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Human Molecular Genetics, Vol 8, 1479-1485, Copyright © 1999 by Oxford University Press

ARTICLES

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

DP Smith, J Spicer, A Smith, S Swift and A Ashworth
Section of Gene Function and Regulation, Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.

The protein kinase gene LKB1 has recently been identified as the gene mutated in the Peutz-Jeghers cancer predisposition syndrome. This condition is characterized by inherited susceptibility to a range of cancers but in particular those of the gastrointestinal tract. Here we have characterized the mouse Lkb1 gene. The mouse Lkb1 gene consists of 10 exons covering approximately 15 kb in length, maps to mouse chromosome 10 and encodes a protein showing 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 R29144/1 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 signal within the protein sequence. Thus the defect in Peutz-Jeghers syndrome may directly result in changes in gene expression in the nucleus of target cells.
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