The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2

被引：48

作者：

Dyson, JM ^{[1
]}

Kong, AM ^{[1
]}

Wiradjaja, F ^{[1
]}

Astle, MV ^{[1
]}

Gurung, R ^{[1
]}

Mitchell, CA ^{[1
]}

机构：

[1] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2005年 / 37卷 / 11期

关键词：

insulin signaling; phosphoinositide; SHIP2;

D O I：

10.1016/j.biocel.2005.05.003

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：

Phosphoinositides are membrane-bound signaling molecules that recruit, activate and localize target effectors to intracellular membranes regulating apoptosis, cell proliferation, insulin signaling and membrane trafficking. The SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3) generating phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P-2) Overexpression of SHIP2 inhibits insulin-stimulated phosphoinositide 3-kinase (PI3K) dependent signaling events. Analysis of diabetic human subjects has revealed an association between SHIP2 gene polymorphisms and type 2 diabetes mellitus. Genetic ablation of SHIP2 in mice has generated conflicting results. SHIP2 knockout mice were originally reported to show lethal neonatal hypoglycemia resulting from insulin hypersensitivity, but in addition to inactivating the SHIP2 gene, the Phox2a gene was also inadvertently deleted. Another SHIP2 knockout mouse has now been generated which inactivates the SHIP2 gene but leaves Phox2a intact. These animals show normal insulin and glucose tolerance but are highly resistant to weight gain on high fat diets, exhibiting an obesity-resistant phenotype. Therefore, SHIP2 remains a significant therapeutic target for the treatment of both obesity and type 2 diabetes. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2260 / 2265

页数：6

共 22 条

[1] The termination of PI3K signalling by SHIP1 and SHIP2 inositol 5-phosphatases [J].

Backers, K ;

Blero, D ;

Paternotte, N ;

Zhang, J ;

Erneux, C .

ADVANCES IN ENZYME REGULATION, VOL 43, 2003, 43 :15-28

[2] Phox2 genes -: from patterning to connectivity [J].

Brunet, JF ;

Pattyn, A .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2002, 12 (04) :435-440

[3] The phosphoinositide 3-kinase pathway [J].

Cantley, LC .

SCIENCE, 2002, 296 (5573) :1655-1657

[4] Comparative mechanistic and substrate specificity study of inositol polyphosphate 5-phosphatase Schizosaccharomyces pombe synaptojanin and SHIP2 [J].

Chi, YL ;

Zhou, B ;

Wang, WQ ;

Chung, SK ;

Kwon, YU ;

Ahn, YH ;

Chang, YT ;

Tsujishita, Y ;

Hurley, JH ;

Zhang, ZY .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (43) :44987-44995

[5] The lipid phosphatase SHIP2 controls insulin sensitivity (vol 409, pg 92, 2001) [J].

Clément, S ;

Krause, U ;

Desmedt, F ;

Tanti, JF ;

Behrends, J ;

Pesesse, X ;

Sasaki, T ;

Penninger, J ;

Doherty, M ;

Malaisse, W ;

Dumont, JE ;

Le Marchand-Brustel, Y ;

Erneux, C ;

Hue, L ;

Schurmans, S .

NATURE, 2004, 431 (7010) :878-878

[6] The lipid phosphatase SHIP2 controls insulin sensitivity [J].

Clément, S ;

Krause, U ;

Desmedt, F ;

Tanti, JF ;

Behrends, J ;

Pesesse, X ;

Sasaki, T ;

Penninger, J ;

Doherty, M ;

Malaisse, W ;

Dumont, JE ;

Le Marchand-Brustel, Y ;

Erneux, C ;

Hue, L ;

Schurmans, S .

NATURE, 2001, 409 (6816) :92-97

[7] Dynamics of phosphoinositides in membrane retrieval and insertion [J].

Czech, MP .

ANNUAL REVIEW OF PHYSIOLOGY, 2003, 65 :791-815

[8] SHIP-2 and PTEN are expressed and active in vascular smooth muscle cell nuclei, but only SHIP-2 is associated with nuclear speckles [J].

Déléris, P ;

Bacqueville, D ;

Gayral, S ;

Carrez, L ;

Salles, JP ;

Perret, B ;

Breton-Douillon, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (40) :38884-38891

[9] The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2, binds filamin and regulates submembraneous actin [J].

Dyson, JM ;

O'Malley, CJ ;

Becanovic, J ;

Munday, AD ;

Berndt, MC ;

Coghill, ID ;

Nandurkar, HH ;

Ooms, LM ;

Mitchell, CA .

JOURNAL OF CELL BIOLOGY, 2001, 155 (06) :1065-1079

[10] Impact of Src homology 2-containing inositol 5′-phosphatase 2 gene polymorphisms detected in a Japanese population on insulin signaling [J].

Kagawa, S ;

Sasaoka, T ;

Yaguchi, S ;

Ishihara, H ;

Tsuneki, H ;

Murakami, S ;

Fukui, K ;

Wada, T ;

Kobayashi, S ;

Kimura, I ;

Kobayashi, M .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (05) :2911-2919

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