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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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Glycogen synthase kinase-3β (GSK3β) is a highly conserved kinase that functions as a key regulator of many cellularsignalling pathways. Unlike other kinases, GSK3β transduces signalling via inhibition by upstream kinases or factors. Inthe Wnt/β-catenin signalling pathway, the Wnt coreceptor LRP6/5 serves as a direct inhibitor of GSK3β when the PPPSPmotif in LRP6/5 is phosphorylated upon Wnt activation. We constructed a chimeric protein composed of the PPPSP motifand the mouse GSK3β to determine the crystal structure of GSK3β in complex with the phosphorylated LRP6 peptide. Thecrystal structure of the chimeric protein was determined at a 2.6 A resolution using protein expressed in insect cells. OurGSK3β structure was compared with other previously determined structures. The dimeric assembly provided implicationsfor the functional significance of the kinase dimer. The phospho-Ser/Thr binding pocket contained a malonate moleculederived from the crystallization solution. Our findings will increase our understanding of the structure of this multifunctionalkinase, which is a potential therapeutic target for diabetes and neurological disorders.
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참고문헌 (26)
참고문헌 신청
Ali, A. / 2001 / Glycogen synthase kinase-3 : properties, functions, and regulation / Chem Rev 101:2527~2540
Bax, B. / 2001 / The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation / Structure 9:1143~1152
Cervenka, I. / 2011 / Mitogen-activated protein kinases promote WNT/beta-catenin signaling via phosphorylation of LRP6 / Mol Cell Biol 31:179~189
Chen, M. / 2009 / G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway / J Biol Chem 284:35040~35048
Cohen, P. / 1993 / Dissection of the protein phosphorylation cascades involved in insulin and growth factor action / Biochem Soc Trans 21(Pt 3):555~567
Bax, B. / 2001 / The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation / Structure 9:1143~1152
Cervenka, I. / 2011 / Mitogen-activated protein kinases promote WNT/beta-catenin signaling via phosphorylation of LRP6 / Mol Cell Biol 31:179~189
Chen, M. / 2009 / G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway / J Biol Chem 284:35040~35048
Cohen, P. / 1993 / Dissection of the protein phosphorylation cascades involved in insulin and growth factor action / Biochem Soc Trans 21(Pt 3):555~567
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