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KMID : 0578320120340040375
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Molecules and Cells
2012 Volume.34 No. 4 p.375 ~ p.382
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The Nuclear Localization of Glycogen Synthase Kinase 3β Is Required Its Putative PY-Nuclear Localization Sequences
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Shin Sung-Hwa
Lee Eun-Jeoung
Chun Jae-Sun
Hyun Sung-Hee
Kim Youg-Il
Kang Sang-Sun
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Abstract
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Glycogen synthase kinase-3beta(GSK-3beta), which is a mem-ber of the serine/threonine kinase family, has been shown to be crucial for cellular survival, differentiation, and metabolism. Here, we present evidence that GSK-3? is associated with the karyopherin beta2 (Kapbeta2) (102-kDa), which functions as a substrate for transportation into the nucleus. A potential PY-NLS motif (109IVRLRYFFY117) was observed, which is similar with the consensus PY NLS motif (R/K/H)X2?5PY in the GSK-3beta catalytic domain. Using a pull down approach, we observed that GSK-3beta physically interacts with Kapbeta2 both in vivo and in vitro. Secondly, GSK-3beta and Kap beta 2 were shown to be co-localized by confocal microscopy. The localization of GSK-3beta to the nuclear region was disrupted by putative Kapbeta2 binding site mutation. Furthermore, in transient transfection assays, the Kapbeta2 binding site mutant induced a substantial reduction in the in vivo serine/threonine phosphorylation of GSK-3beta, where- as the GSK-3beta wild type did not. Thus, our observations indicated that Kapbeta2 imports GSK-3beta through its putative PY NLS motif from the cytoplasm to the nucleus and increases its kinase activity.
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KEYWORD
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GSK-3beta, karyopherinbeta2, protein-protein interaction, PY NLS, subcellular localization
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