PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K

被引：125

作者：

Malek, Mouhannad ^{[1
]}

Kielkowska, Anna ^{[1
]}

Chessa, Tamara ^{[1
]}

Anderson, Karen E. ^{[1
]}

Barneda, David ^{[1
,5
]}

Pir, Pinar ^{[1
]}

Nakanishi, Hiroki ^{[2
]}

Eguchi, Satoshi ^{[2
]}

Koizumi, Atsushi ^{[3
]}

Sasaki, Junko ^{[2
]}

Juvin, Veronique ^{[1
]}

Kiselev, Vladimir Y. ^{[1
]}

Niewczas, Izabella ^{[1
]}

Gray, Alexander ^{[4
]}

Valayer, Alexandre ^{[1
]}

Spensberger, Dominik ^{[1
]}

Imbert, Marine ^{[1
]}

Felisbino, Sergio ^{[6
]}

Habuchi, Tomonori ^{[3
]}

Beinke, Soren ^{[7
]}

Cosulich, Sabina ^{[5
]}

Le Novere, Nicolas ^{[1
]}

Sasaki, Takehiko ^{[2
]}

Clark, Jonathan ^{[1
]}

Hawkins, Phillip T. ^{[1
]}

Stephens, Len R. ^{[1
]}

机构：

[1] Babraham Inst, Signalling Programme, Cambridge, England

[2] Akita Univ, Grad Sch Med, Dept Med Biol, 1-1-1 Hondo, Akita, Japan

[3] Akita Univ, Grad Sch Med, Dept Urol, 1-1-1 Hondo, Akita, Japan

[4] Univ Dundee, Sch Life Sci, Dow St, Dundee, Scotland

[5] AstraZeneca R&D Cambridge, CRUK Cambridge Inst, Cambridge, England

[6] Sao Paulo State Univ UNESP, Dept Morphol, Inst Biosci Botucatu, Botucatu, SP, Brazil

[7] GlaxoSmithKline, Refractory Resp Inflammat Discovery Performance U, Stevenage, Herts, England

来源：

MOLECULAR CELL | 2017年 / 68卷 / 03期

基金：

英国生物技术与生命科学研究理事会; 日本学术振兴会; 英国惠康基金;

关键词：

TUMOR-SUPPRESSOR; STIMULATED SYNTHESIS; INPP4B; GROWTH; PHOSPHATASE; PATHWAY; CELLS; PHOSPHOINOSITIDES; ROLES; GENE;

D O I：

10.1016/j.molcel.2017.09.024

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 PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P-3. PI(3,4,5)P-3 can be dephosphorylated by 3-or 5-phosphatases, the latter producing PI(3,4)P-2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P-3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4) P-2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4) P-2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P-2 4-phosphatase, leads to synergistic accumulation of PI(3,4) P-2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P-2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P-2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4) P-2 in the phenotype caused by loss-of-function mutations or deletions in PTEN.

引用

页码：566 / +

页数：25

共 50 条

[41] Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2
Jiangqing Dong
Ximing Du
Huan Wang
Jue Wang
Chang Lu
Xiang Chen
Zhiwen Zhu
Zhipu Luo
Li Yu
Andrew J. Brown
Hongyuan Yang
Jia-Wei Wu
Nature Communications, 10
[42] Regulation of PTEN translation by PI3K signaling maintains pathway homeostasis
Mukherjee, Radha
Vanaja, Kiran Gireesan
Boyer, Jacob A.
Qiu, Juan
Chen, Xiaoping
de Stanchina, Elisa
Chandarlapaty, Sarat
Levchenko, Andre
Rosen, Neal
CANCER RESEARCH, 2020, 80 (16)
[43] LncRNAs and PTEN/PI3K signaling: A symphony of regulation in cancer biology
Almalki, Waleed Hassan
PATHOLOGY RESEARCH AND PRACTICE, 2023, 249
[44] Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2
Dong, Jiangqing
Du, Ximing
Wang, Huan
Wang, Jue
Lu, Chang
Chen, Xiang
Zhu, Zhiwen
Luo, Zhipu
Yu, Li
Brown, Andrew J.
Yang, Hongyuan
Wu, Jia-Wei
NATURE COMMUNICATIONS, 2019, 10 (1)
[45] PI3K/AKT signaling regulates bioenergetics in immortalized hepatocytes
Li, Chen
Li, Yang
He, Lina
Agarwal, Amit R.
Zeng, Ni
Cadenas, Enrique
Stiles, Bangyan L.
FREE RADICAL BIOLOGY AND MEDICINE, 2013, 60 : 29 - 40
[46] PI3K/mTOR signaling regulates prostatic branching morphogenesis
Ghosh, Susmita
Lau, Hiu
Simons, Brian W.
Powell, Jonathan D.
Meyers, David J.
De Marzo, Angelo M.
Berman, David M.
Lotan, Tamara L.
DEVELOPMENTAL BIOLOGY, 2011, 360 (02) : 329 - 342
[47] PI3K/mTOR Signaling Regulates Prostatic Tubulogenesis.
Ghosh, S.
Lau, H.
Simons, B.
Berman, D.
Lotan, T. L.
LABORATORY INVESTIGATION, 2011, 91 : 391A - 391A
[48] Regulation of PTEN translation by PI3K signaling maintains pathway homeostasis
Mukherjee, Radha
Vanaja, Kiran G.
Boyer, Jacob A.
Gadal, Sunyana
Solomon, Hilla
Chandarlapaty, Sarat
Levchenko, Andre
Rosen, Neal
MOLECULAR CELL, 2021, 81 (04) : 708 - +
[49] PI(3,4,5)P3 and PI(3,4)P2 levels correlate with PKB/akt phosphorylation at Thr308 and Ser473, respectively;: PI(3,4)P2 levels determine PKB activity
Ma, Kewei
Cheung, Samuel M.
Marshall, Aaron J.
Duronio, Vincent
CELLULAR SIGNALLING, 2008, 20 (04) : 684 - 694
[50] The Role of PI3kγ and PI3kΔ in Alloimmunity
Uehara, M.
Jamil, A.
Solhjou, Z.
McGrath, M.
Banouni, N.
Evans, C.
Dinitto, J.
Winkler, D.
Abdi, R.
AMERICAN JOURNAL OF TRANSPLANTATION, 2016, 16 : 325 - 325

← 1 2 3 4 5 →