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

被引：83

作者：

Spicer, J ^{[1
]}

Rayter, S ^{[1
]}

Young, N ^{[1
]}

Elliott, R ^{[1
]}

Ashworth, A ^{[1
]}

Smith, D ^{[1
]}

机构：

[1] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Canc Res UK Gene Funct & Regulat Grp, London SW3 6JB, England

来源：

ONCOGENE | 2003年 / 22卷 / 30期

关键词：

cancer susceptibility; Peutz-Jeghers syndrome; Wnt signalling; colorectal cancer; protein kinase;

D O I：

10.1038/sj.onc.1206669

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4752 / 4756

页数：5

共 27 条

[1] Immunolocalisation of β catenin in intestinal polyps of Peutz-Jeghers and juvenile polyposis syndromes [J].