| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Cell Biology and Immunology, The Wellcome Trust Biocentre, University of Dundee, Dundee, United Kingdom; and
Centre d’Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Sante et de la Recherche Médicale-Université de la Méditerranée, Marseille, France
Siglec-7 and Siglec-9 are two members of the recently characterized CD33-related Siglec family of sialic acid binding proteins and are both expressed on human monocytes and NK cells. In addition to their ability to recognize sialic acid residues, these Siglecs display two conserved tyrosine-based motifs in their cytoplasmic region similar to those found in inhibitory receptors of the immune system. In the present study, we use the rat basophilic leukemia (RBL) model to examine the potential of Siglecs-7 and -9 to function as inhibitory receptors and investigate the molecular basis for this. We first demonstrate that Siglecs-7 and -9 are able to inhibit the Fc
RI-mediated serotonin release from RBL cells following co-crosslinking. In addition, we show that under these conditions or after pervanadate treatment, Siglecs-7 and -9 associate with the Src homology region 2 domain-containing phosphatases (SHP), SHP-1 and SHP-2, both in immunoprecipitation and in fluorescence microscopy experiments using GFP fusion proteins. We then show by site-directed mutagenesis that the membrane-proximal tyrosine motif is essential for the inhibitory function of both Siglec-7 and -9, and is also required for tyrosine phosphorylation and recruitment of SHP-1 and SHP-2 phosphatases. Finally, mutation of the membrane-proximal motif increased the sialic acid binding activity of Siglecs-7 and -9, raising the possibility that "inside-out" signaling may occur to regulate ligand binding.
This article has been cited by other articles:
|
|
 |
|
  D. J. Song, J. Y. Cho, S. Y. Lee, M. Miller, P. Rosenthal, P. Soroosh, M. Croft, M. Zhang, A. Varki, and D. H. Broide Anti-Siglec-F Antibody Reduces Allergen-Induced Eosinophilic Inflammation and Airway Remodeling J. Immunol., October 15, 2009; 183(8): 5333 - 5341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Carlin, S. Uchiyama, Y.-C. Chang, A. L. Lewis, V. Nizet, and A. Varki Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response Blood, April 2, 2009; 113(14): 3333 - 3336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Gunnarsson, L. Levander, P. Pahlsson, and M. Grenegard The acute-phase protein {alpha}1-acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin-like lectins (Siglecs) FASEB J, December 1, 2007; 21(14): 4059 - 4069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tateno, H. Li, M. J. Schur, N. Bovin, P. R. Crocker, W. W. Wakarchuk, and J. C. Paulson Distinct Endocytic Mechanisms of CD22 (Siglec-2) and Siglec-F Reflect Roles in Cell Signaling and Innate Immunity Mol. Cell. Biol., August 15, 2007; 27(16): 5699 - 5710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zhang, T. Angata, J. Y. Cho, M. Miller, D. H. Broide, and A. Varki Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils Blood, May 15, 2007; 109(10): 4280 - 4287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Carlin, A. L. Lewis, A. Varki, and V. Nizet Group B Streptococcal Capsular Sialic Acids Interact with Siglecs (Immunoglobulin-Like Lectins) on Human Leukocytes J. Bacteriol., February 15, 2007; 189(4): 1231 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Orr, N. M. Morgan, R. J. Buick, C. R. Boyd, J. Elliott, J. F. Burrows, C. A. Jefferies, P. R. Crocker, and J. A. Johnston SOCS3 Targets Siglec 7 for Proteasomal Degradation and Blocks Siglec 7-mediated Responses J. Biol. Chem., February 9, 2007; 282(6): 3418 - 3422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Attrill, A. Imamura, R. S. Sharma, M. Kiso, P. R. Crocker, and D. M. F. van Aalten Siglec-7 Undergoes a Major Conformational Change When Complexed with the {alpha}(2,8)-Disialylganglioside GT1b J. Biol. Chem., October 27, 2006; 281(43): 32774 - 32783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Avril, S. J. North, S. M. Haslam, H. J. Willison, and P. R. Crocker Probing the cis interactions of the inhibitory receptor Siglec-7 with {alpha}2,8-disialylated ligands on natural killer cells and other leukocytes using glycan-specific antibodies and by analysis of {alpha}2,8-sialyltransferase gene expression J. Leukoc. Biol., October 1, 2006; 80(4): 787 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Avril, E. R. Wagner, H. J. Willison, and P. R. Crocker Sialic Acid-Binding Immunoglobulin-Like Lectin 7 Mediates Selective Recognition of Sialylated Glycans Expressed on Campylobacter jejuni Lipooligosaccharides Infect. Immun., July 1, 2006; 74(7): 4133 - 4141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Nguyen, N. Hurtado-Ziola, P. Gagneux, and A. Varki Loss of Siglec expression on T lymphocytes during human evolution PNAS, May 16, 2006; 103(20): 7765 - 7770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, A. Raper, N. Sugita, R. Hingorani, M. Salio, M. J. Palmowski, V. Cerundolo, and P. R. Crocker Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors Blood, May 1, 2006; 107(9): 3600 - 3608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Varki and T. Angata Siglecs--the major subfamily of I-type lectins Glycobiology, January 1, 2006; 16(1): 1R - 27R. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamaji, M. Mitsuki, T. Teranishi, and Y. Hashimoto Characterization of inhibitory signaling motifs of the natural killer cell receptor Siglec-7: attenuated recruitment of phosphatases by the receptor is attributed to two amino acids in the motifs Glycobiology, July 1, 2005; 15(7): 667 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Avril, S. D. Freeman, H. Attrill, R. G. Clarke, and P. R. Crocker Siglec-5 (CD170) Can Mediate Inhibitory Signaling in the Absence of Immunoreceptor Tyrosine-based Inhibitory Motif Phosphorylation J. Biol. Chem., May 20, 2005; 280(20): 19843 - 19851. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
