (2010) Cell Metab. , vol.11 , pp. 390-401
    • Kalender, A.1    Selvaraj, A.2    Kim, S.Y.3
  • 28
    • 84873707522 scopus 로고    scopus 로고
    • Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP
    • Miller RA, Chu Q, Xie J, Foretz M, Viollet B, Birnbaum MJ. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature. 2013;494:256-260.
    • (2013) Nature. , vol.494 , pp. 256-260
    • Miller, R.A.1    Chu, Q.2    Xie, J.3    Foretz, M.4    Viollet, B.5    Birnbaum, M.J.6
  • 29
    • 79952117625 scopus 로고    scopus 로고
    • SnapShot: Inositol phosphates
    • Hatch AJ, York JD. SnapShot: inositol phosphates. Cell. 2010;143: 1030.
    • (2010) Cell. , vol.143 , pp. 1030
    • Hatch, A.J.1    York, J.D.2
  • 30
    • 0035347166 scopus 로고    scopus 로고
    • Back in the water: The return of the inositol phosphates
    • Irvine RF, Schell MJ. Back in the water: the return of the inositol phosphates. Nat Rev Mol Cell Biol. 2001;2:327-338.
    • (2001) Nat Rev Mol Cell Biol. , vol.2 , pp. 327-338
    • Irvine, R.F.1    Schell, M.J.2
  • 31
    • 0035956860 scopus 로고    scopus 로고
    • Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5-trisphosphate and an inositol pyrophosphate
    • Saiardi A, Nagata E, Luo HR, et al. Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5-trisphosphate and an inositol pyrophosphate. Proc Natl Acad Sci U S A. 2001;98:2306-2311.
    • (2001) Proc Natl Acad Sci U S A. , vol.98 , pp. 2306-2311
    • Saiardi, A.1    Nagata, E.2    Luo, H.R.3
  • 32
    • 0942290439 scopus 로고    scopus 로고
    • How versatile are inositol phosphate kinases?
    • Shears SB. How versatile are inositol phosphate kinases? Biochem J. 2004;377:265-280.
    • (2004) Biochem J. , vol.377 , pp. 265-280
    • Shears, S.B.1
  • 33
    • 0020643801 scopus 로고
    • Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate
    • Streb H, Irvine RF, Berridge MJ, Schulz I. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature. 1983;306:67-69.
    • (1983) Nature. , vol.306 , pp. 67-69
    • Streb, H.1    Irvine, R.F.2    Berridge, M.J.3    Schulz, I.4
  • 34
    • 23844551508 scopus 로고    scopus 로고
    • Increased levels of inositol hexakisphosphate (InsP6) protect HEK293 cells from tumor necrosis factor (alpha)-and Fas-induced apoptosis
    • Verbsky J, Majerus PW. Increased levels of inositol hexakisphosphate (InsP6) protect HEK293 cells from tumor necrosis factor (alpha)-and Fas-induced apoptosis. J Biol Chem. 2005;280: 29263-29268.
    • (2005) J Biol Chem. , vol.280 , pp. 29263-29268
    • Verbsky, J.1    Majerus, P.W.2
  • 35
    • 84885086001 scopus 로고    scopus 로고
    • Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction
    • Xu R, Paul BD, Smith DR, et al. Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction. Proc Natl Acad Sci U S A. 2013;110:16181-16186.
    • (2013) Proc Natl Acad Sci U S A. , vol.110 , pp. 16181-16186
    • Xu, R.1    Paul, B.D.2    Smith, D.R.3
  • 36
    • 84876130866 scopus 로고    scopus 로고
    • Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death
    • Xu R, Sen N, Paul BD, et al. Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death. Sci Signal. 2013;6:ra22.
    • (2013) Sci Signal. , vol.6
    • Xu, R.1    Sen, N.2    Paul, B.D.3
  • 37
    • 0037205048 scopus 로고    scopus 로고
    • The phosphoinositide 3-kinase pathway
    • Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296:1655-1657.
    • (2002) Science. , vol.296 , pp. 1655-1657
    • Cantley, L.C.1
  • 38
    • 79551565620 scopus 로고    scopus 로고
    • Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase
    • Kim S, Kim SF, Maag D, et al. Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase. Cell Metab. 2011; 13:215-221.
    • (2011) Cell Metab. , vol.13 , pp. 215-221
    • Kim, S.1    Kim, S.F.2    Maag, D.3
  • 39
    • 79951885087 scopus 로고    scopus 로고
    • Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB
    • Maag D, Maxwell MJ, Hardesty DA, et al. Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB. Proc Natl Acad Sci U S A. 2011;108:1391-1396.
    • (2011) Proc Natl Acad Sci U S A. , vol.108 , pp. 1391-1396
    • Maag, D.1    Maxwell, M.J.2    Hardesty, D.A.3
  • 40
    • 84862884630 scopus 로고    scopus 로고
    • Direct modification and activation of a nuclear receptor-PIP(2) complex by the inositol lipid kinase IPMK
    • Blind RD, Suzawa M, Ingraham HA. Direct modification and activation of a nuclear receptor-PIP(2) complex by the inositol lipid kinase IPMK. Sci Signal 2012;5:ra44.
    • (2012) Sci Signal , vol.5
    • Blind, R.D.1    Suzawa, M.2    Ingraham, H.A.3
  • 41
    • 84862908394 scopus 로고    scopus 로고
    • AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase
    • Bang S, Kim S, Dailey MJ, et al. AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase. Proc Natl Acad Sci U S A. 2012;109:616-620.
    • (2012) Proc Natl Acad Sci U S A. , vol.109 , pp. 616-620
    • Bang, S.1    Kim, S.2    Dailey, M.J.3
  • 42
    • 79957904163 scopus 로고    scopus 로고
    • Nutrient amino acids signal to mTOR via inositol polyphosphate multikinase
    • Kim S, Snyder SH. Nutrient amino acids signal to mTOR via inositol polyphosphate multikinase. Cell Cycle. 2011;10:1708-1710.
    • (2011) Cell Cycle. , vol.10 , pp. 1708-1710
    • Kim, S.1    Snyder, S.H.2
  • 43
    • 84863096119 scopus 로고    scopus 로고
    • Striatum specific protein, Rhes regulates AKT pathway
    • Bang S, Steenstra C, Kim SF. Striatum specific protein, Rhes regulates AKT pathway. Neurosci Lett. 2012;521:142-147.
    • (2012) Neurosci Lett. , vol.521 , pp. 142-147
    • Bang, S.1    Steenstra, C.2    Kim, S.F.3
  • 46
    • 3843133857 scopus 로고    scopus 로고
    • The IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus
    • Kamimura J, Wakui K, Kadowaki H, et al. The IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus. J Hum Genet. 2004;49:360-365.
    • (2004) J Hum Genet. , vol.49 , pp. 360-365
    • Kamimura, J.1    Wakui, K.2    Kadowaki, H.3
  • 47
    • 45549094869 scopus 로고    scopus 로고
    • Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells
    • Song P, Xie Z, Wu Y, Xu J, Dong Y, Zou MH. Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells. J Biol Chem. 2008;283:12446-12455.
    • (2008) J Biol Chem. , vol.283 , pp. 12446-12455
    • Song, P.1    Xie, Z.2    Wu, Y.3    Xu, J.4    Dong, Y.5    Zou, M.H.6
  • 48
    • 84859863112 scopus 로고    scopus 로고
    • Nucleocytoplasmic shuttling of human inositol phosphate multikinase is influenced by CK2 phosphorylation
    • Meyer R, Nalaskowski MM, Ehm P, et al. Nucleocytoplasmic shuttling of human inositol phosphate multikinase is influenced by CK2 phosphorylation. Biol Chem. 2012;393:149-160.
    • (2012) Biol Chem. , vol.393 , pp. 149-160
    • Meyer, R.1    Nalaskowski, M.M.2    Ehm, P.3
  • 49
    • 39449096289 scopus 로고    scopus 로고
    • Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells
    • Xie Z, Dong Y, Scholz R, Neumann D, Zou MH. Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells. Circulation. 2008;117:952-962.
    • (2008) Circulation. , vol.117 , pp. 952-962
    • Xie, Z.1    Dong, Y.2    Scholz, R.3    Neumann, D.4    Zou, M.H.5
  • 50
    • 84878759308 scopus 로고    scopus 로고
    • Phosphorylation of serine 399 in LKB1 protein short form by protein kinase Cζ is required for its nucleocytoplasmic transport and consequent AMP-activated protein kinase (AMPK) activation
    • Zhu H, Moriasi CM, Zhang M, Zhao Y, Zou MH. Phosphorylation of serine 399 in LKB1 protein short form by protein kinase Cζ is required for its nucleocytoplasmic transport and consequent AMP-activated protein kinase (AMPK) activation. J Biol Chem. 2013;288:16495-16505.
    • (2013) J Biol Chem. , vol.288 , pp. 16495-16505
    • Zhu, H.1    Moriasi, C.M.2    Zhang, M.3    Zhao, Y.4    Zou, M.H.5


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.