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ITIM-dependent endocytosis of CD33-related Siglecs : role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2

Walter, R. B. and Raden, B. W. and Zeng, R. and Häusermann, P. and Bernstein, I. D. and Cooper, J. A.. (2008) ITIM-dependent endocytosis of CD33-related Siglecs : role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2. Journal of leukocyte biology, Vol. 83, no. 1. pp. 200-211.

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Official URL: http://edoc.unibas.ch/dok/A6004963

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Abstract

The leukocyte CD33-related sialic acid-binding Ig-like lectins (Siglecs) are implicated in glycan recognition and host defense against and pathogenicity of sialylated pathogens. Recent studies have shown endocytosis by CD33-related Siglecs, which is implicated in clearance of sialylated antigens and antigen presentation and makes targeted immunotherapy possible. Using CD33 as a paradigm, we have now investigated the reasons underlying the comparatively slow rate of endocytosis of these receptors. We show that endocytosis is largely limited and determined by the intracellular domain while the extracellular and transmembrane domains play a minor role. Tyrosine phosphorylation, most likely through Src family kinases, increases uptake of CD33 depending on the integrity of the two cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Simultaneous depletion of the protein tyrosine phosphatases, Src homology-2-containing tyrosine phosphatase 1 (Shp1) and Shp2, which bind to phosphorylated CD33, increases internalization of CD33 slightly in some cell lines, whereas depletion of spleen tyrosine kinase (Syk) has no effect, implying that Shp1 and Shp2 can dephosphorylate the ITIMs or mask binding of the phosphorylated ITIMs to an endocytic adaptor. Our studies show that restraint of CD33 internalization through the intracellular domain is relieved partly when the ITIMs are phosphorylated and show that Shp1 and Shp2 can modulate this process.
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialfächer (Klinik) > Dermatologie USB > Dermatologie und Venerologie (Itin)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialfächer (Klinik) > Dermatologie USB > Dermatologie und Venerologie (Itin)
UniBasel Contributors:Häusermann, Peter
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Society for Leukocyte Biology
ISSN:0741-5400
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 Apr 2014 08:00
Deposited On:25 Apr 2014 08:00

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