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

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

Oncogene

journal_title

Oncogene

authors

Spicer J,Rayter S,Young N,Elliott R,Ashworth A,Smith D

doi

10.1038/sj.onc.1206669

subject

Has Abstract

pub_date

2003-07-24 00:00:00

pages

4752-6

issue

30

eissn

0950-9232

issn

1476-5594

pii

1206669

journal_volume

22

pub_type

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