QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 12 September 2006
doi: 10.1242/jcs.03169

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.03169v1 119/19/4002    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Kiyama, R. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Kiyama, R.

Nucleo-cytoplasmic shuttling of human Kank protein accompanies intracellular translocation of ß-catenin

Signaling Molecules Research Laboratory, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan

^* Author for correspondence (e-mail: kiyama.r{at}aist.go.jp)

Accepted 14 July 2006

The human Kank protein has a role in controlling the formation of the cytoskeleton by regulating actin polymerization. Besides the cytoplasmic localization as reported before, we observed the nuclear localization of Kank in OS-RC-2 cells. To uncover the mechanism behind this phenomenon, we focused on the nuclear localization signal (NLS) and the nuclear export signal (NES). We found one NLS (NLS1) and two NESs (NES1 and NES2) in the N-terminal region of Kank-L that were absent in Kank-S, and another NLS (NLS2) and NES (NES3) in the common region. These signals were active as mutations introduced into them abolished the nuclear import (for NLS1 and NLS2) or the nuclear export (for NES1 to NES3) of Kank. The localization of Kank in the cells before and after treatment with leptomycin B suggested that the transportation of Kank from the nucleus to the cytoplasm was mediated by a CRM1-dependent mechanism. TOPFLASH reporter assays revealed a positive relationship between the nuclear import of Kank and the activation of ß-catenin-dependent transcription. Kank can bind to ß-catenin and regulate the subcellular distribution of ß-catenin. Based on the findings shown here, we propose that Kank has multiple functions in the cells and plays different roles in the cytoplasm and the nucleus.

Key words: Kank, ß-catenin, Nucleo-cytoplasmic shuttling, Nuclear localization signal, Nuclear export signal