LKB1, a protein kinase regulating cell proliferation and polarity

被引:147
作者
Boudeau, J [1 ]
Sapkota, G [1 ]
Alessi, DR [1 ]
机构
[1] Univ Dundee, MRC Protein Phosphorylat Unit, Dundee DD1 5EH, Scotland
关键词
tumor suppressor; cancer; cell growth; Peutz-Jeghers syndrome;
D O I
10.1016/S0014-5793(03)00642-2
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
LKB1 is a serine-threonine protein kinase mutated in patients with an autosomal dominantly inherited cancer syndrome predisposing to multiple benign and malignant tumours, termed Peutz-Jeghers syndrome. Since its discovery in 1998, much research has focused on identification and characterisation of its cellular roles and analysing how LKB1 might be regulated. In this review we discuss exciting recent advances indicating that LKB1 functions as a tumour suppressor perhaps by controlling cell polarity. We also outline the current understanding of the molecular mechanisms by which LKB1 is regulated in vivo, through interaction with other proteins as well as by protein phosphorylation and prenylation. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:159 / 165
页数:7
相关论文
共 72 条
[1]  
Avizienyte E, 1998, CANCER RES, V58, P2087
[2]   LKB1 somatic mutations in sporadic tumors [J].
Avizienyte, E ;
Loukola, A ;
Roth, S ;
Hemminki, A ;
Tarkkanen, M ;
Salovaara, R ;
Arola, J ;
Bützow, R ;
Husgafvel-Pursiainen, K ;
Kokkola, A ;
Järvinen, H ;
Aaltonen, LA .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (03) :677-681
[3]  
BAAS AF, 2003, IN PRESS EMBO J
[4]   Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation [J].
Bardeesy, N ;
Sinha, M ;
Hezel, AF ;
Signoretti, S ;
Hathaway, NA ;
Sharpless, NE ;
Loda, M ;
Carrasco, DR ;
DePinho, RA .
NATURE, 2002, 419 (6903) :162-167
[5]  
BLUMER JB, 2003, IN PRESS J BIOL CHEM
[6]  
Boardman LA, 2000, HUM MUTAT, V16, P23, DOI 10.1002/1098-1004(200007)16:1<23::AID-HUMU5>3.0.CO
[7]  
2-M
[8]   Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability [J].
Boudeau, J ;
Deak, M ;
Lawlor, MA ;
Morrice, NA ;
Alessi, DR .
BIOCHEMICAL JOURNAL, 2003, 370 :849-857
[9]   Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2 [J].
Buchet-Poyau, K ;
Mehenni, H ;
Radhakrishna, U ;
Antonarakis, SE .
CYTOGENETIC AND GENOME RESEARCH, 2002, 97 (3-4) :171-178
[10]   The phosphoinositide 3-kinase pathway [J].
Cantley, LC .
SCIENCE, 2002, 296 (5573) :1655-1657