Alternative splicing of a specific cytoplasmic exon alters the binding characteristics of murine platelet/endothelial cell adhesion molecule-1 (PECAM-1).

Yan, H C; Baldwin, H S; Sun, J; Buck, C A; Albelda, S M; DeLisser, H M

Yan, H C; Baldwin, H S; Sun, J; Buck, C A; Albelda, S M; DeLisser, H M.

Afiliación

Yan HC; Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104-4283, USA.

J Biol Chem ; 270(40): 23672-80, 1995 Oct 06.

Article en En | MEDLINE | ID: mdl-7559536

RESUMEN

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a membrane glycoprotein expressed on endothelial cells, platelets, and leukocytes. Analysis of PECAM-1 expression in the developing mouse embryo has revealed the presence of multiple isoforms of murine PECAM-1 (muPECAM-1) that appeared to result from the alternative splicing of exons encoding cytoplasmic domain sequences (exons 10-16) (Baldwin, H. S., Shen, H. M., Yan, H., DeLisser, H. M., Chung, A., Mickanin, C., Trask, T., Kirschbaum, N. E. Newman, P. J., Albelda, S., and Buck, C. A. (1994) Development 120, 2539-2553). To investigate the functional consequences of alternatively spliced muPECAM-1 cytoplasmic domains, L-cells were transfected with cDNA for each variant and their ability to promote cell aggregation was compared. In this assay, full-length muPECAM-1 and all three isoforms containing exon 14 behaved like human PECAM-1 in that they mediated calcium- and heparin-dependent heterophilic aggregation. In contrast, three muPECAM-1 variants, all missing exon 14, mediated calcium- and heparin-independent homophilic aggregation. Exon 14 thus appears to modulate the ligand and adhesive interactions of the extracellular domain of PECAM-1. These findings suggest that alternative splicing may represent a mode of regulating the adhesive function of PECAM-1 in vivo and provides direct evidence that alternative splicing involving the cytoplasmic domain affects the ligand specificity and binding properties of a cell adhesion receptor.

Asunto(s)

Empalme Alternativo; Antígenos de Diferenciación Mielomonocítica/genética; Antígenos de Diferenciación Mielomonocítica/metabolismo; Moléculas de Adhesión Celular/genética; Moléculas de Adhesión Celular/metabolismo; Secuencia de Aminoácidos; Animales; Anticuerpos Monoclonales; Antígenos de Diferenciación Mielomonocítica/inmunología; Secuencia de Bases; Plaquetas/metabolismo; Moléculas de Adhesión Celular/inmunología; Agregación Celular; Clonación Molecular; Citoplasma/metabolismo; Cartilla de ADN/genética; ADN Complementario/genética; Embrión de Mamíferos; Endotelio Vascular/metabolismo; Exones; Variación Genética; Glicosilación; Humanos; Células L; Ligandos; Ratones; Datos de Secuencia Molecular; Molécula-1 de Adhesión Celular Endotelial de Plaqueta; Unión Proteica; Eliminación de Secuencia; Homología de Secuencia de Ácido Nucleico; Transfección

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Diferenciación Mielomonocítica / Moléculas de Adhesión Celular / Empalme Alternativo Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 1995 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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