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

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