Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB

被引：83

作者：

Maag, David ^{[1
]}

Maxwell, Micah J. ^{[1
]}

Hardesty, Douglas A. ^{[4
]}

Boucher, Katie L. ^{[4
]}

Choudhari, Namrata ^{[4
]}

Hanno, Adam G. ^{[4
]}

Ma, Jenny F. ^{[4
]}

Snowman, Adele S. ^{[1
]}

Pietropaoli, Joseph W. ^{[1
]}

Xu, Risheng ^{[1
,2
]}

Storm, Phillip B. ^{[4
]}

Saiardi, Adolfo ^{[5
,6
]}

Snyder, Solomon H. ^{[1
,2
,3
]}

Resnick, Adam C. ^{[4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA

[4] Childrens Hosp Philadelphia, Dept Neurosurg, Philadelphia, PA 19104 USA

[5] UCL, MRC, Mol Cell Biol Lab, Cell Biol Unit, London WC1E 6BT, England

[6] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 04期

关键词：

signal transduction; cancer; HEXAKISPHOSPHATE KINASE-2; PHOSPHATE MULTIKINASE; HUMAN HOMOLOG; PROTEIN; PATHWAY; PENTAKISPHOSPHATE; PYROPHOSPHORYLATION; PYROPHOSPHATES; LOCALIZATION; INHIBITOR;

D O I：

10.1073/pnas.1017831108

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：

The second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3), formed by the p110 family of PI3-kinases, promotes cellular growth, proliferation, and survival, in large part by activating the protein kinase Akt/PKB. We show that inositol polyphosphate multikinase (IPMK) physiologically generates PIP3 as well as water soluble inositol phosphates. IPMK deletion reduces growth factor-elicited Akt signaling and cell proliferation caused uniquely by loss of its PI3-kinase activity. Inhibition of p110 PI3-kinases by wortmannin prevents IPMK phosphorylation and activation. Thus, growth factor stimulation of Akt signaling involves PIP3 generation through the sequential activations of the p110 PI3-kinases and IPMK. As inositol phosphates inhibit Akt signaling, IPMK appears to act as a molecular switch, inhibiting or stimulating Akt via its inositol phosphate kinase or PI3-kinase activities, respectively. Drugs regulating IPMK may have therapeutic relevance in influencing cell proliferation.

引用

页码：1391 / 1396

页数：6

共 50 条

[41] PI3-kinase, the key for bugs to get in?
Lauvau, Gregoire
JOURNAL OF EXPERIMENTAL MEDICINE, 2015, 212 (02): : 127 - 127
[42] Glimepiride induces proliferation and differentiation of rat osteoblasts via the PI3-kinase/Akt pathway
Ma, Pan
Gu, Bin
Ma, Junli
E, Lingling
Wu, Xia
Cao, Junkai
Liu, Hongchen
METABOLISM-CLINICAL AND EXPERIMENTAL, 2010, 59 (03): : 359 - 366
[43] Biliverdin reductase mediates hypoxia-induced EMT via PI3-Kinase and Akt
Zeng, Rui
Yao, Ying
Han, Min
Zhao, Xiaoqin
Liu, Xiao-Cheng
Wei, Juncheng
Luo, Yun
Zhang, Juan
Zhou, Jianfeng
Wang, Shixuan
Ma, Ding
Xu, Gang
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2008, 19 (02): : 380 - 387
[44] Hydrogen peroxide-mediated phosphorylation of ERK1/2, Akt/PKB and JNK in cortical neurones:: dependence on Ca2+ and PI3-kinase
Crossthwaite, AJ
Hasan, S
Williams, RJ
JOURNAL OF NEUROCHEMISTRY, 2002, 80 (01) : 24 - 35
[45] PTEN and the PI3-Kinase Pathway in Cancer
Chalhoub, Nader
Baker, Suzanne J.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2009, 4 : 127 - 150
[46] A TARGET FOR PHOSPHOINOSITIDE 3-KINASE - AKT/PKB
BOS, JL
TRENDS IN BIOCHEMICAL SCIENCES, 1995, 20 (11) : 441 - 442
[47] HBP1 is a new target of the PI3-kinase - PKB - FOXO pathway downstream growth factor receptors
de Brachene, A. Coomans
Bollaert, E.
Serra, A. de Rocca
Eijkelenboom, A.
Burgering, B.
Coffer, P.
Essaghir, A.
Demoulin, J. -B.
FEBS JOURNAL, 2014, 281 : 470 - 470
[48] Regulation of PI(3)K/Akt signalling and cellular transformation by inositol polyphosphate 4-phosphatase-1
Ivetac, Ivan
Gurung, Rajendra
Hakim, Sandra
Horan, Kristy A.
Sheffield, David A.
Binge, Lauren C.
Majerus, Philip W.
Tiganis, Tony
Mitchell, Christina A.
EMBO REPORTS, 2009, 10 (05) : 487 - 493
[49] Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa
Chung, CY
Potikyan, G
Firtel, RA
MOLECULAR CELL, 2001, 7 (05) : 937 - 947
[50] Protein Kinase B (PKB/Akt), a Key Mediator of the PI3K Signaling Pathway
Fayard, Elisabeth
Xue, Gongda
Parcellier, Arnaud
Bozulic, Lana
Hemmings, Brian A.
PHOSPHOINOSITIDE 3-KINASE IN HEALTH AND DISEASE, VOL 1, 2010, 346 : 31 - 56

← 1 2 3 4 5 →