Identification and characterization of the nuclear import and export signals of the mammalian Ste20‐like protein kinase 3

• Published in: FEBS letters 2004-08, Vol.572 (1-3), p.41-45
• Main Authors: Lee, Wan-Shu, Hsu, Chiung-Yueh, Wang, Pei-Ling, Huang, Chi-Ying Fred, Chang, Chia-Hua, Yuan, Chiun-Jye
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus - drug effects; Active Transport, Cell Nucleus - physiology; Amino Acid Sequence; Animals; Base Sequence; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cloning, Molecular; DNA Primers; Fatty Acids, Unsaturated - pharmacology; Genes, Reporter; GFP, green fluorescence protein; Green Fluorescent Proteins; HeLa Cells; Humans; LMB, leptomycin B; Luminescent Proteins - metabolism; Mammals; Microscopy, Fluorescence; Molecular Sequence Data; Mst, mammalian Ste20-like protein kinase; Mst3; NES, nuclear exporting signal; NLS, nuclear localization sequence; Nuclear exporting signal; Nuclear localization sequence; Nuclear trafficking; Peptide Fragments - chemistry; Protein-Serine-Threonine Kinases - metabolism; Recombinant Fusion Proteins - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Ste20
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.07.007

Mst3, a human Ste20‐like protein kinase, has been recently demonstrated to undergo a caspase‐mediated cleavage during apoptosis. The proteolytic cleavage of the C‐terminus of Mst3 caused nuclear translocation of its kinase domain. This work provides evidence that Mst3 may contain a bipartite‐like nuclear localization sequence (NLS) at the C‐terminus of its kinase domain (residues 278–292). The removal of NLS from the kinase domain of Mst3 led to the cytoplasmic accumulation of EGFP‐Mst3Δ277. The presence of nuclear exporting signals in the Mst3 was also demonstrated by leptomycin B‐treatment and serial deletion of the C‐terminal regulatory domain of Mst3. A nuclear export signal was also postulated to be in the regions of amino acids 335–386. In conclusion, Mst3 contains both NLS and NES signals, which may cooperate to control the subcellular distribution of Mst3.