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

[31] PI3K/AKT Signaling Regulates H3K4 Methylation in Breast Cancer
Spangle, Jennifer M.
Dreijerink, Koen M.
Groner, Anna C.
Cheng, Hailing
Ohlson, Carolynn E.
Reyes, Jaime
Lin, Charles Y.
Bradner, James
Zhao, Jean J.
Roberts, Thomas M.
Brown, Myles
CELL REPORTS, 2016, 15 (12): : 2692 - 2704
[32] p85 plays a critical role in controlling flux through the PI3K/PTEN signaling axis through dual regulation of both p110 (PI3K) and PTEN
Anderson, Deborah H.
CELL CYCLE, 2010, 9 (11) : 2055 - 2056
[33] The PI(3,5)P2 and PI(4,5)P2 Interactomes
Cadmel, Bruno
Schleber, Christine
Condron, Melanie
Patsiouras, Heather
Connolly, Lisa
Catimel, Jenny
Nice, Edouard C.
Burgess, Antony W.
Holmes, Andrew B.
JOURNAL OF PROTEOME RESEARCH, 2008, 7 (12) : 5295 - 5313
[34] PI3Kbeta Regulates Beta-1 Integrin Signaling in Invadopodia Through Formation of P1(3,4)P2
Erami, Z.
Bresnick, A. R.
Backer, J. M.
MOLECULAR BIOLOGY OF THE CELL, 2018, 29 (26) : 226 - 226
[35] miR-363-3p is activated by MYB and regulates osteoporosis pathogenesis via PTEN/PI3K/AKT signaling pathway
Li, Mingyi
Luo, Ruolan
Yang, Wenjian
Zhou, Zhen
Li, Chenxia
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 2019, 55 (05) : 376 - 386
[36] Class I PI3K Is Required for HSC Differentiation
Ames, Kristina
Kaur, Imit
Tong, Meng
Hemmati, Shayda
Tein, Ellen
Glushakow-Smith, Shira
Gurska, Lindsay
Gritsman, Kira
BLOOD, 2019, 134
[37] miR-363-3p is activated by MYB and regulates osteoporosis pathogenesis via PTEN/PI3K/AKT signaling pathway
Mingyi Li
Ruolan Luo
Wenjian Yang
Zhen Zhou
Chenxia Li
In Vitro Cellular & Developmental Biology - Animal, 2019, 55 : 376 - 386
[38] Advances in subunits of PI3K class I in cancer
Cui, Wenli
Cai, Ying
Zhou, Xiaoyan
PATHOLOGY, 2014, 46 (03) : 169 - 176
[39] Quinalozinones as Inhibitors of Class I PI3K Kinases
Rosse, Gerard
ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (01): : 15 - 16
[40] Class I PI3K in oncogenic cellular transformation
L Zhao
P K Vogt
Oncogene, 2008, 27 : 5486 - 5496

← 1 2 3 4 5 →