Journal Article

The Mouse Peutz-Jeghers Syndrome Gene <i>Lkbl</i> Encodes a Nuclear Protein Kinase

Darrin P. Smith, James Spicer, Amanda Smith, Sally Swift and Alan Ashworth

in Human Molecular Genetics

Volume 8, issue 8, pages 1479-1485
Published in print August 1999 | ISSN: 0964-6906
Published online August 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.8.1479
The Mouse Peutz-Jeghers Syndrome Gene Lkbl Encodes a Nuclear Protein Kinase

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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 Lkbl gene. The mouse Lkbl gene consists of 10 exons covering ∼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 Lkbl 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.

Journal Article.  4572 words.  Illustrated.

Subjects: Genetics and Genomics

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