Glycogen synthase kinase 3: A key regulator of cellular fate

被引:328
作者
Forde, J. E. [1 ]
Dale, T. C. [1 ]
机构
[1] Cardiff Sch Biosci, Cardiff CF10 3US, Wales
基金
英国生物技术与生命科学研究理事会;
关键词
glycogen synthase kinase-3 (GSK-3); mechanism of action; inhibitors; signalling; disease; kinase; regulation;
D O I
10.1007/s00018-007-7045-7
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
The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified as a key regulator of insulin-dependent glycogen synthesis. GSK-3 was subsequently shown to function in a wide range of cellular processes including differentiation, growth, motility and apoptosis. Aberrant regulation of GSK-3 has been implicated in a range of human pathologies including Alzheimer's disease, non-insulin dependent diabetes mellitus ( NIDDM) and cancer. As a consequence, the regulation of GSK-3 and the therapeutic potential of GSK-3 inhibitors have become key areas of investigation. This review will focus on the mechanisms of GSK-3 regulation, with emphasis on modulation by upstream signals, control of substrate specificity and GSK-3 localisation. The details of these mechanisms will be discussed in the context of specific signalling pathways.
引用
收藏
页码:1930 / 1944
页数:15
相关论文
共 139 条
[1]   Glycogen synthase kinase-3: Properties, functions, and regulation [J].
Ali, A ;
Hoeflich, KP ;
Woodgett, JR .
CHEMICAL REVIEWS, 2001, 101 (08) :2527-2540
[2]   Axin-mediated CKI phosphorylation of β-catenin at Ser 45:: a molecular switch for the Wnt pathway [J].
Amit, S ;
Hatzubai, A ;
Birman, Y ;
Andersen, JS ;
Ben-Shushan, E ;
Mann, M ;
Ben-Neriah, Y ;
Alkalay, I .
GENES & DEVELOPMENT, 2002, 16 (09) :1066-1076
[3]   Yeast glycogen synthase kinase 3 is involved in protein degradation in cooperation with Bul1, Bul2, and Rsp5 [J].
Andoh, T ;
Hirata, Y ;
Kikuchi, A .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (18) :6712-6720
[4]   Proteolysis that is inhibited by Hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor [J].
AzaBlanc, P ;
RamirezWeber, FA ;
Laget, MP ;
Schwartz, C ;
Kornberg, TB .
CELL, 1997, 89 (07) :1043-1053
[5]   The structure of phosphorylated GSK-3β complexed with a peptide, FRATtide, that inhibits β-catenin phosphorylation [J].
Bax, B ;
Carter, PS ;
Lewis, C ;
Guy, AR ;
Bridges, A ;
Tanner, R ;
Pettman, G ;
Mannix, C ;
Culbert, AA ;
Brown, MJB ;
Smith, DG ;
Reith, AD .
STRUCTURE, 2001, 9 (12) :1143-1152
[6]   Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3 [J].
Beals, CR ;
Sheridan, CM ;
Turck, CW ;
Gardner, P ;
Crabtree, GR .
SCIENCE, 1997, 275 (5308) :1930-1933
[7]   EMBRYONIC LETHALITY AND LIVER DEGENERATION IN MICE LACKING THE RELA COMPONENT OF NF-KAPPA-B [J].
BEG, AA ;
SHA, WC ;
BRONSON, RT ;
GHOSH, S ;
BALTIMORE, D .
NATURE, 1995, 376 (6536) :167-170
[8]   Glycogen synthase kinase 3: a drug target for CNS therapies [J].
Bhat, RV ;
Haeberlein, SLB ;
Avila, J .
JOURNAL OF NEUROCHEMISTRY, 2004, 89 (06) :1313-1317
[9]   Glycogen synthase kinase-3β facilitates staurosporine- and heat shock-induced apoptosis -: Protection by lithium [J].
Bijur, GN ;
De Sarno, P ;
Jope, RS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (11) :7583-7590
[10]   ACTIVATION OF PROTEIN-KINASE-C DECREASES PHOSPHORYLATION OF C-JUN AT SITES THAT NEGATIVELY REGULATE ITS DNA-BINDING ACTIVITY [J].
BOYLE, WJ ;
SMEAL, T ;
DEFIZE, LHK ;
ANGEL, P ;
WOODGETT, JR ;
KARIN, M ;
HUNTER, T .
CELL, 1991, 64 (03) :573-584