Organization of the gene for human platelet/endothelial cell adhesion molecule-1 shows alternatively spliced isoforms and a functionally complex cytoplasmic domain

Nancy E. Kirschbaum, Richard J Gumina, Peter J. Newman

Research output: Contribution to journalArticle

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Abstract

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell-cell adhesion molecule that is expressed on circulating platelets, on leukocytes, and at the intercellular junctions of vascular endothelial cells and mediates the interactions of these cells during the process of transendothelial cell migration. The cDNA for PECAM-1 encodes an open reading frame of 738 amino acids (aa) that is organized into a 27-aa signal peptide, a 574-aa extracellular domain composed of 6 Ig homology units, and a relatively long cytoplasmic tail of 118 aa containing multiple sites for posttranslational modification and postreceptor signal transduction. To provide a molecular basis for the precise evaluation of the structure and function of this transmembrane glycoprotein, we have determined the organization of the human PECAM-1 gene. The PECAM-1 gene, which has been localized to human chromosome 17, is a single-copy gene of approximately 65 kb in length and is broken into 16 exons by introns ranging in size from 86 to greater than 12,000 bp in length. Typical of other members of the Ig superfamily, each of the extracellular Ig homology domains is encoded by a separate exon, consistent with PECAM-1 having arisen by gene duplication and exon shuffling of ancestral Ig superfamily genes. However, the cytoplasmic domain was found to be surprisingly complex, being encoded by seven short exons that may represent discrete functional entities. Alternative splicing of the cytoplasmic tail appears to generate multiple PECAM-1 isoforms that may regulate phosphorylation, cytoskeletal association, and affinity modulation of the mature protein. Finally, a processed pseudogene having 76% identity with PECAM-1 cDNA was identified and localized to human chromosome 3. These findings should have important implications for structure/function analysis of PECAM-1 and its role in vascular adhesive interactions.

Original languageEnglish (US)
Pages (from-to)4028-4037
Number of pages10
JournalBlood
Volume84
Issue number12
StatePublished - Dec 15 1994

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CD31 Antigens
Protein Isoforms
Genes
Exons
Amino Acids
Human Chromosomes
Chromosomes
Complementary DNA
Transendothelial and Transepithelial Migration
Signal transduction
Immunoglobulin Genes
Chromosomes, Human, Pair 17
Pseudogenes
Phosphorylation
Chromosomes, Human, Pair 3
Gene Duplication
Intercellular Junctions
human ESAM protein
Endothelial cells
Alternative Splicing

ASJC Scopus subject areas

  • Hematology

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Organization of the gene for human platelet/endothelial cell adhesion molecule-1 shows alternatively spliced isoforms and a functionally complex cytoplasmic domain. / Kirschbaum, Nancy E.; Gumina, Richard J; Newman, Peter J.

In: Blood, Vol. 84, No. 12, 15.12.1994, p. 4028-4037.

Research output: Contribution to journalArticle

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