LKB1, the multitasking tumour suppressor kinase
- Correspondence to: Dr P A Marignani Dalhousie University, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Sir Charles Tupper Medical Building, Room 9S1, 5850 College Street, Halifax, Nova Scotia B3H-1X5, Canada; pmarignadal.ca
- Accepted 14 July 2004
Abstract
Mutations in the lkb1 gene are found in Peutz-Jeghers syndrome (PJS), with loss of heterozygosity or somatic mutations at the lkb1 locus, suggesting the gene product, the serine/threonine kinase LKB1, may function as a tumour suppressor. Patients with PJS are at a greater risk of developing cancers of epithelial tissue origin. It is widely accepted that the presence of hamartomatous polyps in PJS does not in itself lead to the development of malignancy. The signalling mechanisms that lead to these PJS related malignancies are not well understood. However, it is evident from the recent literature that LKB1 is a multitasking kinase, with unlimited potential in orchestrating cell activity. Thus far, LKB1 has been found to play a role in chromatin remodelling, cell cycle arrest, Wnt signalling, cell polarity, and energy metabolism, all of which may require the tumour suppressor function of this kinase and/or its catalytic activity.
- AMPK, 5′-AMP activated protein kinase
- Brg1, Brahma related gene 1
- Dvl, Dishevelled
- JPS, juvenile polyposis syndrome
- GSK-3β, glygogen synthase kinase 3β
- LIP1, LKB1 interacting protein
- par, partitioning-defective gene
- PJS, Peutz-Jeghers syndrome
- PKC, protein kinase C
- smad4, SMA and MAD related protein 4
- STRAD, STE20 related adaptor
- VEGF, vascular endothelial growth factor
- XEEK1, Xenopus laevis egg and embryonic kinase 1
