Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand.

Bowen, Michael A.; Patel, Dhavalkumar D.; Li, X; Modrell, Brett; Malacko, Alison R.; Wang, W C; Marquardt, Hans; Neubauer, Michael; Pesando, John M.; Francke, Uta

doi:10.1084/jem.181.6.2213

Cited by 351 publications

(289 citation statements)

References 51 publications

(54 reference statements)

Supporting

Mentioning

280

Contrasting

Unclassified

Order By: Relevance

“…Two others members of this family have been identified in humans: basal-cell adhesion molecule and activated leukocytecell adhesion molecule, also called CD166 [2,3]. Basal-cell adhesion molecule is a splice variant of the Lutheran blood group glycoprotein that is reported to bind laminin [3].…”

Section: Introductionmentioning

confidence: 99%

“…NK cells Introduction CD146, also known as melanoma cell adhesion molecule (MCAM or Mel-CAM), MUC18, S-Endo1, A32 antigen, is an integral membrane glycoprotein of 113 kDa that belongs to the Ig superfamily with a characteristic V-V-C2-C2-C2 domain structure [1]. Two others members of this family have been identified in humans: basal-cell adhesion molecule and activated leukocytecell adhesion molecule, also called CD166 [2,3]. Basal-cell adhesion molecule is a splice variant of the Lutheran blood group glycoprotein that is reported to bind laminin [3].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mouse CD146/MCAM is a marker of natural killer cell maturation

et al. 2008

View full text Add to dashboard Cite

CD146/melanoma cell adhesion molecule is an adhesion molecule expressed by endothelial cells and by a small fraction of activated T and B lymphocytes in humans. In order to analyze the pattern of CD146 expression in mouse leukocytes at steady-state conditions, we generated a set of novel rat anti-mouse CD146 monoclonal antibodies. CD146 expression was undetectable on monocytes, dendritic cells, T cells or B cells, but was expressed on about 30% of neutrophils and 60% of NK cells. Within murine lymphocytes, CD146 was defined as a novel NK-specific surface molecule. An increased percentage of CD146 1 cells was found in the most mature CD27 À CD11b 1 NK cell subpopulation, which also displays higher expression of Ly49C/I, Ly49D and KLRG1 and lower expression of NKG2A/C/E molecules. CD146 1 NK cells were found to be less cytotoxic and produce less IFN-c than CD146 À NK cells upon stimulation with target cells or activating antibodies. These findings define CD146 as a marker of mouse NK cell maturation that may be used as an alternative to the combined use of CD27 and CD11b staining to detect final stages of NK cell maturation.Key words: Adhesion . Antibodies . CD146/MCAM . Maturation . NK cells Introduction CD146, also known as melanoma cell adhesion molecule (MCAM or Mel-CAM), MUC18, S-Endo1, A32 antigen, is an integral membrane glycoprotein of 113 kDa that belongs to the Ig superfamily with a characteristic V-V-C2-C2-C2 domain structure [1]. Two others members of this family have been identified in humans: basal-cell adhesion molecule and activated leukocytecell adhesion molecule, also called CD166 [2,3]. Basal-cell adhesion molecule is a splice variant of the Lutheran blood group glycoprotein that is reported to bind laminin [3]. Activated leukocyte-cell adhesion molecule is a costimulatory molecule mediating homophilic interaction and heterophilic interaction with CD6 and is involved in activation and trafficking of leukocytes into the central nervous system [4]. CD146 was originally defined as a marker of tumor progression and metastasis formation in human melanoma [5]. Overexpression of CD146 in CD146-negative melanoma cells renders these cells highly metastatic after injection in immunodeficient mice [6]. Moreover, injection of a humanized anti-CD146 mAb in immunodeficient mice bearing human melanomas significantly reduces the tumor size and the number of metastases [7]. The adhesive functions of CD146 were demonstrated using a solid-phase adhesion test in which both CD146-positive and CD146-negative melanoma cells bound to eucaryotic recombinant CD146 protein, suggesting that CD146 can mediate both homophilic and heterophilic interaction with an as yet unidentified ligand [8,9]. Using S-Endo1 mAb, we previously detected cell surface expression of CD146 on human vascular endothelial cells, whatever vessel caliber or anatomical region [10]. On cultured endothelial cells, CD146 is mainly located at the intercellular junctions and is involved in inter-endothelial cell adhesion and paracellular permeability [11,1...

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Mouse CD146/MCAM is a marker of natural killer cell maturation

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Initial identification of CD166 as a CD6L was accomplished by demonstrating that a mAb directed against a leukemia cell line, HPB-ALL, partially inhibited binding of soluble CD6-Ig fusion protein (CD6-Ig) to cultured thymic epithelial cells (12). In vitro, this mAb also reduced binding of thymocytes to thymic epithelial cells and homotypic binding of these epithelial cells (9), implying a role for interactions between CD6 and CD6L in thymocyte development. CD166 has been reported to be important in establishment of hemopoesis (13)(14)(15).…”

mentioning

confidence: 99%

“…CD166, also known as activated leukocyte cell adhesion molecule (ALCAM), is a 105-kDa Ig superfamily protein that binds to CD6, and is expressed by thymic epithelial cells, activated B and T cells, monocytes (8,9), melanoma cells (10), and mesenchymal stem cells (11). Initial identification of CD166 as a CD6L was accomplished by demonstrating that a mAb directed against a leukemia cell line, HPB-ALL, partially inhibited binding of soluble CD6-Ig fusion protein (CD6-Ig) to cultured thymic epithelial cells (12).…”

mentioning

confidence: 99%

Expression and Characterization of a Novel CD6 Ligand in Cells Derived from Joint and Epithelial Tissues

Saifullah

Fox

Sarkar

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

CD6 is a T cell surface glycoprotein that plays an important role in interactions of thymocytes with thymic epithelial cells and in mature T cell interactions with selected nonprofessional tissue APCs. We describe a novel CD6 ligand (CD6L) 3A11 Ag that is distinct from the known CD6L (CD166). The 3A11 protein is expressed on cells derived from human thymus, skin, synovium, and cartilage, and its expression is enhanced by IFN-γ. mAbs directed against the 3A11 Ag and CD166 exhibit distinct patterns of binding to a panel of cell lines. Confocal microscopy shows that both CD166 and the 3A11 Ag are expressed at the cell surface, and that these proteins colocalize. The 3A11 Ag has a molecular mass of 130 kDa and is immunoprecipitated using either mAb 3A11 or soluble CD6-Ig fusion protein. mAbs directed against individual CD6L were less potent than was soluble CD6-Ig fusion protein in reducing adhesion of T cells to adherent 3A11-positive epithelial cells in vitro, suggesting that these Abs recognize epitopes on the 3A11 Ag and CD166 that are distinct from CD6 binding sites. Finally, transfection of epithelial cells with CD166-specific small interfering RNAs significantly decreased CD166 expression without alteration in 3A11 Ag levels, and thus confirmed that these two CD6L are distinct. Taken together, our data identifies a novel 130-kDa CD6L that may mediate interactions of synovial and epithelial cells with T lymphocytes.

show abstract

“…The most membrane-proximal SRCR domain of CD6 is directly involved in the interaction with the CD6 ligand, CD166/activated leukocyte cell adhesion molecule (ALCAM) (5). CD166/ALCAM is found expressed on a great variety of cell types such as activated T and B lymphocytes, lymphomas, activated monocytes, keratinocytes, thymic epitelium, neurons, and brain cortex (6). Because both CD6 and CD166/ALCAM are expressed on thymocytes, the CD6-AL-CAM interaction has been implicated in thymocyte adhesion (6 -8) and thymocyte development (9).…”

mentioning

confidence: 99%

The Lymphocyte Receptor CD6 Interacts with Syntenin-1, a Scaffolding Protein Containing PDZ Domains

Gimferrer

Ibáñez

Farnós

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

CD6 is a type I membrane glycoprotein expressed on thymocytes, mature T and B1a lymphocytes, and CNS cells. CD6 binds to activated leukocyte cell adhesion molecule (CD166), and is considered as a costimulatory molecule involved in lymphocyte activation and thymocyte development. Accordingly, CD6 partially associates with the TCR/CD3 complex and colocalizes with it at the center of the mature immunological synapse (IS) on T lymphocytes. However, the signaling pathway used by CD6 is still mostly unknown. The yeast two-hybrid system has allowed us the identification of syntenin-1 as an interacting protein with the cytoplasmic tail of CD6. Syntenin-1 is a PDZ (postsynaptic density protein-95, postsynaptic discs large, and zona occludens-1) domain-containing protein, which functions as an adaptor protein able to bind cytoskeletal proteins and signal transduction effectors. Mutational analyses showed that certain amino acids of the most C-terminal sequence of CD6 (-YDDISAA) and the two postsynaptic density protein-95, postsynaptic discs large, and zona occludens-1 domains of syntenin-1 are relevant to the interaction. Further confirmation of the CD6-syntenin-1 interaction was obtained from pull-down and coimmunoprecipitation assays in mammalian cells. Image analyses also showed that syntenin-1 accumulates at CD6 caps and at the IS. Therefore, we propose that syntenin-1 may function as a scaffolding protein coupling CD6 and most likely other lymphocyte receptors to cytoskeleton and/or signaling effectors during IS maturation.

show abstract

Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand.

Cited by 351 publications

References 51 publications

Mouse CD146/MCAM is a marker of natural killer cell maturation

Mouse CD146/MCAM is a marker of natural killer cell maturation

Expression and Characterization of a Novel CD6 Ligand in Cells Derived from Joint and Epithelial Tissues

The Lymphocyte Receptor CD6 Interacts with Syntenin-1, a Scaffolding Protein Containing PDZ Domains

Contact Info

Product

Resources

About