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Physiol. Rev. 79: 181-213, 1999;
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PHYSIOLOGICAL REVIEWS   Vol. 79 No. 1 January 1999, pp. 181-213
Copyright ©1999 The American Physiological Society

Mechanisms That Regulate the Function of the Selectins and Their Ligands

DIETMAR VESTWEBER AND JAMES E. BLANKS

Institute of Cell Biology, Center of Molecular Biology of Inflammation, University of Münster, Münster, Germany

Vestweber, Dietmar, and James E. Blanks. Mechanisms That Regulate the Function of the Selectins and Their Ligands. Physiol. Rev. 79: 181-213, 1999. --- Selectins are a family of three cell adhesion molecules (L-, E-, and P-selectin) specialized in capturing leukocytes from the bloodstream to the blood vessel wall. This initial cell contact is followed by the selectin-mediated rolling of leukocytes on the endothelial cell surface. This represents the first step in a cascade of molecular interactions that lead to leukocyte extravasation, enabling the processes of lymphocyte recirculation and leukocyte migration into inflamed tissue. The central importance of the selectins in these processes has been well documented in vivo by the use of adhesion-blocking antibodies as well as by studies on selectin gene-deficient mice. This review focuses on the molecular mechanisms that regulate expression and function(s) of the selectins and their ligands. Cell-surface expression of the selectins is regulated by a variety of different mechanisms. The selectins bind to carbohydrate structures on glycoproteins, glycolipids, and proteoglycans. Glycoproteins are the most likely candidates for physiologically relevant ligands. Only a few glycoproteins are appropriately glycosylated to allow strong binding to the selectins. Recently, more knowledge about the structure and the regulated expression of some of the carbohydrates on these ligands necessary for selectin binding has been accumulated. For at least one of these ligands, the physiological function is now well established. A novel and exciting aspect is the signaling function of the selectins and their ligands. Especially in the last two years, convincing data have been published supporting the idea that selectins and glycoprotein ligands of the selectins participate in the activation of leukocyte integrins.




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V. Ramachandran, M. Williams, T. Yago, D. W. Schmidtke, and R. P. McEver
Dynamic alterations of membrane tethers stabilize leukocyte rolling on P-selectin
PNAS, September 14, 2004; 101(37): 13519 - 13524.
[Abstract] [Full Text] [PDF]

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 JCBHome page
T. Yago, J. Wu, C. D. Wey, A. G. Klopocki, C. Zhu, and R. P. McEver
Catch bonds govern adhesion through L-selectin at threshold shear
J. Cell Biol., September 13, 2004; 166(6): 913 - 923.
[Abstract] [Full Text] [PDF]

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 Int ImmunolHome page
H. Kanda, T. Tanaka, M. Matsumoto, E. Umemoto, Y. Ebisuno, M. Kinoshita, M. Noda, R. Kannagi, T. Hirata, T. Murai, et al.
Endomucin, a sialomucin expressed in high endothelial venules, supports L-selectin-mediated rolling
Int. Immunol., September 1, 2004; 16(9): 1265 - 1274.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
W. F. Hanna, C. L. Kerr, J. H. Shaper, and W. W. Wright
Lewis X-Containing Neoglycoproteins Mimic the Intrinsic Ability of Zona Pellucida Glycoprotein ZP3 to Induce the Acrosome Reaction in Capacitated Mouse Sperm
Biol Reprod, September 1, 2004; 71(3): 778 - 789.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. Kilian, J. Dernedde, E.-C. Mueller, I. Bahr, and R. Tauber
The Interaction of Protein Kinase C Isozymes {alpha}, {iota}, and {theta} with the Cytoplasmic Domain of L-selectin Is Modulated by Phosphorylation of the Receptor
J. Biol. Chem., August 13, 2004; 279(33): 34472 - 34480.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Wei, G. Tai, Y. Gao, N. Li, B. Huang, Y. Zhou, S. Hao, and X. Zeng
Modified Heparin Inhibits P-selectin-mediated Cell Adhesion of Human Colon Carcinoma Cells to Immobilized Platelets under Dynamic Flow Conditions
J. Biol. Chem., July 9, 2004; 279(28): 29202 - 29210.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
E. M. Rijcken, M. G. Laukoetter, C. Anthoni, S. Meier, R. Mennigen, H.-U. Spiegel, M. Bruewer, N. Senninger, D. Vestweber, and C. F. Krieglstein
Immunoblockade of PSGL-1 attenuates established experimental murine colitis by reduction of leukocyte rolling
Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G115 - G124.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
S. Szanto, I. Gal, A. Gonda, T. T. Glant, and K. Mikecz
Expression of L-Selectin, but Not CD44, Is Required for Early Neutrophil Extravasation in Antigen-Induced Arthritis
J. Immunol., June 1, 2004; 172(11): 6723 - 6734.
[Abstract] [Full Text] [PDF]

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 BloodHome page
U. Fiedler, M. Scharpfenecker, S. Koidl, A. Hegen, V. Grunow, J. M. Schmidt, W. Kriz, G. Thurston, and H. G. Augustin
The Tie-2 ligand Angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies
Blood, June 1, 2004; 103(11): 4150 - 4156.
[Abstract] [Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
J. D. van Buul and P. L. Hordijk
Signaling in Leukocyte Transendothelial Migration
Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 824 - 833.
[Abstract] [Full Text]

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 Cancer Res.Home page
R. J. Ludwig, B. Boehme, M. Podda, R. Henschler, E. Jager, C. Tandi, W.-H. Boehncke, T. M. Zollner, R. Kaufmann, and J. Gille
Endothelial P-Selectin as a Target of Heparin Action in Experimental Melanoma Lung Metastasis
Cancer Res., April 15, 2004; 64(8): 2743 - 2750.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
H. Xu, A. Manivannan, H.-R. Jiang, J. Liversidge, P. F. Sharp, J. V. Forrester, and I. J. Crane
Recruitment of IFN-{gamma}-Producing (Th1-Like) Cells into the Inflamed Retina In Vivo Is Preferentially Regulated by P-Selectin Glycoprotein Ligand 1:P/E-Selectin Interactions
J. Immunol., March 1, 2004; 172(5): 3215 - 3224.
[Abstract] [Full Text] [PDF]

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 GlycobiologyHome page
L. Nimrichter, A. Gargir, M. Gortler, R. T. Altstock, A. Shtevi, O. Weisshaus, E. Fire, N. Dotan, and R. L. Schnaar
Intact cell adhesion to glycan microarrays
Glycobiology, February 1, 2004; 14(2): 197 - 203.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
E. Hagi-Pavli, P. M. Farthing, and S. Kapas
Stimulation of adhesion molecule expression in human endothelial cells (HUVEC) by adrenomedullin and corticotrophin
Am J Physiol Cell Physiol, February 1, 2004; 286(2): C239 - C246.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
D. Taverna, H. Moher, D. Crowley, L. Borsig, A. Varki, and R. O. Hynes
Increased primary tumor growth in mice null for {beta}3- or {beta}3/{beta}5-integrins or selectins
PNAS, January 20, 2004; 101(3): 763 - 768.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. K. Sarangapani, T. Yago, A. G. Klopocki, M. B. Lawrence, C. B. Fieger, S. D. Rosen, R. P. McEver, and C. Zhu
Low Force Decelerates L-selectin Dissociation from P-selectin Glycoprotein Ligand-1 and Endoglycan
J. Biol. Chem., January 16, 2004; 279(3): 2291 - 2298.
[Abstract] [Full Text] [PDF]

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 JCBHome page
A. Cambi, F. de Lange, N. M. van Maarseveen, M. Nijhuis, B. Joosten, E. M.H.P. van Dijk, B. I. de Bakker, J. A.M. Fransen, P. H.M. Bovee-Geurts, F. N. van Leeuwen, et al.
Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells
J. Cell Biol., January 5, 2004; 164(1): 145 - 155.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y. Hong and P. Stanley
Lec3 Chinese Hamster Ovary Mutants Lack UDP-N-acetylglucosamine 2-Epimerase Activity Because of Mutations in the Epimerase Domain of the Gne Gene
J. Biol. Chem., December 26, 2003; 278(52): 53045 - 53054.
[Abstract] [Full Text] [PDF]

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 JCBHome page
H. Setiadi and R. P. McEver
Signal-dependent distribution of cell surface P-selectin in clathrin-coated pits affects leukocyte rolling under flow
J. Cell Biol., December 22, 2003; 163(6): 1385 - 1395.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
R. Takahashi, Y. Mizukawa, Y. Yamazaki, K. Hayakawa, J. Hayakawa, A. Kudo, and T. Shiohara
In Vitro Differentiation from Naive to Mature E-Selectin Binding CD4 T Cells: Acquisition of Skin-Homing Properties Occurs Independently of Cutaneous Lymphocyte Antigen Expression
J. Immunol., December 1, 2003; 171(11): 5769 - 5777.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
T.-Y. Yen, B. A. Macher, S. Bryson, X. Chang, I. Tvaroska, R. Tse, S. Takeshita, A. M. Lew, and A. Datti
Highly Conserved Cysteines of Mouse Core 2 {beta}1,6-N-Acetylglucosaminyltransferase I Form a Network of Disulfide Bonds and Include a Thiol That Affects Enzyme Activity
J. Biol. Chem., November 14, 2003; 278(46): 45864 - 45881.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
C. Zaph and P. Scott
Th1 Cell-Mediated Resistance to Cutaneous Infection with Leishmania major Is Independent of P- and E-Selectins
J. Immunol., November 1, 2003; 171(9): 4726 - 4732.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
S. Cai and A. E. Davis III
Complement Regulatory Protein C1 Inhibitor Binds to Selectins and Interferes with Endothelial-Leukocyte Adhesion
J. Immunol., November 1, 2003; 171(9): 4786 - 4791.
[Abstract] [Full Text] [PDF]

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 Int ImmunolHome page
M. Kashiwazaki, T. Tanaka, H. Kanda, Y. Ebisuno, D. Izawa, N. Fukuma, N. Akimitsu, K. Sekimizu, M. Monden, and M. Miyasaka
A high endothelial venule-expressing promiscuous chemokine receptor DARC can bind inflammatory, but not lymphoid, chemokines and is dispensable for lymphocyte homing under physiological conditions
Int. Immunol., October 1, 2003; 15(10): 1219 - 1227.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
T. Yago, A. Leppanen, J. A. Carlyon, M. Akkoyunlu, S. Karmakar, E. Fikrig, R. D. Cummings, and R. P. McEver
Structurally Distinct Requirements for Binding of P-selectin Glycoprotein Ligand-1 and Sialyl Lewis x to Anaplasma phagocytophilum and P-selectin
J. Biol. Chem., September 26, 2003; 278(39): 37987 - 37997.
[Abstract] [Full Text] [PDF]

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 BloodHome page
Y. Katayama, A. Hidalgo, B. C. Furie, D. Vestweber, B. Furie, and P. S. Frenette
PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: evidence for cooperation between E-selectin ligands and {alpha}4 integrin
Blood, September 15, 2003; 102(6): 2060 - 2067.
[Abstract] [Full Text] [PDF]

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 J. Leukoc. Biol.Home page
B. Walcheck, S. R. Alexander, C. A. St. Hill, and E. Matala
ADAM-17-independent shedding of L-selectin
J. Leukoc. Biol., September 1, 2003; 74(3): 389 - 394.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
H. Koyama, T. Maeno, S. Fukumoto, T. Shoji, T. Yamane, H. Yokoyama, M. Emoto, T. Shoji, H. Tahara, M. Inaba, et al.
Platelet P-Selectin Expression Is Associated With Atherosclerotic Wall Thickness in Carotid Artery in Humans
Circulation, August 5, 2003; 108(5): 524 - 529.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
C. B. Fieger, C. M. Sassetti, and S. D. Rosen
Endoglycan, a Member of the CD34 Family, Functions as an L-selectin Ligand through Modification with Tyrosine Sulfation and Sialyl Lewis x
J. Biol. Chem., July 25, 2003; 278(30): 27390 - 27398.
[Abstract] [Full Text] [PDF]

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 GlycobiologyHome page
D. J. Becker and J. B. Lowe
Fucose: biosynthesis and biological function in mammals
Glycobiology, July 1, 2003; 13(7): 41R - 53R.
[Abstract] [Full Text] [PDF]

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 JEMHome page
M. Sperandio, M. L. Smith, S. B. Forlow, T. S. Olson, L. Xia, R. P. McEver, and K. Ley
P-selectin Glycoprotein Ligand-1 Mediates L-Selectin-dependent Leukocyte Rolling in Venules
J. Exp. Med., May 19, 2003; 197(10): 1355 - 1363.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y. Levy, D. Ronen, A. D. Bershadsky, and Y. Zick
Sustained Induction of ERK, Protein Kinase B, and p70 S6 Kinase Regulates Cell Spreading and Formation of F-actin Microspikes Upon Ligation of Integrins by Galectin-8, a Mammalian Lectin
J. Biol. Chem., April 11, 2003; 278(16): 14533 - 14542.
[Abstract] [Full Text] [PDF]


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