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Mol. Cells 2012; 34(4): 375-382

Published online October 31, 2012

https://doi.org/10.1007/s10059-012-0167-2

© The Korean Society for Molecular and Cellular Biology

The Nuclear Localization of Glycogen Synthase Kinase 3β Is Required Its Putative PY-Nuclear Localization Sequences

Sung Hwa Shin1, Eun Jeoung Lee1, Jaesun Chun2 , Sunghee Hyun3, Youg Il Kim1, and Sang Sun Kang1,4,*

1Department of Biology Education, Chungbuk National University, Cheongju 361-763, Korea, 2Department of Biology Education, Korea National University of Education, Cheongwon 363-791, Korea, 3Department of Pre-medicine, Eulji University School of Medicine, Daejeon 301-832, Korea, 4Biotechnology Research Institute, Chungbuk National University, Cheongju 361-763, Korea

Correspondence to : *Correspondence: jin95324@cbu.ac.kr

Received: June 25, 2012; Revised: August 21, 2012; Accepted: September 4, 2012

Abstract

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.

Keywords GSK-3beta, karyopherinbeta2, protein-protein interaction, PY NLS, subcellular localization

Article

Research Article

Mol. Cells 2012; 34(4): 375-382

Published online October 31, 2012 https://doi.org/10.1007/s10059-012-0167-2

Copyright © The Korean Society for Molecular and Cellular Biology.

The Nuclear Localization of Glycogen Synthase Kinase 3β Is Required Its Putative PY-Nuclear Localization Sequences

Sung Hwa Shin1, Eun Jeoung Lee1, Jaesun Chun2 , Sunghee Hyun3, Youg Il Kim1, and Sang Sun Kang1,4,*

1Department of Biology Education, Chungbuk National University, Cheongju 361-763, Korea, 2Department of Biology Education, Korea National University of Education, Cheongwon 363-791, Korea, 3Department of Pre-medicine, Eulji University School of Medicine, Daejeon 301-832, Korea, 4Biotechnology Research Institute, Chungbuk National University, Cheongju 361-763, Korea

Correspondence to:*Correspondence: jin95324@cbu.ac.kr

Received: June 25, 2012; Revised: August 21, 2012; Accepted: September 4, 2012

Abstract

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.

Keywords: GSK-3beta, karyopherinbeta2, protein-protein interaction, PY NLS, subcellular localization

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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