The nuclear localization of glycogen synthase kinase 3? is required its putative PY-nuclear localization sequences.

ABSTRACT: Glycogen synthase kinase-3?(GSK-3?), which is a member 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 ?2 (Kap ?2) (102-kDa), which functions as a substrate for transportation into the nucleus. A potential PY-NLS motif ((109)IVRLRYFFY(117)) was observed, which is similar with the consensus PY NLS motif (R/K/H)X(2-5)PY in the GSK-3? catalytic domain. Using a pull down approach, we observed that GSK-3? physically interacts with Kap ?2 both in vivo and in vitro. Secondly, GSK-3? and Kap ?2 were shown to be co-localized by confocal microscopy. The localization of GSK-3? to the nuclear region was disrupted by putative Kap ?2 binding site mutation. Furthermore, in transient transfection assays, the Kap ?2 binding site mutant induced a substantial reduction in the in vivo serine/threonine phosphorylation of GSK-3?, where- as the GSK-3? wild type did not. Thus, our observations indicated that Kap ?2 imports GSK-3? through its putative PY NLS motif from the cytoplasm to the nucleus and increases its kinase activity.

SUBMITTER: Shin SH 

PROVIDER: S-EPMC3887767 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature