Abstract:
: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-betacatenin 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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Spicer J,Rayter S,Young N,Elliott R,Ashworth A,Smith Ddoi
10.1038/sj.onc.1206669subject
Has Abstractpub_date
2003-07-24 00:00:00pages
4752-6issue
30eissn
0950-9232issn
1476-5594pii
1206669journal_volume
22pub_type
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