ABSTRACT
Glycogen synthase kinase-3ß(GSK-3ß), 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-3ß is associated with the karyopherin ß2 (Kap ß2) (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-3ß catalytic domain. Using a pull down approach, we observed that GSK-3ß physically interacts with Kap ß2 both in vivo and in vitro. Secondly, GSK-3ß and Kap ß2 were shown to be co-localized by confocal microscopy. The localization of GSK-3ß to the nuclear region was disrupted by putative Kap ß2 binding site mutation. Furthermore, in transient transfection assays, the Kap ß2 binding site mutant induced a substantial reduction in the in vivo serine/threonine phosphorylation of GSK-3ß, where- as the GSK-3ß wild type did not. Thus, our observations indicated that Kap ß2 imports GSK-3ß through its putative PY NLS motif from the cytoplasm to the nucleus and increases its kinase activity.
