1: Immunol Rev. 2002 Aug;186:19-36.


Glycosylation in the control of selectin counter-receptor structure and function.

Lowe JB.

Howard Hughes Medical Institute, Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109-0650, USA. JohnLowe@Umich.edu

Leukocyte trafficking is characterized by sequential cell adhesion and activation events that deliver specific leukocyte subsets to distinct extravascular locations under different pathophysiological circumstances. E-, P- and/or L-selectin-dependent leukocyte-endothelial cell adhesive interactions contribute essentially to this process. Selectin counter-receptor activity on leukocyte and high endothelial venules is borne by specific glycoproteins whose ability to support adhesion requires specific post-translational modifications. These modifications are typified by serine/threonine-linked oligosaccharides capped with the sialyl Lewis x moiety, an alpha2-3sialylated, alpha1-3ucosylated tetrasaccharide synthesized by specific glycosyltransferases. Recent advances in glycan structure analysis and in characterizing mice with targeted deletions of glycosyltransferase and sulfotransferase genes discloses an essential role for 6-O GlcNAc sulfate modification of the sialyl Lewis x tetrasaccharide in L-selectin counter-receptor activity. Related studies identify novel extended Core 1 type O-glycans bearing the 6-sulfosialyl Lewis x moiety, define the molecular nature of the MECA-79 epitope, and disclose a requirement for the alpha1-3fucosyltransferases FucT-IV and FucT-VII in the elaboration of L-selectin counter-receptor activities. Parallel studies also demonstrate that these 2 fucosyltransferases, a core 2 GlcNAc transferase, and core 2-type sialyl Lewis x determinants make essential contributions to leukocyte P-selectin counter-receptor activity, and figure prominently in the control of leukocyte E-selectin counter-receptor activity.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12234359 [PubMed - indexed for MEDLINE]

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2: Braz J Med Biol Res. 1999 May;32(5):519-28.


Structure and function of the selectin ligand PSGL-1.

Cummings RD.

Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA. richard-cummings@uokhsc.edu

P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric mucin-like 120-kDa glycoprotein on leukocyte surfaces that binds to P- and L-selectin and promotes cell adhesion in the inflammatory response. The extreme amino terminal extracellular domain of PSGL-1 is critical for these interactions, based on site-directed mutagenesis, blocking monoclonal antibodies, and biochemical analyses. The current hypothesis is that for high affinity interactions with P-selectin, PSGL-1 must contain O-glycans with a core-2 branched motif containing the sialyl Lewis x antigen (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta 1-->R). In addition, high affinity interactions require the co-expression of tyrosine sulfate on tyrosine residues near the critical O-glycan structure. This review addresses the biochemical evidence for this hypothesis and the evidence that PSGL-1 is an important in vivo ligand for cell adhesion.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 10412562 [PubMed - indexed for MEDLINE]

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3: Leuk Lymphoma. 1998 Mar;29(1-2):1-15.


Structure and function of P-selectin glycoprotein ligand-1.

Moore KL.

Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA. kevin-moore@ouhsc.edu

Directed emigration of leukocytes into inflammatory sites and lymphatic tissues is orchestrated by the regulated expression of adhesion and signaling molecules on cells within the vasculature. The selectin family of adhesion molecules that are expressed on activated endothelial cells (E-selectin and P-selectin), activated platelets (P-selectin), and peripheral blood leukocytes (L-selectin), mediate tethering and rolling of leukocytes to the vessel wall in the microcirculation. Selectins promote these interactions by binding to glycoconjugate ligands expressed on apposing cells. Selectin-mediated rolling is a prerequisite for firm adhesion and subsequent transendothelial migration of leukocytes into tissues. This review will focus on the structure and function of P-selectin glycoprotein ligand-1 (PSGL-1, CD162). PSGL-1 is a disulfide-bonded homodimeric mucin-like glycoprotein on leukocytes that interacts with P-, L-, and E-selectin. PSGL-1 mediates leukocyte-endothelial and leukocyte-platelet adhesion by binding to P-selectin expressed on activated endothelium and platelets and PSGL-1 mediates leukocyte-leukocyte adhesion by binding to L-selectin expressed on apposing leukocytes. PSGL-1 is unique in that it is the only selectin glycoprotein ligand that has been directly demonstrated to mediate cell-cell adhesion in vitro and in vivo.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 9638971 [PubMed - indexed for MEDLINE]

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4: Nippon Rinsho. 1995 Jul;53(7):1721-8.


[Structure and function of cell adhesion molecules in selectin family and their roles in cancer metastasis]

[Article in Japanese]

Kannagi R, Kawakami N, Narita T.

Laboratory of Experimental Pathology, Aichi Cancer Center, Research Institute.

Cell adhesion molecules of selectin family are involved in the metastasis of cancer at the step of attachment of cancer cells to endothelial cells. P-selectin mediated adhesion of cancer cells with platelets, and L-selectin mediated adhesion of leukocytes to cancer cells would also be involved in the process of hematogenous metastasis through the microthrombus formation. Upon adhesion to cancer cells, platelets and leukocytes secrete cytokines that induce E-selectin expression of endothelial cells, and this further facilitates hematogenous metastasis.

Publication Types:
English Abstract
Review

PMID: 7543164 [PubMed - indexed for MEDLINE]

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5: Structure. 1994 Mar 15;2(3):147-50.


Lectins on a roll: the structure of E-selectin.

Weis WI.

Department of Cell Biology, Stanford University School of Medicine, CA 94305.

The crystal structure of the lectin/EGF portion of E-selectin confirms anticipated similarities with homologous domains, but reveals some surprising features that emphasize the limitations of homology modelling.

Publication Types:
Comparative Study
Review

PMID: 7520818 [PubMed - indexed for MEDLINE]

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6: Rinsho Ketsueki. 1994 Mar;35(3):215-8.


[Structure and function of L-selectin]

[Article in Japanese]

Miyasaka M.

Department of Immunology, Tokyo Metropolitan Institute of Medical Science.

L-selectin, one of the selectin (LECAM) members, is thought to be the lymphocyte homing receptor that mediates binding of lymphocytes to high endothelial venules of peripheral lymph nodes. Although L-selectin is probably the most well-characterized lymphocyte adhesion molecule, there are still a number of unresolved issues, one of which is exact operating mechanism in the lymphocyte-HE cell interaction. This molecule is expressed not only by lymphocytes but also by all other types of leukocytes which in fact never recirculate in the body. We have cloned cDNA encoding rat L-selectin and produced a soluble fusion protein of rat L-selectin and human IgG, and used it to identify ligand structures recognized by L-selectin, and also to produce blocking as well as non-blocking monoclonal antibodies to rat L-selectin. By using these tools, we investigated the biological significance of interaction between L-selectin and its ligand. Summary of these results are presented herein.

Publication Types:
English Abstract
Review

PMID: 7512668 [PubMed - indexed for MEDLINE]

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7: Seikagaku. 1993 Mar;65(3):157-65.


[Structure and function of LECAM-1 (L-selectin)]

[Article in Japanese]

Miyasaka M, Tamatani T.

Department of Immunology, Tokyo Metropolitan Institute of Medical Science.

Publication Types:
Review

PMID: 7685804 [PubMed - indexed for MEDLINE]

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8: Bioessays. 1992 Dec;14(12):849-56.


The selectin family of carbohydrate-binding proteins: structure and importance of carbohydrate ligands for cell adhesion.

Cummings RD, Smith DF.

Dept. of Biochemistry and Molecular Biology, Oklahoma Center for Molecular Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73104.

Protein-carbohydrate interactions have been found to be important in many steps in lymphocyte recirculation and inflammatory responses. A family of carbohydrate-binding proteins or lectins, termed selectins, has been discovered and shown to be involved directly in these processes. The three known selectins, termed L-, E- and P-selectins, have domains homologous to other Ca(2+)-dependent (C-type) lectins. L-selectin is expressed constitutively on lymphocytes, E-selectin is expressed by activated endothelial cells, and P-selectin is expressed by activated platelets and endothelial cells. Here, we review the nature of the carbohydrate determinants in tissues recognized by these selectins. The expression of specific sialylated, fucosylated and sulfated carbohydrates in activated endothelium and high endothelial venules promotes interactions with L-selectin on leukocyte surfaces. In contrast, E- and P-selectins recognize specific carbohydrate determinants related to sialyl Le(x) antigen on neutrophil and monocyte surfaces. The discovery of the selectins has generated excitement among glycoconjugate researchers that other carbohydrate-binding proteins and their cognate ligands will be found to function in regulating many types of cellular interactions.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 1285423 [PubMed - indexed for MEDLINE]

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9: APMIS. 1992 Apr;100(4):287-93.


Structure and function of L-selectin.

Kansas GS.

Department of Pathology, Harvard Medical School, Boston, Massachusetts.

The selectins are a newly described family of carbohydrate-binding adhesion molecules involved in the regulation of leukocyte traffic. Selectins are composed of an N-terminal C-type lectin domain, a single EGF domain, a variable number of short consensus repeat (SCR) domains, a transmembrane region and a cytoplasmic tail. L-selectin (LAM-1/LECAM-1/LECCAM-1) is the only selectin expressed on leukocytes, and mediates a number of leukocyte-endothelial interactions, including the binding of lymphocytes to HEV of peripheral lymph node high endothelial venules (HEV), neutrophil rolling, and leukocyte attachment to cytokine-treated endothelium in vitro. Stable transfectants expressing a series of chimeric selectins and deletion mutants were functionally analyzed in order to determine the molecular basis of adhesion mediated by L-selectin. The specificity of adhesion was found to reside entirely within the lectin domain, suggesting that this domain is the only domain of the protein to interact with the carbohydrate ligand. These results make previous observations that certain mAbs which block function map to each of the extracellular domains difficult to interpret. In addition, deletion of the cytoplasmic tail of L-selectin abolished adhesion, without affecting ligand recognition. Thus, each domain of the selectins has an important, but distinct, role in cell adhesion.

Publication Types:
Review

PMID: 1374617 [PubMed - indexed for MEDLINE]