HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by John, B. Articles by Justement, L. B. Search for Related Content PubMed PubMed Citation Articles by John, B. Articles by Justement, L. B.

The B Cell Coreceptor CD22 Associates with AP50, a Clathrin-Coated Pit Adapter Protein, Via Tyrosine-Dependent Interaction¹

BinuJoy John^2,*, Brantley R. Herrin^2,,, Chander Raman, Yan-ni Wang^,, Kevin R. Bobbitt^*, Brian A. Brody^, and Louis B. Justement^3,*,,

^* Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555; and Division of Developmental and Clinical Immunology, Department of Microbiology, and Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, AL 35294

The B cell coreceptor CD22 plays an important role in regulating signal transduction via the B cell Ag receptor. Studies have shown that surface expression of CD22 can be modulated in response to binding of ligand (i.e., mAb). Thus, it is possible that alterations in the level of CD22 expression following binding of natural ligand(s) may affect its ability to modulate the Ag receptor signaling threshold at specific points during B cell development and differentiation. Therefore, it is important to delineate the physiologic mechanism by which CD22 expression is controlled. In the current study, yeast two-hybrid analysis was used to demonstrate that CD22 interacts with AP50, the medium chain subunit of the AP-2 complex, via tyrosine-based internalization motifs in its cytoplasmic domain. This interaction was further characterized using yeast two-hybrid analysis revealing that Tyr⁸⁴³ and surrounding amino acids in the cytoplasmic tail of CD22 comprise the primary binding site for AP50. Subsequent studies using transfectant Jurkat cell lines expressing wild-type or mutant forms of CD22 demonstrated that either Tyr⁸⁴³ or Tyr⁸⁶³ is sufficient for mAb-mediated internalization of CD22 and that these motifs are involved in its interaction with the AP-2 complex, as determined by coprecipitation of -adaptin. Finally, experiments were performed demonstrating that treatment of B cells with either intact anti-Ig Ab or F(ab')₂ blocks ligand-mediated internalization of CD22. In conclusion, these studies demonstrate that internalization of CD22 is dependent on its association with the AP-2 complex via tyrosine-based internalization motifs.

This article has been cited by other articles:

				R. B. Walter, B. W. Raden, R. Zeng, P. Hausermann, I. D. Bernstein, and J. A. Cooper ITIM-dependent endocytosis of CD33-related Siglecs: role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2 J. Leukoc. Biol., January 1, 2008; 83(1): 200 - 211. [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]

				B. E. Collins, O. Blixt, S. Han, B. Duong, H. Li, J. K. Nathan, N. Bovin, and J. C. Paulson High-Affinity Ligand Probes of CD22 Overcome the Threshold Set by cis Ligands to Allow for Binding, Endocytosis, and Killing of B Cells. J. Immunol., September 1, 2006; 177(5): 2994 - 3003. [Abstract] [Full Text] [PDF]

				K. M. Haas, S. Sen, I. G. Sanford, A. S. Miller, J. C. Poe, and T. F. Tedder CD22 Ligand Binding Regulates Normal and Malignant B Lymphocyte Survival In Vivo. J. Immunol., September 1, 2006; 177(5): 3063 - 3073. [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]

				R. B. Walter, B. W. Raden, D. M. Kamikura, J. A. Cooper, and I. D. Bernstein Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity Blood, February 1, 2005; 105(3): 1295 - 1302. [Abstract] [Full Text] [PDF]

				C. Scott, M. E. Higgins, J. P. Davies, and Y. A. Ioannou Targeting of NPC1 to Late Endosomes Involves Multiple Signals, Including One Residing within the Putative Sterol-sensing Domain J. Biol. Chem., November 12, 2004; 279(46): 48214 - 48223. [Abstract] [Full Text] [PDF]

				M. Zhang and A. Varki Cell surface sialic acids do not affect primary CD22 interactions with CD45 and surface IgM nor the rate of constitutive CD22 endocytosis Glycobiology, November 1, 2004; 14(11): 939 - 949. [Abstract] [Full Text] [PDF]

				B. E. Collins, O. Blixt, A. R. DeSieno, N. Bovin, J. D. Marth, and J. C. Paulson Masking of CD22 by cis ligands does not prevent redistribution of CD22 to sites of cell contact PNAS, April 20, 2004; 101(16): 6104 - 6109. [Abstract] [Full Text] [PDF]