|
|
Blood, 15 January 2006, Vol. 107, No. 2, pp. 813-820.
Prepublished online as a Blood First Edition Paper on September 22, 2005; DOI 10.1182/blood-2005-05-1841.
 Previous Article | Next Article 
Submitted May 6, 2005
Accepted September 9, 2005
The inositol phosphatase SHIP-2 downregulates Fc R-mediated phagocytosis in murine macrophages independently of SHIP-1
Jing Ai, Amita Maturu, Wesley Johnson, Yijie Wang, Clay B Marsh, and Susheela Tridandapani*
The Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH, USA
Department of Internal Medicine, Dorothy M. Davis Heart and Lung Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
* Corresponding author; email: tridandapani.2{at}osu.edu.
Fc R-mediated phagocytosis of IgG-coated particles is a complex process involving the activation of multiple signaling enzymes, and is regulated by the inositol phosphatases PTEN and SHIP-1. In a recent study we have demonstrated that SHIP-2, an inositol phosphatase with high level homology to SHIP-1, is involved in FcR signaling. However, it is not known whether SHIP-2 plays a role in modulating phagocytosis. In this study we have analyzed the role of SHIP-2 in FcR-mediated phagocytosis using independent cell models that allow for manipulation of SHIP-2 function without influencing the highly homologous SHIP-1. We present evidence that SHIP-2 translocates to the site of phagocytosis and downregulates FcR-mediated phagocytosis. Our data indicate that SHIP-2 must contain both the N-terminal SH2 domain and the C-terminal proline-rich domain to mediate its inhibitory effect. The effect of SHIP-2 is independent of SHIP-1, as overexpression of dominant-negative SHIP-2 in SHIP-1 deficient primary macrophages resulted in enhanced phagocytic efficiency. Likewise, specific knockdown of SHIP-2 expression using siRNA resulted in enhanced phagocytosis. Finally, analysis of the molecular mechanism of SHIP-2 downregulation of phagocytosis revealed that SHIP-2 downregulates upstream activation of Rac. Thus, we conclude that SHIP-2 is a novel negative regulator of FcR-mediated phagocytosis independent of SHIP-1.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. A. Kamen, J. Levinsohn, A. Cadwallader, S. Tridandapani, and J. A. Swanson
SHIP-1 Increases Early Oxidative Burst and Regulates Phagosome Maturation in Macrophages
J. Immunol.,
June 1, 2008;
180(11):
7497 - 7505.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. Horan, K.-i. Watanabe, A. M. Kong, C. G. Bailey, J. E. J. Rasko, T. Sasaki, and C. A. Mitchell
Regulation of Fc{gamma}R-stimulated phagocytosis by the 72-kDa inositol polyphosphate 5-phosphatase: SHIP1, but not the 72-kDa 5-phosphatase, regulates complement receptor 3 mediated phagocytosis by differential recruitment of these 5-phosphatases to the phagocytic cup
Blood,
December 15, 2007;
110(13):
4480 - 4491.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-H. Leung and S. Bolland
The Inositol 5'-Phosphatase SHIP-2 Negatively Regulates IgE-Induced Mast Cell Degranulation and Cytokine Production
J. Immunol.,
July 1, 2007;
179(1):
95 - 102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Kamen, J. Levinsohn, and J. A. Swanson
Differential Association of Phosphatidylinositol 3-Kinase, SHIP-1, and PTEN with Forming Phagosomes
Mol. Biol. Cell,
July 1, 2007;
18(7):
2463 - 2472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
