Nuclear Translocation of Cell Adhesion Kinase β/Proline-rich Tyrosine Kinase 2

Abstract

Cell adhesion kinase β (CAKβ/PYK2) is a protein-tyrosine kinase of the focal adhesion kinase (FAK) family. Whereas FAK predominantly localizes at focal adhesions, CAK β localizes at the perinuclear region in fibroblasts. Here we expressed in cultured cells two point mutants of CAKβ, P717A and P859A, each of which had lost one of its two PXXP motifs, the ligand sequence for SH3 domains, found at the CAKβ C-terminal region. We observed a remarkable change in the subcellular distribution of the P859A mutant; while that of the P717A mutant was the same as the wild type. The P859A mutant localized exclusively in the cell nucleus in all cell lines examined. Wild-type CAKβ also accumulated in the nucleus when cells were treated with an inhibitor of the nuclear export of proteins. These results indicate that CAK β shuttles between the cytoplasm and the nucleus. On nuclear accumulation of P859A-CAKβ, a CAKβ-binding protein, Hic-5, also accumulated in the nucleus. P859A-CAKβ and co-expressed Hic-5 formed nuclear speckles, in which one other CAK β-binding protein, p130^Cas, was also concentrated. These findings on nuclear translocation of CAK β imply that CAKβ may regulate nuclear processes such as transcription, particularly because Hic-5 was recently shown to be a coactivator of nuclear receptors.