CD22

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Siglec Paradigm 1: CD22

CD22 is predominately expressed on B cells and is well documented as a regulator of B cell receptor (BCR) signaling1. It is one of 4 siglecs that are highly conserved among mammals. This paradigm is unique among the siglecs in that the cytoplasmic domain has 6 conserved tyrosine motifs, including 3 immunoreceptor tyrosine inhibitory motifs (ITIM), one ITIM-like motif, and a growth factor receptor bound protein2 (GRB2) motif. These tyrosine motifs are involved in regulation of BCR signaling and also mediate its constitutive clathrin mediated endocytosis, an activity believed to be tied to its regulation of cell signaling. The preferred glycan ligand of CD22 differs significantly in humans and mice1-3. While both recognize the sequence Siaa-2-6Galb-1-4GlcNAc expressed abundantly on B cells, murine CD22 prefers Neu5Gc (not found in humans) over Neu5Ac, while human CD22 exhibits highest affinity for sulfated sialoside, Neu5Aca-2-6Galb-1-4[6S]GlcNAc, demonstrating significant evolution of ligand specificity with conservation of function. Although CD22 recognizes ligands on the same cell in cis, it also binds to ligands in trans if expressed on adjacent contacting cells. A major area of investigation is to understand the relative roles of cis and trans ligands in CD22 function.

Contents

   * CFG Participating Investigators (PIs) contributing to the understanding of this paradigm
   * CFG resources used in investigations
           - Glycogene microarray
           - Knockout mice
           - Glycan array Progress toward understanding this paradigm
   *
           - Carbohydrate ligands
           - Cellular expression
           - Structure
           - Biological roles of GBP-ligand interactions Related glycan-binding proteins (GBPs)
 * * References 


CFG Participating Investigators (PIs) contributing to the understanding of this paradigm Participating Investigators (PIs) of the CFG have made major contributions to the understanding of the biology of human and murine CD22. These include: Nicolai Bovin, Paul Crocker, Jamey Marth, David Nemazee, Lars Nitschke, Jim Paulson, and Ajit Varki.


CFG resources used in investigations

  1. Glycogene microarray

The CFG glycogene microarray has been used to show that the ligands of CD22 are downregulated upon B cell activation.

  1. Knockout mouse lines

Mice deficient in CD22 and the sialyltransferase responsible for synthesis of its ligands (ST6Gal I) distributed by the CFG have been instrumental in understanding the biology of CD22.

  1. Glycan array

The glycan microarray of the CFG was instrumental in identification of the high affinity ligand of CD22 as a sialylated-sulfated glycan

  1. CFG Resources and Data Resources
  2. Data - All

- Glycan profiling - Glycogene microarray - Knockout mouse phenotyping - Glycan array

  1. Molecule pages - All

- Glycan structures - GBP molecules - Glycosyltransferases Progress toward understanding this paradigm

  1. Carbohydrate ligands
  2. Cellular expression
  3. Structure
  4. Biological roles of GBP-ligand interaction


Related glycan-binding proteins (GBPs)

None. This paradigm is unique among the siglecs in that the cytoplasmic domain has 6 conserved tyrosine motifs, including 3 immunoreceptor tyrosine inhibitory motifs (ITIM), one ITIM-like motif, and a growth factor receptor bound protein2 (GRB2) motif.


References

1. Crocker, P. R., Paulson, J. C. & Varki, A. Siglecs and their roles in the immune system. Nat Rev Immunol 7, 255-266 (2007). 2. Kimura, N. et al. Human B-lymphocytes express alpha2-6-sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/Siglec-2. J Biol Chem 282, 32200-32207 (2007). 3. Blixt, O. et al. Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc Natl Acad Sci U S A 101, 17033-17038 (2004).

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