Tumor Suppression by Phospholipase C-β3 via SHP-1-Mediated Dephosphorylation of Stat5

被引：63

作者：

Xiao, Wenbin ^{[1
]}

Hong, Hong ^{[1
]}

Kawakami, Yuko ^{[1
]}

Kato, Yuko ^{[2
]}

Wu, Dianqing ^{[3
,4
]}

Yasudo, Hiroki ^{[1
]}

Kimura, Akiko ^{[5
]}

Kubagawa, Hiromi ^{[6
]}

Bertoli, Luigi F. ^{[8
]}

Davis, Randall S. ^{[7
]}

Chau, Luan A. ^{[9
]}

Madrenas, Joaquin ^{[9
]}

Hsia, Cyrus C. ^{[10
]}

Xenocostas, Anargyros ^{[10
]}

Kipps, Thomas J. ^{[11
]}

Hennighausen, Lothar ^{[5
]}

Iwama, Atsushi ^{[2
]}

Nakauchi, Hiromitsu ^{[12
]}

Kawakami, Toshiaki ^{[1
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

[2] Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chiba 2608670, Japan

[3] Yale Univ, Sch Med, Program Vasc Biol & Therapeut, New Haven, CT 06520 USA

[4] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

[5] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA

[6] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA

[7] Univ Alabama, Dept Med, Birmingham, AL 35294 USA

[8] Brookwood Med Ctr, Birmingham, AL 35209 USA

[9] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5K8, Canada

[10] Univ Western Ontario, Dept Med, London, ON N6A 4G5, Canada

[11] Univ Calif San Diego, Dept Internal Med, La Jolla, CA 92093 USA

[12] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Lab Stem Cell Therapy, Tokyo 1088639, Japan

来源：

CANCER CELL | 2009年 / 16卷 / 02期

基金：

美国国家卫生研究院;

关键词：

TYROSINE-PHOSPHATASE SHP-1; COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; CHRONIC MYELOID-LEUKEMIA; BETA-GAMMA-SUBUNITS; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; JAK-STAT5; PATHWAY; SIGNAL TRANSDUCER; SELF-RENEWAL;

D O I：

10.1016/j.ccr.2009.05.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Given its catalytic activity to generate diacylglycerol and inositol 1,4,5-trisphosphate, phospholipase C (PLC) is implicated in promoting cell growth. However, we found that PLC-beta 3-deficient mice develop myeloproliferative disease, lymphoma, and other tumors. The mutant mice have increased numbers of hematopoietic stem cells with increased proliferative, survival, and myeloid-differentiative abilities. These properties are dependent on Stat5 and can be antagonized by the protein phosphatase SHP-1. Stat5-dependent cooperative transformation by activec-Myc and PLC-beta 3 deficiency was suggested in mouse lymphomas in PLC-beta 3(-/-) and in E mu-myc;PLC-beta 3(+/-) mice and human Burkitt's lymphoma cells. The same mechanism for malignant transformation seems to be operative in other human lymphoid and myeloid malignancies. Thus, PLC-beta 3 is likely a tumor suppressor.

引用

页码：161 / 171

页数：11

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