| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print January 5, 2004
J. Biol. Chem, 10.1074/jbc.M311633200
Submitted on October 23, 2003
Revised on January 5, 2004
Accepted on January 5, 2004
Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226
Corresponding Author: bvolkman{at}mcw.edu
Chemokine-mediated recruitment of leukocytes in vivo depends on interactions with cell-surface glycosaminoglycans. Lymphotactin, the unique member of the ‘C’ chemokine subclass, is a highly basic protein that binds heparin, a glycosaminoglycan, with high affinity (~10 nM). We detected lymphotactin-heparin binding by NMR and mapped this interaction to a narrow surface that wraps around the protein. Substitutions in and around this binding site and surface plasmon resonance analysis of heparin binding affinity identified two arginine residues of lymphotactin as critical for glycosaminoglycan binding. Both arginine mutant proteins and the combined double mutant had dramatically diminished in vivo activity in a leukocyte recruitment assay, suggesting that the lymphotactin-glycosaminoglycan interactions detected in vitro are important for the function of this chemokine. Our results demonstrate that like other chemokines, lymphotactin utilizes highly specific glycosaminoglycan-binding sites that represent potential targets for drug development.
This article has been cited by other articles:
|
|
 |
|
  R. L. Tuinstra, F. C. Peterson, S. Kutlesa, E. S. Elgin, M. A. Kron, and B. F. Volkman Interconversion between two unrelated protein folds in the lymphotactin native state PNAS, April 1, 2008; 105(13): 5057 - 5062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Alexander-Brett and D. H. Fremont Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor J. Exp. Med., December 24, 2007; 204(13): 3157 - 3172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Zanone, E. Favaro, E. Ferioli, G. C. Huang, N. J. Klein, P. C. Perin, M. Peakman, P. G. Conaldi, and G. Camussi Human pancreatic islet endothelial cells express coxsackievirus and adenovirus receptor and are activated by coxsackie B virus infection FASEB J, October 1, 2007; 21(12): 3308 - 3317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Luttichau, A. H. Johnsen, J. Jurlander, M. M. Rosenkilde, and T. W. Schwartz Kaposi Sarcoma-associated Herpes Virus Targets the Lymphotactin Receptor with Both a Broad Spectrum Antagonist vCCL2 and a Highly Selective and Potent Agonist vCCL3 J. Biol. Chem., June 15, 2007; 282(24): 17794 - 17805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ali, H. Robertson, J. H. Wain, J. D. Isaacs, G. Malik, and J. A. Kirby A Non-Glycosaminoglycan-Binding Variant of CC Chemokine Ligand 7 (Monocyte Chemoattractant Protein-3) Antagonizes Chemokine-Mediated Inflammation J. Immunol., July 15, 2005; 175(2): 1257 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Veldkamp, F. C. Peterson, A. J. Pelzek, and B. F. Volkman The monomer-dimer equilibrium of stromal cell-derived factor-1 (CXCL 12) is altered by pH, phosphate, sulfate, and heparin Protein Sci., April 1, 2005; 14(4): 1071 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Smith, P. A. Johanesen, M. K. Wendt, D. G. Binion, and M. B. Dwinell CXCL12 activation of CXCR4 regulates mucosal host defense through stimulation of epithelial cell migration and promotion of intestinal barrier integrity Am J Physiol Gastrointest Liver Physiol, February 1, 2005; 288(2): G316 - G326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Munoz and R. J. Linhardt Heparin-Binding Domains in Vascular Biology Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1549 - 1557. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
