Galectin-9

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Galectin-9 is the best-studied of the tandem-repeat galectins and the crystal structure of the N-terminal carbohydrate recognition domain (CRD) is known. In addition, Galectin-9...
Galectin-9 is the best-studied of the tandem-repeat galectins and the crystal structure of the N-terminal carbohydrate recognition domain (CRD) is known. In addition, Galectin-9...
* uniquely binds poly-N-acetyllactosamine sequences by recognizing internal N-acetyllactosamine repeats<ref>Nagae, M. et al. Structural analysis of the recognition mechanism of poly-N-acetyllactosamine by the human galectin-9 N-terminal carbohydrate recognition domain. Glycobiology 19, 112-117 (2009). </ref>
* uniquely binds poly-N-acetyllactosamine sequences by recognizing internal N-acetyllactosamine repeats<ref>Nagae, M. et al. Structural analysis of the recognition mechanism of poly-N-acetyllactosamine by the human galectin-9 N-terminal carbohydrate recognition domain. Glycobiology 19, 112-117 (2009). </ref>
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* binds distinct ligands from [[Galectin-1]]<ref>Bi, S., Earl, L.A., Jacobs, L. & Baum, L.G. Structural features of galectin-9 and galectin-1 that determine distinct T cell death pathways. J Biol Chem 283, 12248-12258 (2008).</ref>
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* binds distinct ligands from [[Galectin-1]]<ref name="Bi 2008">Bi, S., Earl, L.A., Jacobs, L. & Baum, L.G. Structural features of galectin-9 and galectin-1 that determine distinct T cell death pathways. J Biol Chem 283, 12248-12258 (2008).</ref>
* has three well-characterized linker domains between the CRDs, generated by alternative splicing, that regulate cellular localization and function of the protein
* has three well-characterized linker domains between the CRDs, generated by alternative splicing, that regulate cellular localization and function of the protein
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* is the only tandem-repeat galectin that has been administered in animal models of disease to assess therapeutic potential<ref>Baba, M. et al. Galectin-9 inhibits glomerular hypertrophy in db/db diabetic mice via cell-cycle-dependent mechanisms. J Am Soc Nephrol 16, 3222-3234 (2005). </ref><ref name="Seki 2008">Seki, M. et al. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis. Clin Immunol 127, 78-88 (2008).
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* is the only tandem-repeat galectin that has been administered in animal models of disease to assess therapeutic potential<ref>Baba, M. et al. Galectin-9 inhibits glomerular hypertrophy in db/db diabetic mice via cell-cycle-dependent mechanisms. J Am Soc Nephrol 16, 3222-3234 (2005). </ref><ref name="Seki 2008">Seki, M. et al. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis. Clin Immunol 127, 78-88 (2008).</ref><ref name="Tsuchiyama 2000">Tsuchiyama, Y. et al. Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats. Kidney Int 58, 1941-1952 (2000). </ref>
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</ref><ref>Tsuchiyama, Y. et al. Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats. Kidney Int 58, 1941-1952 (2000). </ref>
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* null mice have increased susceptibility to autoimmune disease
* null mice have increased susceptibility to autoimmune disease
* binds to a unique glycoprotein ligand Tim-3 expressed in Th1 and Th17 cells<ref name="Seki 2008" /><ref>Naka, E.L., Ponciano, V.C., Cenedeze, M.A., Pacheco-Silva, A. & Camara, N.O. Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode. Int Immunopharmacol 9, 658-662 (2009).
* binds to a unique glycoprotein ligand Tim-3 expressed in Th1 and Th17 cells<ref name="Seki 2008" /><ref>Naka, E.L., Ponciano, V.C., Cenedeze, M.A., Pacheco-Silva, A. & Camara, N.O. Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode. Int Immunopharmacol 9, 658-662 (2009).
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=== Glycogene microarray ===
=== Glycogene microarray ===
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Probes for human galectin-9 have been included in all versions of the CFG glycogene chip, and probes for mouse galectin-9 are included on versions 2, 3, and 4.  
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Probes for human galectin-9 have been included in all versions of the CFG glycogene chip, and probes for mouse galectin-9 are included on versions 2, 3, and 4.
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Revision as of 23:43, 21 January 2012

Galectin-9 is the best-studied of the tandem-repeat galectins and the crystal structure of the N-terminal carbohydrate recognition domain (CRD) is known. In addition, Galectin-9...

  • uniquely binds poly-N-acetyllactosamine sequences by recognizing internal N-acetyllactosamine repeats[1]
  • binds distinct ligands from Galectin-1[2]
  • has three well-characterized linker domains between the CRDs, generated by alternative splicing, that regulate cellular localization and function of the protein
  • is the only tandem-repeat galectin that has been administered in animal models of disease to assess therapeutic potential[3][4][5]
  • null mice have increased susceptibility to autoimmune disease
  • binds to a unique glycoprotein ligand Tim-3 expressed in Th1 and Th17 cells[4][6][7][8]

Contents

CFG Participating Investigators contributing to the understanding of this paradigm

CFG Participating Investigators (PIs) contributing to the understanding of Galectin-9 include: Linda Baum, Richard Cummings, Gabriel Rabinovich, Sachiko Sato

Progress toward understanding this GBP paradigm

This section documents what is currently known about Galectin-9, its carbohydrate ligand(s), and how they interact to mediate cell communication. Further information can be found in the GBP Molecule Page for human and mouse Galectin-9 in the CFG database.

Carbohydrate ligands


Cellular expression of GBP and ligands


Biosynthesis of ligands


Structure


Biological roles of GBP-ligand interaction


CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for Galectin-9.

Glycan profiling


Glycogene microarray

Probes for human galectin-9 have been included in all versions of the CFG glycogene chip, and probes for mouse galectin-9 are included on versions 2, 3, and 4.

Knockout mouse lines

CFG-generated Galectin-9 knockout mice have been used to study the biological functions of this paradigm GBP. (CFG PI data)

Glycan array

Investigators have used CFG carbohydrate compounds and glycan array screening to study ligand binding specificity of Galectin-9 (for example, click here). To see all glycan array results for Galectin-9, click here.

Related GBPs

Galectin-4 (CFG data), galectin-6, galectin-8 (CFG data), and galectin-12 (CFG data).

References

  1. Nagae, M. et al. Structural analysis of the recognition mechanism of poly-N-acetyllactosamine by the human galectin-9 N-terminal carbohydrate recognition domain. Glycobiology 19, 112-117 (2009).
  2. Bi, S., Earl, L.A., Jacobs, L. & Baum, L.G. Structural features of galectin-9 and galectin-1 that determine distinct T cell death pathways. J Biol Chem 283, 12248-12258 (2008).
  3. Baba, M. et al. Galectin-9 inhibits glomerular hypertrophy in db/db diabetic mice via cell-cycle-dependent mechanisms. J Am Soc Nephrol 16, 3222-3234 (2005).
  4. 4.0 4.1 Seki, M. et al. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis. Clin Immunol 127, 78-88 (2008).
  5. Tsuchiyama, Y. et al. Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats. Kidney Int 58, 1941-1952 (2000).
  6. Naka, E.L., Ponciano, V.C., Cenedeze, M.A., Pacheco-Silva, A. & Camara, N.O. Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode. Int Immunopharmacol 9, 658-662 (2009).
  7. Niwa, H. et al. Stable form of galectin-9, a Tim-3 ligand, inhibits contact hypersensitivity and psoriatic reactions: a potent therapeutic tool for Th1- and/or Th17-mediated skin inflammation. Clin Immunol 132, 184-194 (2009).
  8. Anderson, D.E. TIM-3 as a therapeutic target in human inflammatory diseases. Expert Opin Ther Targets 11, 1005-1009 (2007).

Acknowledgements

The CFG is grateful to the following PIs for their contributions to this wiki page: Linda Baum, Richard Cummings

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