Further evidence that the inhibition of glycogen synthase kinase-3 beta by IGF-1 is mediated by PDK1/PKB-induced phosphorylation of Ser-9 and not by dephosphorylation of Tyr-216

被引：211

作者：

Shaw, M

Cohen, P

Alessi, DR

机构：

[1] MRC Protein Phosphorylation Unit, Dept. of Biochem., Univ. of Dundee

来源：

FEBS LETTERS | 1997年 / 416卷 / 03期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

insulin; insulin-like growth factor-1; protein kinase B; glycogen synthase kinase-3; glycogen synthase; 3-phosphoinositide-dependent protein kinase;

D O I：

10.1016/S0014-5793(97)01235-0

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：

293 cells were transfected with mild-type GSK3 beta (WT-GSK3 beta) or a mutant in which the PKB phosphorylation site (Ser-9) mas altered to Ala (A9-GSK3 beta), Upon stimulation with IGF-1 or insulin, WT-GSK3 beta was inhibited 75% or 60%, respectively, whereas the activity of the A9-GSK3 beta mutant was unaffected, Incubation of WT-GSK3 beta with PP2A(1) (a Ser/Thr-specific phosphatase) completely reversed the IGF-1- or insulin-induced inhibition. IGF-1 stimulation did not induce any tyrosine dephosphorylation of WT-GSK3 beta or A9-GSK3 beta, Coexpression of WT-GSK3 beta in 293 cells with either PKB alpha (also known as AKT) or PDK1 (the 'upstream' activator of PKB) mimicked the IGF-1- or insulin-induced phosphorylation of Ser-9 and inactivation of GSK3 beta. (C) 1997 Federation of European Biochemical Societies.

引用

页码：307 / 311

页数：5

共 24 条

[1] Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha
Alessi, DR
James, SR
Downes, CP
Holmes, AB
Gaffney, PRJ
Reese, CB
Cohen, P
[J]. CURRENT BIOLOGY, 1997, 7 (04) : 261 - 269
[2] 3-phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase
Alessi, DR
Deak, M
Casamayor, A
Caudwell, FB
Morrice, N
Norman, DG
Gaffney, P
Reese, CB
MacDougall, CN
Harbison, D
Ashworth, A
Bownes, M
[J]. CURRENT BIOLOGY, 1997, 7 (10) : 776 - 789
[3] Mechanism of activation of protein kinase B by insulin and IGF-1
Alessi, DR
Andjelkovic, M
Caudwell, B
Cron, P
Morrice, N
Cohen, P
Hemmings, BA
[J]. EMBO JOURNAL, 1996, 15 (23) : 6541 - 6551
[4] ANDERSSON S, 1989, J BIOL CHEM, V264, P8222
[5] The Tenth Datta Lecture - PDK1, one of the missing links in insulin signal transduction?
Cohen, P
Alessi, DR
Cross, DAE
[J]. FEBS LETTERS, 1997, 410 (01) : 3 - 10
[6] Insulin activates protein kinase B, inhibits glycogen synthase kinase-3 and activates glycogen synthase by rapamycin-insensitive pathways in skeletal muscle and adipose tissue
Cross, DAE
Watt, PW
Shaw, M
vanderKaay, J
Downes, CP
Holder, JC
Cohen, P
[J]. FEBS LETTERS, 1997, 406 (1-2) : 211 - 215
[7] INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B
CROSS, DAE
ALESSI, DR
COHEN, P
ANDJELKOVICH, M
HEMMINGS, BA
[J]. NATURE, 1995, 378 (6559) : 785 - 789
[8] GLYCOGEN-SYNTHASE KINASE-3 FROM RABBIT SKELETAL-MUSCLE - SEPARATION FROM CYCLIC-AMP-DEPENDENT PROTEIN-KINASE AND PHOSPHORYLASE-KINASE
EMBI, N
RYLATT, DB
COHEN, P
[J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1980, 107 (02): : 519 - 527
[9] Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons
Hong, M
Lee, VMY
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (31) : 19547 - 19553
[10] MODULATION OF THE GLYCOGEN-SYNTHASE KINASE-3 FAMILY BY TYROSINE PHOSPHORYLATION
HUGHES, K
NIKOLAKAKI, E
PLYTE, SE
TOTTY, NF
WOODGETT, JR
[J]. EMBO JOURNAL, 1993, 12 (02) : 803 - 808

← 1 2 3 →