The mouse Peutz-Jeghers syndrome gene Lkb1 encodes a nuclear protein kinase

The protein kinase gene LKB1 has recently been identified as the gene mutat ed in the Peutz-Jeghers cancer predisposition syndrome. This condition is c haracterized by inherited susceptibility to a range of cancers but in parti cular those of the gastrointestinal tract. Here we have characterized the m ouse Lkb1 gene. The mouse Lkb1 gene consists of 10 exons covering similar t o 15 kb in length, maps to mouse chromosome 10 and encodes a protein showin g strong sequence similarity to human LKB1. The 3' end of Lkb1 in the mouse is in very close proximity to the 3' end of an apparently unrelated gene R 29144/1 and it seems probable that overlapping transcripts of the two genes are produced. Using transfection of Lkb1 cDNAs we have shown that Lkb1 is most likely a nuclear protein and have defined a nuclear localization signa l within the protein sequence. Thus the defect in Peutz-Jeghers syndrome ma y directly result in changes in gene expression in the nucleus of target ce lls.