Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B

被引：1055

作者：

Stokoe, D

Stephens, LR

Copeland, T

Gaffney, PRJ

Reese, CB

Painter, GF

Holmes, AB

McCormick, F

Hawkins, PT

机构：

[1] ONYX PHARMACEUT,RICHMOND,CA 94806

[2] BABRAHAM INST,CAMBRIDGE CB2 4AT,ENGLAND

[3] NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702

[4] UNIV LONDON KINGS COLL,DEPT CHEM,LONDON WC2R 2LS,ENGLAND

[5] UNIV CAMBRIDGE,DEPT CHEM,CAMBRIDGE CB2 3RA,ENGLAND

来源：

SCIENCE | 1997年 / 277卷 / 5325期

关键词：

D O I：

10.1126/science.277.5325.567

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：

Protein kinase B (PKB) is a proto-oncogene that is activated in signaling pathways initiated by phosphoinositide 3-kinase. Chromatographic separation of brain cytosol revealed a kinase activity that phosphorylated and activated PKB only in the presence of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P-3]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P-3 was determined to have a dual role: its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase and it directly activated the upstream kinase.

引用

页码：567 / 570

页数：4

共 23 条

[1] AHMED NN, 1993, ONCOGENE, V8, P1957
[2] 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
[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] BELLACOSA A, 1993, ONCOGENE, V8, P745
[5] PROTEIN-KINASE-B (C-AKT) IN PHOSPHATIDYLINOSITOL-3-OH INASE SIGNAL-TRANSDUCTION
BURGERING, BMT
COFFER, PJ
[J]. NATURE, 1995, 376 (6541) : 599 - 602
[6] 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
[7] Akt is a direct target of the phosphatidylinositol 3-kinase - Activation by growth factors, v-src and v-Ha-ras, in Sf9 and mammalian cells
Datta, K
Bellacosa, A
Chan, TO
Tsichlis, PN
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (48) : 30835 - 30839
[8] Constitutive activation of protein kinase B and phosphorylation of p47(phox) by membrane-targeted phosphoinositide 3-kinase
Didichenko, SA
Tilton, B
Hemmings, BA
BallmerHofer, K
Thelen, M
[J]. CURRENT BIOLOGY, 1996, 6 (10) : 1271 - 1278
[9] THE PROTEIN-KINASE ENCODED BY THE AKT PROTOONCOGENE IS A TARGET OF THE PDGF-ACTIVATED PHOSPHATIDYLINOSITOL 3-KINASE
FRANKE, TF
YANG, SI
CHAN, TO
DATTA, K
KAZLAUSKAS, A
MORRISON, DK
KAPLAN, DR
TSICHLIS, PN
[J]. CELL, 1995, 81 (05) : 727 - 736
[10] PI3K: Downstream AKTion blocks apoptosis
Franke, TF
Kaplan, DR
Cantley, LC
[J]. CELL, 1997, 88 (04) : 435 - 437

← 1 2 3 →