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Vol. 273, Issue 2, 763-770, January 9, 1998
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From the The selectin family of cell adhesion molecules
mediates the tethering and rolling of leukocytes on blood vessel
endothelium. It has been postulated that the molecular basis of this
highly dynamic adhesion is the low affinity and rapid kinetics of
selectin interactions. However, affinity and kinetic analyses of
monomeric selectins binding their natural ligands have not previously
been reported. Leukocyte selectin (L-selectin, CD62L) binds
preferentially to O-linked carbohydrates present on a small
number of mucin-like glycoproteins, such as
glycosylation-dependent cell adhesion molecule-1 (GlyCAM-1), expressed in high endothelial venules. GlyCAM-1 is a
soluble secreted protein which, following binding to CD62L, stimulates
Medical Research Council Cellular Immunology
Unit, Sir William Dunn School of Pathology, University of Oxford,
Oxford OX1 3RE, United Kingdom and the § Department of
Anatomy and Program in Immunology, University of California,
San Francisco, California 94143-0452
2-integrin-mediated adhesion of lymphocytes. Using surface plasmon resonance, we show that a soluble monomeric form of
CD62L binds to purified immobilized GlyCAM-1 with a dissociation constant (Kd) of 108 µM. CD62L
dissociates from GlyCAM-1 with a very fast dissociation rate constant
(
10 s
1) which agrees well with the reported
dissociation rate constant of CD62L-mediated leukocyte tethers. The
calculated association rate constant is 105
M1 s1. At concentrations just
above its mean serum level (~1.5 µg/ml or ~30 nM),
GlyCAM-1 binds multivalently to immobilized CD62L. It follows that
soluble GlyCAM-1 may cross-link CD62L when it binds to cells,
suggesting a mechanism for signal transduction.
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A. Bistrup, S. Bhakta, J. K. Lee, Y. Y. Belov, M. D. Gunn, F.-R. Zuo, C.-C. Huang, R. Kannagi, S. D. Rosen, and S. Hemmerich Sulfotransferases of Two Specificities Function in the Reconstitution of High Endothelial Cell Ligands for L-selectin J. Cell Biol., May 17, 1999; 145(4): 899 - 910. [Abstract] [Full Text] [PDF]
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S. Chen and T. A. Springer An Automatic Braking System That Stabilizes Leukocyte Rolling by an Increase in Selectin Bond Number with Shear J. Cell Biol., January 11, 1999; 144(1): 185 - 200. [Abstract] [Full Text] [PDF]
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Y. Tominaga, Y. Kita, A. Satoh, S. Asai, K. Kato, K. Ishikawa, T. Horiuchi, and T. Takashi Affinity and Kinetic Analysis of the Molecular Interaction of ICAM-1 and Leukocyte Function-Associated Antigen-1 J. Immunol., October 15, 1998; 161(8): 4016 - 4022. [Abstract] [Full Text] [PDF]
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 X. Li, D. A. Steeber, M. L.K. Tang, M. A. Farrar, R. M. Perlmutter, and T. F. Tedder Regulation of L-Selectin-mediated Rolling through Receptor Dimerization J. Exp. Med., October 5, 1998; 188(7): 1385 - 1390. [Abstract] [Full Text] [PDF]
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R. Alon, S. Chen, R. Fuhlbrigge, K. D. Puri, and T. A. Springer The kinetics and shear threshold of transient and rolling interactions of L-selectin with its ligand on leukocytes PNAS, September 29, 1998; 95(20): 11631 - 11636. [Abstract] [Full Text] [PDF]
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K. R. Snapp, R. Craig, M. Herron, R. D. Nelson, L. M. Stoolman, and G. S. Kansas Dimerization of P-Selectin Glycoprotein Ligand-1 (PSGL-1) Required for Optimal Recognition of P-Selectin J. Cell Biol., July 13, 1998; 142(1): 263 - 270. [Abstract] [Full Text] [PDF]
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S. J. Davis, E. A. Davies, M. G. Tucknott, E. Y. Jones, and P. A. van der Merwe The role of charged residues mediating low affinity protein-protein recognition at the cell surface by CD2 PNAS, May 12, 1998; 95(10): 5490 - 5494. [Abstract] [Full Text] [PDF]
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N. J. MacDonald, W. Y. Shivers, D. L. Narum, S. M. Plum, J. N. Wingard, S. R. Fuhrmann, H. Liang, J. Holland-Linn, D. H. T. Chen, and B. K. L. Sim Endostatin Binds Tropomyosin. A POTENTIAL MODULATOR OF THE ANTITUMOR ACTIVITY OF ENDOSTATIN J. Biol. Chem., June 29, 2001; 276(27): 25190 - 25196. [Abstract] [Full Text] [PDF]
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M. K. Wild, M.-C. Huang, U. Schulze-Horsel, P. A. van der Merwe, and D. Vestweber Affinity, Kinetics, and Thermodynamics of E-selectin Binding to E-selectin Ligand-1 J. Biol. Chem., August 17, 2001; 276(34): 31602 - 31612. [Abstract] [Full Text] [PDF]
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K. Maenaka, P. A. van der Merwe, D. I. Stuart, E. Y. Jones, and P. Sondermann The Human Low Affinity Fcgamma Receptors IIa, IIb, and III Bind IgG with Fast Kinetics and Distinct Thermodynamic Properties J. Biol. Chem., November 21, 2001; 276(48): 44898 - 44904. [Abstract] [Full Text] [PDF]
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V. Ramachandran, T. Yago, T. K. Epperson, M. M. A. Kobzdej, M. U. Nollert, R. D. Cummings, C. Zhu, and R. P. McEver From the Cover: Dimerization of a selectin and its ligand stabilizes cell rolling and enhances tether strength in shear flow PNAS, August 28, 2001; 98(18): 10166 - 10171. [Abstract] [Full Text] [PDF]
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