Phosphorylation and activation of p70s6k by PDK1

被引：738

作者：

Pullen, N ^{[1
]}

Dennis, PB ^{[1
]}

Andjelkovic, M ^{[1
]}

Dufner, A ^{[1
]}

Kozma, SC ^{[1
]}

Hemmings, BA ^{[1
]}

Thomas, G ^{[1
]}

机构：

[1] Friedrich Miescher Inst, CH-4058 Basel, Switzerland

来源：

SCIENCE | 1998年 / 279卷 / 5351期

关键词：

D O I：

10.1126/science.279.5351.707

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Activation of the protein p70(s6k) by mitogens leads to increased translation of a family of messenger RNAs that encode essential components of the protein synthetic apparatus. Activation of the kinase requires hierarchical phosphorylation at multiple sites, culminating in the phosphorylation of the threonine in position 229 (Thr(229)), in the catalytic domain. The homologous site in protein kinase B (PKB), Thr(308), has been shown to be phosphorylated by the phosphoinositide-dependent protein kinase PDK1.A regulatory link between p70(s6k) and PKB was demonstrated, as PDK1 was found to selectively phosphorylate p70(s6k) at Thr(229). More importantly, PDK1 activated p70(s6k) in vitro and in vivo, whereas the catalytically inactive PDK1 blocked insulin-induced activation of p70(s6k).

引用

页码：707 / 710

页数：4

共 17 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] Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors
Andjelkovic, M
Jakubowicz, T
Cron, P
Ming, XF
Han, JW
Hemmings, BA
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) : 5699 - 5704
[4] PDGF-DEPENDENT AND INSULIN-DEPENDENT PP70(S6K) ACTIVATION MEDIATED BY PHOSPHATIDYLINOSITOL-3-OH KINASE
CHUNG, JK
GRAMMER, TC
LEMON, KP
KAZLAUSKAS, A
BLENIS, J
[J]. NATURE, 1994, 370 (6484) : 71 - 75
[5] 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
[6] Dennis P.B., UNPUB
[7] Dennis PB, 1996, MOL CELL BIOL, V16, P6242
[8] HANKS SK, 1995, PROTEIN KINASE FACTS
[9] Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70(S6k)
Jefferies, HBJ
Fumagalli, S
Dennis, PB
Reinhard, C
Pearson, RB
Thomas, G
[J]. EMBO JOURNAL, 1997, 16 (12) : 3693 - 3704
[10] Meyuhas Oded, 1996, V30, P363

← 1 2 →