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Regulation of the Wnt signalling component PAR1A by the Peutz–Jeghers syndrome kinase LKB1


Loss-of-function mutations in the LKB1 (STK11) serine–threonine kinase gene cause Peutz–Jeghers syndrome, which is associated with inherited susceptibility to colorectal and other cancers. No downstream targets of LKB1 kinase activity have been identified. Here we show that LKB1 can direct the phosphorylation of the serine–threonine kinase PAR1A. The amino-acid residues phosphorylated as a result of LKB1 activity have been identified and phosphorylation at these residues is required for PAR1A kinase activity. PAR1A has previously been implicated as a positive regulator of the Wnt-βcatenin signalling pathway. We show here that LKB1 can modify transcription driven by the Wnt-regulated TCF response element, implicating LKB1 in a pathway known to play a key role in human colorectal tumorigenesis.

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expressed sequence tag


microtubule-associated protein


MAP/microtubule affinity-regulating kinase


Peutz–Jeghers syndrome


serine/threonine kinase


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JS was the recipient of an Institute of Cancer Research clinical research fellowship. This work was supported by Cancer Research UK and Breakthrough Breast Cancer. We thank Trevor Dale, Institute of Cancer Research, for providing reagents for the reporter assay.

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Correspondence to Alan Ashworth.

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Spicer, J., Rayter, S., Young, N. et al. Regulation of the Wnt signalling component PAR1A by the Peutz–Jeghers syndrome kinase LKB1. Oncogene 22, 4752–4756 (2003).

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