Nucleo-cytoplasmic shuttling of human Kank protein accompanies intracellular translocation of beta-catenin.
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 beta-catenin-dependent transcription. Kank can bind to beta-catenin and regulate the subcellular distribution of beta-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.
Wang
Yong
Y
Signaling Molecules Research Laboratory, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Kakinuma
Naoto
N
Zhu
Yun
Y
Kiyama
Ryoiti
R
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000737:chemistry; D021382:Protein Sorting Signals; D021381:Protein Transport / Q000502:physiology*; D014018:Tissue Distribution / Q000187:drug effects; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D005231:Fatty Acids, Unsaturated; C467739:KANK1 protein, human; D019913:Nuclear Localization Signals; D021382:Protein Sorting Signals; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; C038753:leptomycin B